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ISSN 打印: 1045-4403
ISSN 在线: 2162-6502


DOI: 10.1615/CritRevEukaryotGeneExpr.2019030056
pages 521-528

Molecular Mechanisms and Therapeutic Potential of miR-493 in Cancer

Lingli Huang
Department of Pharmacy, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China
Lingwei Huang
Department of Applied Physics, University of Eastern Finland, 70211 Kuopio, Finland
Ziwei Li
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
Qing Wei
Department of Pharmacy, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China


MicroRNAs (miRNAs) are highly conserved short noncoding RNAs with the capacity of regulating gene expression posttranscriptionally. In this process, miRNAs partially bind complementary sites of target mRNAs. Among miRNAs, miR-493 performs important functions under diverse physiological conditions and participates in different pathogeneses, including pancreatic cancer, gastric cancer, and breast cancer. Differential expression of miR-493 plays a vital role in the generation, metastasis, and recurrence of tumors. Above all, increasing evidence indicates that miR-493 inhibits the generation and development of tumors by activating the Wnt/Β-catenin, Wnt/PCP, MEK/ERK, or PI3K/AKT signaling pathway, suggesting possibilities for miR-493 as an effective adjuvant cancer therapy. In this review, we discuss and summarize the biological mechanisms of miR-493 and its potential in cancer therapy. This review may provide a better understanding of the biological functions of miR-493 in tumors and provide important clues to cancer treatment.


  1. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-97.

  2. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15-20.

  3. Liu X, Chen Z, Yu J, Xia J, Zhou X. MicroRNA profiling and head and neck cancer. Comp Funct Genom. 2009:837514.

  4. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. 2002;298(5595):1039-43.

  5. Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704-14.

  6. Bar M, Wyman SK, Fritz BR, Qi JL, Garg KS, Parkin RK, Kroh EM, Bendoraite A, Mitchell PS, Nelson AM, Ruzzo WL, Ware C, Radich JP, Gentleman R, Ruohola-Baker H, Tewari M. MicroRNA discovery and profiling in human embryonic stem cells by deep sequencing of small RNA libraries. Stem Cells. 2008;26(10):2496-505.

  7. Zhi D, Zhao X, Dong M,Yan CC. miR-493 inhibits pro-liferation and invasion in pancreatic cancer cells and inversely regulated hERG1 expression. Oncol Lett. 2017;14(6):7398-404.

  8. Zhou W, Zhang C, Jiang H, Zhang Z, Xie L, He X. MiR-493 suppresses the proliferation and invasion of gastric cancer cells by targeting RhoC. Iran J Basic Med Sci. 2015;18(10):1027-33.

  9. Kumar AS, Jagadeeshan S, Pitani RS, Ramshankar V, Venkitasamy K, Venkatraman G, Rayala SK. Snail-modulated microRNA 493 forms a negative feedback loop with the insulin-like growth factor 1 receptor pathway and blocks tumorigenesis. Mol Cell Biol. 2017;37(6):e00510-16.

  10. Duregon E, Rapa I, Votta A, Giorcelli J, Daffara F, Terzolo M, Scagliotti GV, Volante M, Papotti M. MicroRNA expression patterns in adrenocortical carcinoma variants and clinical pathologic correlations. Hum Pathol. 2014;45(8):1555-62.

  11. Zhao L, Feng X, Song X, Zhou H, Zhao Y, Cheng L, Jia L. miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4. Oncol Rep. 2016;36(2):1007-15.

  12. Deng J, Ma M, Jiang W, Zhang HF, Cui SP. miR-493 contributes to the proliferation and cell cycle in prostate cancer cells by repressing PHLPP2. Int J Clin Exper Med. 2016;9(8):15728-36.

  13. Ueno K, Hirata H, Majid S, Yamamura S, Shahryari V, Tabatabai ZL, Hinoda Y, Dahiya R. Tumor suppressor microRNA-493 decreases cell motility and migration ability in human bladder cancer cells by downregulating RhoC and FZD4. Mol Cancer Ther. 2012;11(1):244-53.

  14. Lee H, Park CS, Deftereos G, Morihara J, Stern JE, Hawes SE, Swisher E, Kiviat NB, Feng Q. MicroRNA expression in ovarian carcinoma and its correlation with clinicopath-ological features. World J Surg Oncol. 2012;10:174.

