MicroRNA Regulation in Cancer: Insights into Diagnosis, Prognosis, and Treatment
Main Article Content
Keywords
Oncogenesis, microRNA regulation, molecular mechanisms, prognostic biomarkers, therapeutic targets
Abstract
MicroRNAs (miRNAs) are tiny, non-coding RNA molecules that are pivotal in regulating cell growth, development, cell cycle, and programmed cell death. Alterations in miRNA expression, caused by various mechanisms such as amplification, deletion, mutation, or epigenetic changes, can lead to either an increase or decrease in their levels in cancerous cells. Since their initial discovery in 1993, a wealth of research has established miRNAs as key players in oncogenesis and tumor suppression across various human cancers. The study of miRNAs is critical for predicting cancer outcomes and aiding in its detection. Numerous miRNAs have demonstrated potential as markers for cancer prognosis and diagnosis, as well as targets for therapy. Their profound influence on tumor development and spread is becoming increasingly acknowledged. This article presents a summary of how miRNAs are synthesized and generated, and explores their dual function as tumor suppressors and oncogenes. Additionally, we delve into the promising applications of miRNAs as instruments for cancer diagnosis, prognosis assessment, and therapeutic intervention.
References
REFERENCES
1. Khan A, Zhang X. Function of the long noncoding RNAs in hepatocellular carcinoma: Classification, molecular mechanisms, and significant therapeutic potentials. Bioengineering. 2022;9(8):406.
2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33.
3. Da C-m, Gong C-Y, Nan W, Zhou K-S, Zuo-Long W, Zhang H-H. The role of long non-coding RNA MIAT in cancers. Biomedicine & Pharmacotherapy. 2020;129:110359.
4. Han C, Yu Z, Duan Z, Kan Q. Role of microRNA-1 in human cancer and its therapeutic potentials. BioMed Research International. 2014;2014:1–9.
5. Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends in Molecular Medicine. 2014;20(8):460–469.
6. Dvinge H, Git A, Gräf S, Salmon-Divon M, Curtis C, Sottoriva A, et al. The shaping and functional consequences of the microRNA landscape in breast cancer. Nature. 2013;497(7449):378–382.
7. Manterola L, Guruceaga E, Pérez-Larraya JG, González-Huarriz M, Jauregui P, Tejada S, et al. A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool. Neuro-Oncology. 2014;16(4):520–527.
8. Peng Y, Croce CM. The role of microRNAs in human cancer. Signal Transduction and Targeted Therapy. 2016;1(1).
9. Zhang L, Liao Y, Tang L. MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer. Journal of Experimental & Clinical Cancer Research. 2019;38(1).
10. Mardani R, Abadi MHJN, Motieian M, Taghizadeh-Boroujeni S, Bayat A, Farsinezhad A, et al. MicroRNA in leukemia: tumor suppressors and oncogenes with prognostic potential. Journal of Cellular Physiology. 2018;234(6):8465–8486.
11. Long Z, Wang Y. miR-195-5p suppresses lung cancer cell proliferation, migration, and invasion via FOXK1. Technology in Cancer Research & Treatment. 2020;19:153303382092258.
12. Hamam SM, Abdelzaher E, Fadel S, Nassra RA, Sharafeldin HA. Prognostic value of microRNA-125a expression status in molecular groups of pediatric medulloblastoma. Child’s Nervous System. 2023;39(7):1869–1880.
13. Yu X, Zheng H, Sun R, Qian X-J, Jiang P, Yang B, et al. MicroRNA-425-5p inhibits lung cancer cell growth in vitro and in vivo by downregulating TFIIB-related factor 2. Technology in Cancer Research & Treatment. 2020;19:153303381990111.
14. Ai N, Li B, Li L, Li Z, Ji H, Yang G, et al. MicroRNA-466 inhibits cancer cell migration and invasion in hepatocellular carcinoma by indirectly mediating the downregulation of ROCK2. Experimental and Therapeutic Medicine. 2019.
15. Chen L, Bourguignon LYW. Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to BCL-2 expression and chemoresistance in breast cancer cells. Molecular Cancer. 2014;13(1):52.
16. Jacob H, Stanisavljevic L, Storli KE, Hestetun KE, Dahl O, Myklebust MP. A four-microRNA classifier as a novel prognostic marker for tumor recurrence in stage II colon cancer. Scientific Reports. 2018;8(1).
17. Stahlhut C, Slack FJ. MicroRNAs and the cancer phenotype: profiling, signatures and clinical implications. Genome Medicine. 2013;5(12):1–12.
18. Sun Y-F, Leu J-D, Chen S-M, Lin I, Lee Y-J. Results based on 124 cases of breast cancer and 97 controls from Taiwan suggest that the SNP309 in the MDM2 gene promoter is associated with earlier onset and increased risk of breast cancer. BMC Cancer. 2009;9(1):1–7.
19. de Leeuw DC, van den Ancker W, Denkers F, de Menezes RX, Westers TM, Ossenkoppele GJ, et al. MicroRNA profiling can classify acute leukemias of ambiguous lineage as either acute myeloid leukemia or acute lymphoid leukemia. Clinical Cancer Research. 2013;19(8):2187–2196.
20. Tan W, Liu B, Qu S, Liang G, Luo W, Gong C. MicroRNAs and cancer: key paradigms in molecular therapy. Oncology Letters. 2018;15(3):2735–2742.
21. Antolín S, Calvo L, Blanco-Calvo M, Santiago MP, Lorenzo-Patiño MJ, Haz-Conde M, et al. Circulating miR-200c and miR-141 and outcomes in patients with breast cancer. BMC Cancer. 2015;15(1):1–15.
22. Zanutto S, Pizzamiglio S, Ghilotti M, Bertan C, Ravagnani F, Perrone F, et al. Circulating miR-378 in plasma: a reliable, haemolysis-independent biomarker for colorectal cancer. British Journal of Cancer. 2014;110(4):1001–1007.
23. Zhang J, Song Y, Zhang C, Zhi X, Fu H, Ma Y, et al. Circulating miR-16-5p and miR-19b-3p as two novel potential biomarkers to indicate progression of gastric cancer. Theranostics. 2015;5(7):733.
24. Zhao Y, Song Y, Yao L, Song G, Teng C. Circulating microRNAs: promising biomarkers involved in several cancers and other diseases. DNA and Cell Biology. 2017;36(2):77–94.
25. Kawaguchi T, Komatsu S, Ichikawa D, Morimura R, Tsujiura M, Konishi H, et al. Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer. British Journal of Cancer. 2013;108(2):361–369.
26. Reza Mirzaei H, Sahebkar A, Mohammadi M, Yari R, Salehi H, Hasan Jafari M, et al. Circulating microRNAs in hepatocellular carcinoma: potential diagnostic and prognostic biomarkers. Current Pharmaceutical Design. 2016;22(34):5257–5269.
27. Zedan AH, Hansen TF, Assenholt J, Pleckaitis M, Madsen JS, Osther PJS. microRNA expression in tumour tissue and plasma in patients with newly diagnosed metastatic prostate cancer. Tumour Biology. 2018;40(5):1010428318775864.
28. Zhang N, Hu X, Du Y, Du J. The role of miRNAs in colorectal cancer progression and chemoradiotherapy. Biomedicine & Pharmacotherapy. 2021;134:111099.
29. Tian L, Shan W, Zhang Y, Lv X, Li X, Wei C. Up-regulation of miR-21 expression predicate advanced clinicopathological features and poor prognosis in patients with non-small cell lung cancer. Pathology Oncology Research. 2016;22(1):161–167.
30. Kumar S, Sharawat SK, Ali A, Gaur V, Malik PS, Kumar S, et al. Identification of differentially expressed circulating serum microRNA for the diagnosis and prognosis of Indian non-small cell lung cancer patients. Current Problems in Cancer. 2020;44(4):100540.
31. Adhami M, Haghdoost AA, Sadeghi B, Malekpour Afshar R. Candidate miRNAs in human breast cancer biomarkers: a systematic review. Breast Cancer (Tokyo). 2018;25(2):198–205.
32. Kadera BE, Li L, Toste PA, Wu N, Adams C, Dawson DW, et al. MicroRNA-21 in pancreatic ductal adenocarcinoma tumor-associated fibroblasts promotes metastasis. PLoS One. 2013;8(8):e71978.
33. Valeri N, Gasparini P, Braconi C, Paone A, Lovat F, Fabbri M, et al. MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2. Proceedings of the National Academy of Sciences. 2010;107(49):21098–21103.
34. Ma J, Dong C, Ji C. MicroRNA and drug resistance. Cancer Gene Therapy. 2010;17(8):523–531.
35. Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S, et al. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. Journal of Pathology. 2005;207(2):243–249.
36. Tam W, Hughes SH, Hayward WS, Besmer P. Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis. Journal of Virology. 2002;76(9):4275–4286.
37. Singh R, Mo Y-Y. Role of microRNAs in breast cancer. Cancer Biology & Therapy. 2013;14(3):201–212.
38. Loh HY, Norman BP, Lai KS, Rahman N, Alitheen NBM, Osman MA. The regulatory role of microRNAs in breast cancer. International Journal of Molecular Sciences. 2019;20(19).
39. Chen CZ. MicroRNAs as oncogenes and tumor suppressors. New England Journal of Medicine. 2005;353(17):1768–1771.
40. Durán-Sanchón S, Moreno L, Augé JM, Serra-Burriel M, Cuatrecasas M, Moreira L, et al. Identification and validation of microRNA profiles in fecal samples for detection of colorectal cancer. Gastroenterology. 2020;158(4):947–957.e4.
41. Guan H, Li W, Li Y, Wang J, Li Y, Tang Y, et al. MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2. PLoS One. 2017;12(12):e0189490.
42. Chen S, Zhang Y, Ding X, Li W. Identification of lncRNA/circRNA-miRNA-mRNA ceRNA network as biomarkers for hepatocellular carcinoma. Frontiers in Genetics. 2022;13:538.
43. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–854.
44. Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nucleic Acids Research. 2008;36(Database Issue):D154–D158.
45. Olena AF, Patton JG. Genomic organization of microRNAs. Journal of Cellular Physiology. 2010;222(3):540–545.
46. Ha M, Kim VN. Regulation of microRNA biogenesis. Nature Reviews Molecular Cell Biology. 2014;15(8):509–524.
47. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nature Cell Biology. 2009;11(3):228–234.
48. Friedman RC, Farh KKH, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Research. 2009;19(1):92–105.
49. Hong DS, Kang YK, Borad M, Sachdev J, Ejadi S, Lim HY, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. British Journal of Cancer. 2020;122(11):1630–1637.
50. Cortez MA, Ivan C, Valdecanas D, Wang X, Peltier HJ, Ye Y, et al. PDL1 regulation by p53 via miR-34. Journal of the National Cancer Institute. 2016;108(1).
REFERENCES
51. Lujambio A, Lowe SW. The microcosmos of cancer. Nature. 2012;482(7385):347–355.
52. Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annual Review of Medicine. 2009;60:167–179.