  15. Zhao J, Xu T, Wang F, Cai W, Chen L. miR-493-5p suppresses hepatocellular carcinoma cell proliferation through targeting GP73. Biomed Pharmacother. 2017;90:744-51.

  16. Gu Y, Cheng Y, Song Y, Zhang Z, Deng M, Wang C, Zheng G, He Z. MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1. PLoS One. 2014;9(8):e102602.

  17. Cui A, Jin Z, Gao Z, Jin M, Zhu L, Li L, Jin C, An Y. Downregulation of miR-493 promoted melanoma proliferation by suppressing IRS4 expression. Tumour Biol. 2017;39(5):1.

  18. Stilling G, Sun ZF, Zhang SY, Jin L, Righi A, Gabor K, Korbonits M, Scheithauer BW, Kovacs K, Lloyd RV. MicroRNA expression in ACTH-producing pituitary tumors: up-regulation of microRNA-122 and -493 in pituitary carcinomas. Endocrine. 2010;38(1):67-75.

  19. Qian M, Gong H, Yang X, Zhao J, Yan W, Lou Y, Peng D, Li Z, Xiao J. MicroRNA-493 inhibits the proliferation and invasion of osteosarcoma cells through directly targeting specificity protein 1. Oncol Lett. 2018;15(5):8149-56.

  20. Kleemann M, Schneider H, Unger K, Bereuther J, Fischer S, Sander P, Marion Schneider E, Fischer-Posovszky P, Riedel CU, Handrick R, Otte K. Induction of apoptosis in ovarian cancer cells by miR-493-3p directly targeting AKT2, STK38L, HMGA2, ETS1, and E2F5. Cell Mol Life Sci. 2019;76(3):539-59.

  21. Xu Y, Ge K, Lu J, Huang J, Wei W, Huang Q. MicroRNA-493 suppresses hepatocellular carcinoma tumori-genesis through down-regulation of anthrax toxin receptor 1 (ANTXR1) and R-Spondin 2 (RSPO2). Biomed Pharmacother. 2017;93:334-43.

  22. Wang S, Wang X, Li JF, Meng S, Liang Z, Xu X, Zhu Y, Li SQ, Wu J, Xu MJ, Ji AL, Lin YW, Liu B, Zheng XY, Xie B, Xie LP. c-Met, CREB1 and EGFR are involved in miR-493-5p inhibition of EMT via AKT/GSK-3 beta/Snail signaling in prostate cancer. Oncotarget. 2017;8(47):82303-13.

  23. Domanitskaya N, Wangari-Talbot J, Jacobs J, Peiffer E, Mahdaviyeh Y, Paulose C, Malofeeva E, Foster K, Cai KQ, Zhou Y, Egleston B, Hopper-Borge E. Abcc10 status affects mammary tumour growth, metastasis, and docetaxel treatment response. Brit J Cancer. 2014;111(4):696-707.

  24. Qin C, Huang RY, Wang ZX. Potential role of miR-100 in cancer diagnosis, prognosis, and therapy. Tumour Biol. 2015;36(3):1403-9.

  25. Subramani R, Lopez-Valdez R, Arumugam A, Nandy S, Boopalan T, Lakshmanaswamy R. Targeting insulin-like growth factor 1 receptor inhibits pancreatic cancer growth and metastasis. PLoS One. 2014;9(5):e97016.

  26. Clevers H, Nusse R. Wnt/p-catenin signaling and disease. Cell. 2012;149(6):1192-205.

  27. Polakis P. Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 2012;4(5):a008052.

  28. Behari J. The Wnt/beta-catenin signaling pathway in liver biology and disease. Exp Rev Gastroenterol Hepatol. 2010;4(6):745-56.

  29. Wei W, Ge KK, Xu YQ, Huang JJ, Huang QS. MicroRNA-493 inhibited proliferation, migration and tumor formation of breast cancer cell MCF7. Chinese J Cell Biol. 2015;37(4):486-92.

  30. Abrami L, Kunz B, Deuquet J, Bafico A, Davidson G, van der Goot FG. Functional interactions between anthrax toxin receptors and the WNT signalling protein LRP6. Cell Microbiol. 2008;10(12):2509-19.

  31. Kim KA, Wagle M, Tran K, Zhan X, Dixon MA, Liu S, Gros D, Korver W, Yonkovich S, Tomasevic N, Binnerts M, Abo A. R-spondin family members regulate the Wnt pathway by a common mechanism. Mol Biol Cell. 2008;19(6):2588-96.