53. Esquela-Kerscher A, Slack FJ. Oncomirs – microRNAs with a role in cancer. Nature Reviews Cancer. 2006;6(4):259–269.
54. Mendell JT. MicroRNAs: critical regulators of development, cellular physiology and malignancy. Cell Cycle. 2005;4(9):1179–1184.
55. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–838.
56. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences. 2006;103(7):2257–2261.
57. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Research. 2005;65(16):7065–7070.
58. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences. 2002;99(24):15524–15529.
59. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences. 2004;101(9):2999–3004.
60. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435(7043):828–833.
61. O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc–regulated microRNAs modulate E2F1 expression. Nature. 2005;435(7043):839–843.
62. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. RAS is regulated by the let-7 microRNA family. Cell. 2005;120(5):635–647.
63. Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proceedings of the National Academy of Sciences. 2008;105(10):3903–3908.
64. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self-renewal and tumorigenicity of breast cancer cells. Cell. 2007;131(6):1109–1123.
65. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences. 2005;102(39):13944–13949.
66. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, et al. Targeted deletion reveals essential and overlapping functions of the miR-17~92 family of miRNA clusters. Cell. 2008;132(5):875–886.
67. Olive V, Jiang I, He L. mir-17-92, a cluster of miRNAs in the midst of the cancer network. International Journal of Biochemistry & Cell Biology. 2010;42(8):1348–1354.
68. Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21–induced pre-B-cell lymphoma. Nature. 2010;467(7311):86–90.
69. Hatley ME, Patrick DM, Garcia MR, Richardson JA, Bassel-Duby R, van Rooij E, et al. Modulation of K-Ras–dependent lung tumorigenesis by microRNA-21. Cancer Cell. 2010;18(3):282–293.
70. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Research. 2005;65(14):6029–6033.
71. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. Journal of Biological Chemistry. 2008;283(2):1026–1033.
72. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Research. 2008;18(3):350–359.
73. Selcuklu SD, Donoghue MTA, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochemical Society Transactions. 2009;37(4):918–925.
74. Wang Z, Li Y, Kong D, Sarkar FH. The role of microRNAs in epithelial-mesenchymal transition induced by transforming growth factor-β in cancer. Journal of Cellular and Molecular Medicine. 2010;14(10):2343–2354.
75. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology. 2008;10(5):593–601.
76. Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. Journal of Biological Chemistry. 2008;283(22):14910–14914.
77. Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Research. 2008;68(19):7846–7854.
78. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes & Development. 2008;22(7):894–907.
79. Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Reports. 2008;9(6):582–589.
80. Gibbons DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, et al. Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes & Development. 2009;23(18):2140–2151.
81. Brabletz S, Brabletz T. The ZEB/miR-200 feedback loop – a motor of cellular plasticity in development and cancer? EMBO Reports. 2010;11(9):670–677.
82. Schliekelman MJ, Gibbons DL, Faca VM, Creighton CJ, Rizvi ZH, Zhang Q, et al. Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer. Cancer Research. 2011;71(24):7670–7682.
83. Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK. MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Molecular Cancer Therapeutics. 2009;8(5):1055–1066.
84. Howe EN, Cochrane DR, Richer JK. The miR-200 and miR-221/222 microRNA families: opposing effects on epithelial identity. Journal of Mammary Gland Biology and Neoplasia. 2012;17(1):65–77.
85. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449(7163):682–688.
86. Gee HE, Camps C, Buffa FM, Colella S, Sheldon H, Gleadle JM, et al. MicroRNA-10b and breast cancer metastasis. Nature. 2008;455(7216):919–922.
87. Hurst DR, Edmonds MD, Welch DR. Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Research. 2009;69(19):7495–7498.
88. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nature Cell Biology. 2008;10(2):202–210.
89. Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451(7175):147–152.
90. Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC, et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009;137(6):1032–1046.
91. Zhang J, Yang J, Zhan Y, Shi H, Huang J, Jin M, et al. MicroRNA-196a promotes an aggressive phenotype in colorectal cancer via regulation of HOXB7. Molecular Cancer. 2014;13:48.
92. Hou J, Lin L, Zhou W, Wang Z, Ding G, Dong Q, et al. Identification of miR-151 as a metastasis-promoting microRNA in hepatocellular carcinoma. Cancer Research. 2011;71(7):2450–2459.
93. Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proceedings of the National Academy of Sciences. 2008;105(36):13556–13561.
94. Khew-Goodall Y, Goodall GJ. Myc-modulated miR-9 makes E-cadherin a target for metastasis. Nature Cell Biology. 2010;12(10):101–112.
95. Sun Y, Fang R, Li C, Li L, Li F, Ye X, et al. Hsa-miR-155 promotes gastric cancer growth and invasion by regulating SOCS1. Cancer Research. 2014;74(17):4905–4915.
96. Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, et al. MicroRNA-155 functions as an oncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Research. 2010;70(8):3119–3127.
97. Wang B, Li J, Sun M, Sun L, Zhang X. miR-155 promotes gastric cancer cell proliferation by targeting FOXO3a. Oncology Reports. 2016;36(4):2115–2123.
98. O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nature Reviews Immunology. 2010;10(2):111–122.
99. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-α stimulation and their possible roles in regulating the response to endotoxin shock. Journal of Immunology. 2007;179(8):5082–5089.
100. Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N, et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice. Proceedings of the National Academy of Sciences. 2006;103(18):7024–7029.REFERENCES
101. Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA. 2005;102(10):3627–3632.
102. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA. 2007;104(40):15805–15810.
103. Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CEA, Callegari E, et al. MicroRNA-29b induces global DNA hypomethylation in acute myeloid leukemia by targeting DNA methyltransferases. Proc Natl Acad Sci USA. 2009;106(34):13544–13549.
104. Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, et al. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008;68(11):4123–4132.
105. Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Körner H, et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle. 2008;7(16):2591–2600.
106. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447(7148):1130–1134.
107. Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26(5):745–752.
108. Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007;26(5):731–743.
109. Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007;17(15):1298–1307.
110. Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010;17(2):193–199.
111. Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY. MicroRNA-34b and microRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 2007;67(18):8433–8438.
112. Wang LG, Gu J. p53-dependent transcriptional regulation of miR-34 family. Cell Cycle. 2011;10(12):1847–1848.
113. Siemens H, Jackstadt R, Hünten S, Kaller M, Menssen A, Götz U, et al. miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle. 2011;10(24):4256–4271.
114. Kim NH, Kim HS, Li XY, Lee I, Choi HS, Kang SE, et al. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial–mesenchymal transition. J Cell Biol. 2011;195(3):417–433.
115. Li N, Fu H, Tie Y, Hu Z, Kong W, Wu Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275(1):44–53.
116. Migliore C, Petrelli A, Ghiso E, Corso S, Capparuccia L, Eramo A, et al. MicroRNAs impair MET-mediated invasive growth. Cancer Res. 2008;68(24):10128–10136.
117. Siemens H, Jackstadt R, Hünten S, Kaller M, Menssen A, Götz U, et al. miR-34 regulates Wnt signaling and suppresses colorectal cancer metastasis. Cancer Res. 2011;71(24):1–10.
118. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids—the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011;8(8):467–477.
119. Etheridge A, Lee I, Hood L, Galas D, Wang K. Extracellular microRNA: a new source of biomarkers. Mutat Res. 2011;717(1–2):85–90.
120. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–659.
121. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470–1476.
122. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13–21.
123. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101(10):2087–2092.
124. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105(30):10513–10518.
125. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006.
126. Schwarzenbach H, Nishida N, Calin GA, Pantel K. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014;11(3):145–156.
127. Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011;39(16):7223–7233.
128. Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA. 2011;108(12):5003–5008.
129. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011;13(4):423–433.
130. Chen X, Liang H, Zhang J, Zen K, Zhang CY. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol. 2012;22(3):125–132.
131. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Competitive interactions of cancer cells and normal cells via secretory microRNAs. J Biol Chem. 2012;287(2):1397–1405.
132. Mittelbrunn M, Gutiérrez-Vázquez C, Villarroya-Beltri C, González S, Sánchez-Cabo F, González MÁ, et al. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun. 2011;2:282.
133. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MAJ, Hopmans ES, Lindenberg JL, et al. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA. 2010;107(14):6328–6333.
134. Squadrito ML, Baer C, Burdet F, Maderna C, Gilfillan GD, Lyle R, et al. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep. 2014;8(5):1432–1446.
135. Villarroya-Beltri C, Baixauli F, Gutiérrez-Vázquez C, Sánchez-Madrid F, Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin Cancer Biol. 2014;28:3–13.
136. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–289.
137. Yáñez-Mó M, Siljander PRM, Andreu Z, Zavec AB, Borràs FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.
138. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2(8):569–579.
139. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478).
140. O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol. 2020;21(10):585–606.
141. Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226–1232.
142. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–383.
143. Mathieu M, Martin-Jaular L, Lavieu G, Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9–17.
144. Alix-Panabières C, Pantel K. Liquid biopsy: from discovery to clinical application. Cancer Discov. 2021;11(4):858–873.
145. Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20(2):71–88.
146. Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223–238.
147. Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol. 2017;14(9):531–548.
148. Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic—implementation issues and future challenges. Nat Rev Clin Oncol. 2021;18(5):297–312.
149. Merker JD, Oxnard GR, Compton C, Diehn M, Hurley P, Lazar AJ, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;36(16):1631–1641.
150. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10(8):472–484.
151. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.
152. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–990.
153. Dawson SJ, Tsui DWY, Murtaza M, Biggs H, Rueda OM, Chin SF, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–1209.
154. Murtaza M, Dawson SJ, Tsui DWY, Gale D, Forshew T, Piskorz AM, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013;497(7447):108–112.
155. Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017;545(7655):446–451.
156. Wan JCM, Heider K, Gale D, Murphy S, Fisher E, Mouliere F, et al. ctDNA monitoring using patient-specific sequencing and integration of variant reads. Sci Transl Med. 2020;12(548).
157. Cristiano S, Leal A, Phallen J, Fiksel J, Adleff V, Bruhm DC, et al. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature. 2019;570(7761):385–389.
158. Mouliere F, Chandrananda D, Piskorz AM, Moore EK, Morris J, Ahlborn LB, et al. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci Transl Med. 2018;10(466).
159. Abbosh C, Swanton C, Birkbak NJ. Clonal haematopoiesis: a source of biological noise in cell-free DNA analyses. Ann Oncol. 2019;30(3):358–359.
160. Razavi P, Li BT, Brown DN, Jung B, Hubbell E, Shen R, et al. High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat Med. 2019;25(12):1928–1937.
161. Merker JD, Oxnard GR, Compton C, Diehn M, Hurley P, Lazar AJ, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;36(16):1631–1641.
162. S. Shamsizadeh, S. Goliaei, CAMIRADA: Cancer microRNA Association Discovery Algorithm, a Case Study on Breast Cancer,
Journal of Biomedical Informatics 94 (2019) 103180.
163. A.R. Halvorsen, Å. Helland, P. Gromov, V.T. Wielenga, M.-L.M. Talman, N. Brünner, V. Sandhu, A.L. Børresen‐Dale, I. Gromova,
V.D. Haakensen, Profiling of MicroRNA s in Tumor Interstitial Fluid of Breast Tumors – A Novel Resource to Identify
Biomarkers for Prognostic Classification and Detection of Cancer, Molecular Oncology 11(2) (2016) 220-234.
1. Khan A, Zhang X. Function of the long noncoding RNAs in hepatocellular carcinoma: Classification, molecular mechanisms, and significant therapeutic potentials. Bioengineering. 2022;9(8):406.
2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33.
3. Da C-m, Gong C-Y, Nan W, Zhou K-S, Zuo-Long W, Zhang H-H. The role of long non-coding RNA MIAT in cancers. Biomedicine & Pharmacotherapy. 2020;129:110359.
4. Han C, Yu Z, Duan Z, Kan Q. Role of microRNA-1 in human cancer and its therapeutic potentials. BioMed Research International. 2014;2014:1–9.
5. Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends in Molecular Medicine. 2014;20(8):460–469.
6. Dvinge H, Git A, Gräf S, Salmon-Divon M, Curtis C, Sottoriva A, et al. The shaping and functional consequences of the microRNA landscape in breast cancer. Nature. 2013;497(7449):378–382.
7. Manterola L, Guruceaga E, Pérez-Larraya JG, González-Huarriz M, Jauregui P, Tejada S, et al. A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool. Neuro-Oncology. 2014;16(4):520–527.
8. Peng Y, Croce CM. The role of microRNAs in human cancer. Signal Transduction and Targeted Therapy. 2016;1(1).
9. Zhang L, Liao Y, Tang L. MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer. Journal of Experimental & Clinical Cancer Research. 2019;38(1).
10. Mardani R, Abadi MHJN, Motieian M, Taghizadeh-Boroujeni S, Bayat A, Farsinezhad A, et al. MicroRNA in leukemia: tumor suppressors and oncogenes with prognostic potential. Journal of Cellular Physiology. 2018;234(6):8465–8486.
11. Long Z, Wang Y. miR-195-5p suppresses lung cancer cell proliferation, migration, and invasion via FOXK1. Technology in Cancer Research & Treatment. 2020;19:153303382092258.
12. Hamam SM, Abdelzaher E, Fadel S, Nassra RA, Sharafeldin HA. Prognostic value of microRNA-125a expression status in molecular groups of pediatric medulloblastoma. Child’s Nervous System. 2023;39(7):1869–1880.
13. Yu X, Zheng H, Sun R, Qian X-J, Jiang P, Yang B, et al. MicroRNA-425-5p inhibits lung cancer cell growth in vitro and in vivo by downregulating TFIIB-related factor 2. Technology in Cancer Research & Treatment. 2020;19:153303381990111.
14. Ai N, Li B, Li L, Li Z, Ji H, Yang G, et al. MicroRNA-466 inhibits cancer cell migration and invasion in hepatocellular carcinoma by indirectly mediating the downregulation of ROCK2. Experimental and Therapeutic Medicine. 2019.
15. Chen L, Bourguignon LYW. Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to BCL-2 expression and chemoresistance in breast cancer cells. Molecular Cancer. 2014;13(1):52.
16. Jacob H, Stanisavljevic L, Storli KE, Hestetun KE, Dahl O, Myklebust MP. A four-microRNA classifier as a novel prognostic marker for tumor recurrence in stage II colon cancer. Scientific Reports. 2018;8(1).
17. Stahlhut C, Slack FJ. MicroRNAs and the cancer phenotype: profiling, signatures and clinical implications. Genome Medicine. 2013;5(12):1–12.
18. Sun Y-F, Leu J-D, Chen S-M, Lin I, Lee Y-J. Results based on 124 cases of breast cancer and 97 controls from Taiwan suggest that the SNP309 in the MDM2 gene promoter is associated with earlier onset and increased risk of breast cancer. BMC Cancer. 2009;9(1):1–7.
19. de Leeuw DC, van den Ancker W, Denkers F, de Menezes RX, Westers TM, Ossenkoppele GJ, et al. MicroRNA profiling can classify acute leukemias of ambiguous lineage as either acute myeloid leukemia or acute lymphoid leukemia. Clinical Cancer Research. 2013;19(8):2187–2196.
20. Tan W, Liu B, Qu S, Liang G, Luo W, Gong C. MicroRNAs and cancer: key paradigms in molecular therapy. Oncology Letters. 2018;15(3):2735–2742.
21. Antolín S, Calvo L, Blanco-Calvo M, Santiago MP, Lorenzo-Patiño MJ, Haz-Conde M, et al. Circulating miR-200c and miR-141 and outcomes in patients with breast cancer. BMC Cancer. 2015;15(1):1–15.
22. Zanutto S, Pizzamiglio S, Ghilotti M, Bertan C, Ravagnani F, Perrone F, et al. Circulating miR-378 in plasma: a reliable, haemolysis-independent biomarker for colorectal cancer. British Journal of Cancer. 2014;110(4):1001–1007.
23. Zhang J, Song Y, Zhang C, Zhi X, Fu H, Ma Y, et al. Circulating miR-16-5p and miR-19b-3p as two novel potential biomarkers to indicate progression of gastric cancer. Theranostics. 2015;5(7):733.
24. Zhao Y, Song Y, Yao L, Song G, Teng C. Circulating microRNAs: promising biomarkers involved in several cancers and other diseases. DNA and Cell Biology. 2017;36(2):77–94.
25. Kawaguchi T, Komatsu S, Ichikawa D, Morimura R, Tsujiura M, Konishi H, et al. Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer. British Journal of Cancer. 2013;108(2):361–369.
26. Reza Mirzaei H, Sahebkar A, Mohammadi M, Yari R, Salehi H, Hasan Jafari M, et al. Circulating microRNAs in hepatocellular carcinoma: potential diagnostic and prognostic biomarkers. Current Pharmaceutical Design. 2016;22(34):5257–5269.
27. Zedan AH, Hansen TF, Assenholt J, Pleckaitis M, Madsen JS, Osther PJS. microRNA expression in tumour tissue and plasma in patients with newly diagnosed metastatic prostate cancer. Tumour Biology. 2018;40(5):1010428318775864.
28. Zhang N, Hu X, Du Y, Du J. The role of miRNAs in colorectal cancer progression and chemoradiotherapy. Biomedicine & Pharmacotherapy. 2021;134:111099.
29. Tian L, Shan W, Zhang Y, Lv X, Li X, Wei C. Up-regulation of miR-21 expression predicate advanced clinicopathological features and poor prognosis in patients with non-small cell lung cancer. Pathology Oncology Research. 2016;22(1):161–167.
30. Kumar S, Sharawat SK, Ali A, Gaur V, Malik PS, Kumar S, et al. Identification of differentially expressed circulating serum microRNA for the diagnosis and prognosis of Indian non-small cell lung cancer patients. Current Problems in Cancer. 2020;44(4):100540.
31. Adhami M, Haghdoost AA, Sadeghi B, Malekpour Afshar R. Candidate miRNAs in human breast cancer biomarkers: a systematic review. Breast Cancer (Tokyo). 2018;25(2):198–205.
32. Kadera BE, Li L, Toste PA, Wu N, Adams C, Dawson DW, et al. MicroRNA-21 in pancreatic ductal adenocarcinoma tumor-associated fibroblasts promotes metastasis. PLoS One. 2013;8(8):e71978.
33. Valeri N, Gasparini P, Braconi C, Paone A, Lovat F, Fabbri M, et al. MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2. Proceedings of the National Academy of Sciences. 2010;107(49):21098–21103.
34. Ma J, Dong C, Ji C. MicroRNA and drug resistance. Cancer Gene Therapy. 2010;17(8):523–531.
35. Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S, et al. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. Journal of Pathology. 2005;207(2):243–249.
36. Tam W, Hughes SH, Hayward WS, Besmer P. Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis. Journal of Virology. 2002;76(9):4275–4286.
37. Singh R, Mo Y-Y. Role of microRNAs in breast cancer. Cancer Biology & Therapy. 2013;14(3):201–212.
38. Loh HY, Norman BP, Lai KS, Rahman N, Alitheen NBM, Osman MA. The regulatory role of microRNAs in breast cancer. International Journal of Molecular Sciences. 2019;20(19).
39. Chen CZ. MicroRNAs as oncogenes and tumor suppressors. New England Journal of Medicine. 2005;353(17):1768–1771.
40. Durán-Sanchón S, Moreno L, Augé JM, Serra-Burriel M, Cuatrecasas M, Moreira L, et al. Identification and validation of microRNA profiles in fecal samples for detection of colorectal cancer. Gastroenterology. 2020;158(4):947–957.e4.
41. Guan H, Li W, Li Y, Wang J, Li Y, Tang Y, et al. MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2. PLoS One. 2017;12(12):e0189490.
42. Chen S, Zhang Y, Ding X, Li W. Identification of lncRNA/circRNA-miRNA-mRNA ceRNA network as biomarkers for hepatocellular carcinoma. Frontiers in Genetics. 2022;13:538.
43. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–854.
44. Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nucleic Acids Research. 2008;36(Database Issue):D154–D158.
45. Olena AF, Patton JG. Genomic organization of microRNAs. Journal of Cellular Physiology. 2010;222(3):540–545.
46. Ha M, Kim VN. Regulation of microRNA biogenesis. Nature Reviews Molecular Cell Biology. 2014;15(8):509–524.
47. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nature Cell Biology. 2009;11(3):228–234.
48. Friedman RC, Farh KKH, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Research. 2009;19(1):92–105.
49. Hong DS, Kang YK, Borad M, Sachdev J, Ejadi S, Lim HY, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. British Journal of Cancer. 2020;122(11):1630–1637.
50. Cortez MA, Ivan C, Valdecanas D, Wang X, Peltier HJ, Ye Y, et al. PDL1 regulation by p53 via miR-34. Journal of the National Cancer Institute. 2016;108(1).
REFERENCES
51. Lujambio A, Lowe SW. The microcosmos of cancer. Nature. 2012;482(7385):347–355.
52. Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annual Review of Medicine. 2009;60:167–179.
53. Esquela-Kerscher A, Slack FJ. Oncomirs – microRNAs with a role in cancer. Nature Reviews Cancer. 2006;6(4):259–269.
54. Mendell JT. MicroRNAs: critical regulators of development, cellular physiology and malignancy. Cell Cycle. 2005;4(9):1179–1184.
55. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–838.
56. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences. 2006;103(7):2257–2261.
57. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Research. 2005;65(16):7065–7070.
58. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences. 2002;99(24):15524–15529.
59. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences. 2004;101(9):2999–3004.
60. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435(7043):828–833.
61. O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc–regulated microRNAs modulate E2F1 expression. Nature. 2005;435(7043):839–843.
62. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. RAS is regulated by the let-7 microRNA family. Cell. 2005;120(5):635–647.
63. Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proceedings of the National Academy of Sciences. 2008;105(10):3903–3908.
64. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self-renewal and tumorigenicity of breast cancer cells. Cell. 2007;131(6):1109–1123.
65. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences. 2005;102(39):13944–13949.
66. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, et al. Targeted deletion reveals essential and overlapping functions of the miR-17~92 family of miRNA clusters. Cell. 2008;132(5):875–886.
67. Olive V, Jiang I, He L. mir-17-92, a cluster of miRNAs in the midst of the cancer network. International Journal of Biochemistry & Cell Biology. 2010;42(8):1348–1354.
68. Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21–induced pre-B-cell lymphoma. Nature. 2010;467(7311):86–90.
69. Hatley ME, Patrick DM, Garcia MR, Richardson JA, Bassel-Duby R, van Rooij E, et al. Modulation of K-Ras–dependent lung tumorigenesis by microRNA-21. Cancer Cell. 2010;18(3):282–293.
70. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Research. 2005;65(14):6029–6033.
71. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. Journal of Biological Chemistry. 2008;283(2):1026–1033.
72. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Research. 2008;18(3):350–359.
73. Selcuklu SD, Donoghue MTA, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochemical Society Transactions. 2009;37(4):918–925.
74. Wang Z, Li Y, Kong D, Sarkar FH. The role of microRNAs in epithelial-mesenchymal transition induced by transforming growth factor-β in cancer. Journal of Cellular and Molecular Medicine. 2010;14(10):2343–2354.
75. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology. 2008;10(5):593–601.
76. Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. Journal of Biological Chemistry. 2008;283(22):14910–14914.
77. Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Research. 2008;68(19):7846–7854.
78. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes & Development. 2008;22(7):894–907.
79. Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Reports. 2008;9(6):582–589.
80. Gibbons DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, et al. Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes & Development. 2009;23(18):2140–2151.
81. Brabletz S, Brabletz T. The ZEB/miR-200 feedback loop – a motor of cellular plasticity in development and cancer? EMBO Reports. 2010;11(9):670–677.
82. Schliekelman MJ, Gibbons DL, Faca VM, Creighton CJ, Rizvi ZH, Zhang Q, et al. Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer. Cancer Research. 2011;71(24):7670–7682.
83. Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK. MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Molecular Cancer Therapeutics. 2009;8(5):1055–1066.
84. Howe EN, Cochrane DR, Richer JK. The miR-200 and miR-221/222 microRNA families: opposing effects on epithelial identity. Journal of Mammary Gland Biology and Neoplasia. 2012;17(1):65–77.
85. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449(7163):682–688.
86. Gee HE, Camps C, Buffa FM, Colella S, Sheldon H, Gleadle JM, et al. MicroRNA-10b and breast cancer metastasis. Nature. 2008;455(7216):919–922.
87. Hurst DR, Edmonds MD, Welch DR. Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Research. 2009;69(19):7495–7498.
88. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nature Cell Biology. 2008;10(2):202–210.
89. Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451(7175):147–152.
90. Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC, et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009;137(6):1032–1046.
91. Zhang J, Yang J, Zhan Y, Shi H, Huang J, Jin M, et al. MicroRNA-196a promotes an aggressive phenotype in colorectal cancer via regulation of HOXB7. Molecular Cancer. 2014;13:48.
92. Hou J, Lin L, Zhou W, Wang Z, Ding G, Dong Q, et al. Identification of miR-151 as a metastasis-promoting microRNA in hepatocellular carcinoma. Cancer Research. 2011;71(7):2450–2459.
93. Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proceedings of the National Academy of Sciences. 2008;105(36):13556–13561.
94. Khew-Goodall Y, Goodall GJ. Myc-modulated miR-9 makes E-cadherin a target for metastasis. Nature Cell Biology. 2010;12(10):101–112.
95. Sun Y, Fang R, Li C, Li L, Li F, Ye X, et al. Hsa-miR-155 promotes gastric cancer growth and invasion by regulating SOCS1. Cancer Research. 2014;74(17):4905–4915.
96. Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, et al. MicroRNA-155 functions as an oncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Research. 2010;70(8):3119–3127.
97. Wang B, Li J, Sun M, Sun L, Zhang X. miR-155 promotes gastric cancer cell proliferation by targeting FOXO3a. Oncology Reports. 2016;36(4):2115–2123.
98. O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nature Reviews Immunology. 2010;10(2):111–122.
99. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-α stimulation and their possible roles in regulating the response to endotoxin shock. Journal of Immunology. 2007;179(8):5082–5089.
100. Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N, et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice. Proceedings of the National Academy of Sciences. 2006;103(18):7024–7029.REFERENCES
101. Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA. 2005;102(10):3627–3632.
102. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA. 2007;104(40):15805–15810.
103. Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CEA, Callegari E, et al. MicroRNA-29b induces global DNA hypomethylation in acute myeloid leukemia by targeting DNA methyltransferases. Proc Natl Acad Sci USA. 2009;106(34):13544–13549.
104. Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, et al. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008;68(11):4123–4132.
105. Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Körner H, et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle. 2008;7(16):2591–2600.
106. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447(7148):1130–1134.
107. Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26(5):745–752.
108. Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007;26(5):731–743.
109. Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007;17(15):1298–1307.
110. Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010;17(2):193–199.
111. Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY. MicroRNA-34b and microRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 2007;67(18):8433–8438.
112. Wang LG, Gu J. p53-dependent transcriptional regulation of miR-34 family. Cell Cycle. 2011;10(12):1847–1848.
113. Siemens H, Jackstadt R, Hünten S, Kaller M, Menssen A, Götz U, et al. miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle. 2011;10(24):4256–4271.
114. Kim NH, Kim HS, Li XY, Lee I, Choi HS, Kang SE, et al. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial–mesenchymal transition. J Cell Biol. 2011;195(3):417–433.
115. Li N, Fu H, Tie Y, Hu Z, Kong W, Wu Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275(1):44–53.
116. Migliore C, Petrelli A, Ghiso E, Corso S, Capparuccia L, Eramo A, et al. MicroRNAs impair MET-mediated invasive growth. Cancer Res. 2008;68(24):10128–10136.
117. Siemens H, Jackstadt R, Hünten S, Kaller M, Menssen A, Götz U, et al. miR-34 regulates Wnt signaling and suppresses colorectal cancer metastasis. Cancer Res. 2011;71(24):1–10.
118. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids—the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011;8(8):467–477.
119. Etheridge A, Lee I, Hood L, Galas D, Wang K. Extracellular microRNA: a new source of biomarkers. Mutat Res. 2011;717(1–2):85–90.
120. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–659.
121. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470–1476.
122. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13–21.
123. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101(10):2087–2092.
124. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105(30):10513–10518.
125. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006.
126. Schwarzenbach H, Nishida N, Calin GA, Pantel K. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014;11(3):145–156.
127. Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011;39(16):7223–7233.
128. Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA. 2011;108(12):5003–5008.
129. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011;13(4):423–433.
130. Chen X, Liang H, Zhang J, Zen K, Zhang CY. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol. 2012;22(3):125–132.
131. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Competitive interactions of cancer cells and normal cells via secretory microRNAs. J Biol Chem. 2012;287(2):1397–1405.
132. Mittelbrunn M, Gutiérrez-Vázquez C, Villarroya-Beltri C, González S, Sánchez-Cabo F, González MÁ, et al. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun. 2011;2:282.
133. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MAJ, Hopmans ES, Lindenberg JL, et al. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA. 2010;107(14):6328–6333.
134. Squadrito ML, Baer C, Burdet F, Maderna C, Gilfillan GD, Lyle R, et al. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep. 2014;8(5):1432–1446.
135. Villarroya-Beltri C, Baixauli F, Gutiérrez-Vázquez C, Sánchez-Madrid F, Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin Cancer Biol. 2014;28:3–13.
136. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–289.
137. Yáñez-Mó M, Siljander PRM, Andreu Z, Zavec AB, Borràs FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.
138. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2(8):569–579.
139. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478).
140. O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol. 2020;21(10):585–606.
141. Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226–1232.
142. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–383.
143. Mathieu M, Martin-Jaular L, Lavieu G, Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9–17.
144. Alix-Panabières C, Pantel K. Liquid biopsy: from discovery to clinical application. Cancer Discov. 2021;11(4):858–873.
145. Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20(2):71–88.
146. Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223–238.
147. Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol. 2017;14(9):531–548.
148. Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic—implementation issues and future challenges. Nat Rev Clin Oncol. 2021;18(5):297–312.
149. Merker JD, Oxnard GR, Compton C, Diehn M, Hurley P, Lazar AJ, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;36(16):1631–1641.
150. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10(8):472–484.
151. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.
152. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–990.
153. Dawson SJ, Tsui DWY, Murtaza M, Biggs H, Rueda OM, Chin SF, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–1209.
154. Murtaza M, Dawson SJ, Tsui DWY, Gale D, Forshew T, Piskorz AM, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013;497(7447):108–112.
155. Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017;545(7655):446–451.
156. Wan JCM, Heider K, Gale D, Murphy S, Fisher E, Mouliere F, et al. ctDNA monitoring using patient-specific sequencing and integration of variant reads. Sci Transl Med. 2020;12(548).
157. Cristiano S, Leal A, Phallen J, Fiksel J, Adleff V, Bruhm DC, et al. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature. 2019;570(7761):385–389.
158. Mouliere F, Chandrananda D, Piskorz AM, Moore EK, Morris J, Ahlborn LB, et al. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci Transl Med. 2018;10(466).
159. Abbosh C, Swanton C, Birkbak NJ. Clonal haematopoiesis: a source of biological noise in cell-free DNA analyses. Ann Oncol. 2019;30(3):358–359.
160. Razavi P, Li BT, Brown DN, Jung B, Hubbell E, Shen R, et al. High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat Med. 2019;25(12):1928–1937.
161. Merker JD, Oxnard GR, Compton C, Diehn M, Hurley P, Lazar AJ, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;36(16):1631–1641.
162. S. Shamsizadeh, S. Goliaei, CAMIRADA: Cancer microRNA Association Discovery Algorithm, a Case Study on Breast Cancer,
Journal of Biomedical Informatics 94 (2019) 103180.
163. A.R. Halvorsen, Å. Helland, P. Gromov, V.T. Wielenga, M.-L.M. Talman, N. Brünner, V. Sandhu, A.L. Børresen‐Dale, I. Gromova,
V.D. Haakensen, Profiling of Micro
Biomarkers for Prognostic Classification and Detection of Cancer, Molecular Oncology 11(2) (2016) 220-234.
Article Sidebar
Published
Jan 9, 2026
Article Details
How to Cite
1.
MicroRNA Regulation in Cancer: Insights into Diagnosis, Prognosis, and Treatment. Pharm Pract (Granada) [Internet]. 2026 Jan. 9 [cited 2026 Jan. 25];23(4):1-17. Available from: https://www.pharmacypractice.org/index.php/pp/article/view/3205
Section
Review
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
1.
MicroRNA Regulation in Cancer: Insights into Diagnosis, Prognosis, and Treatment. Pharm Pract (Granada) [Internet]. 2026 Jan. 9 [cited 2026 Jan. 25];23(4):1-17. Available from: https://www.pharmacypractice.org/index.php/pp/article/view/3205