  32. Zhang H, Han X, Wei B, Fang J, Hou X, Lan T, Wei H. RSPO2 enhances cell invasion and migration via the WNT/beta-catenin pathway in human gastric cancer. J Cell Biochem. 2019;120(4):5813-24.

  33. Gerlach JP, Emmink BL, Nojima H, Kranenburg O, Maurice MM. Wnt signalling induces accumulation of phosphorylated beta-catenin in two distinct cytosolic complexes. Open Biol. 2014;4(11):140120.

  34. Sakai H, Sato A, Aihara Y, Ikarashi Y, Midorikawa Y, Kracht M, Nakagama H, Okamoto K. MKK7 mediates miR-493-dependent suppression of liver metastasis of colon cancer cells. Cancer Sci. 2014;105(4):425-30.

  35. Ciruna B, Jenny A, Lee D, Mlodzik M, Schier AF. Planar cell polarity signalling couples cell division and morphogenesis during neurulation. Nature. 2006;439(7073):220-4.

  36. Tao Q, Yokota C, Puck H, Kofron M, Birsoy B, Yan D, Asashima M, Wylie CC, Lin X, Heasman J. Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos. Cell. 2005;120(6):857-71.

  37. Alla V, Engelmann D, Niemetz A, Pahnke J, Schmidt A, Kunz M, Emmrich S, Steder M, Koczan D, Putzer BM. E2F1 in melanoma progression and metastasis. J Natl Cancer Inst. 2010;102(2):127-33.

  38. Calvo F, Agudo-Ibanez L, Crespo P. The Ras-ERK pathway: understanding site-specific signaling provides hope of new anti-tumor therapies. Bioessays. 2010;32(5):412-21.

  39. Xu X, Zhu Y, Liang Z, Li S, Xu X, Wang X, Wu J, Hu Z, Meng S, Liu B, Qin J, Xie L, Zheng X. c-Met and CREB1 are involved in miR-433-mediated inhibition of the epithelial-mesenchymal transition in bladder cancer by regulating Akt/GSK-3beta/Snail signaling. Cell Death Dis. 2016;7:e2088.

  40. Lee MW, Kim DS, Lee JH, Lee BS, Lee SH, Jung HL, Sung KW, Kim HT, Yoo KH, Koo HH. Roles of AKT1 and AKT2 in non-small cell lung cancer cell survival, growth, and migration. Cancer Sci. 2011;102(10):1822-8.

  41. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516.

  42. Becchetti A, Crescioli S, Zanieri F, Petroni G, Mercatelli R, Coppola S, Gasparoli L, D'Amico M, Pillozzi S, Crociani O, Stefanini M, Fiore A, Carraresi L, Morello V, Manoli S, Brizzi MF, Ricci D, Rinaldi M, Masi A, Schmidt T, Quercioli F, Defilippi P, Arcangeli A. The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression. Sci Signal. 2017;10(473):aaf3236.

  43. Arcangeli A, Becchetti A. hERG channels: from antitar-gets to novel targets for cancer therapy. Clin Cancer Res. 2017;23(1):3-5.

  44. Cao P. Upregulation of miR-493 inhibits proliferation and migration of osteosarcoma cells by targeting E2F1. J Practical Med. 2018;34(6):920-3.

  45. Lin H, Hao Y, Zhao Z, Tong Y. Sirtuin 6 contributes to migration and invasion of osteosarcoma cells via the ERK1/2/ MMP9 pathway. FEBS Open Bio. 2017;7(9):1291-301.

  46. Cheng Y. miR-493 decreases cell proliferation ability and migration ability in lung cancer cells by down-regulating E2F1 and RhoC [dissertation]. Central South University; 2013. p. 18-29; Chapter 3.

  47. Jia X, Li N, Peng C, Deng Y, Wang J, Deng M, Lu M, Yin J, Zheng G, Liu H, He Z. miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells. Oncotarget. 2016; 7(6):7044-54.

  48. Yu Q, Li P, Weng ML, Wu S, Zhang YF, Chen X, Zhang Q, Shen GX, Ding XT, Fu S. Nano-vesicles are a potential tool to monitor therapeutic efficacy of carbon ion radiotherapy in prostate cancer. J Biomed Nanotechnol. 2018;14(1):168-78.

  49. Li JF, Meng S, Xu MJ, Wang S, He LJ, Xu X, Wang X, Xie LP. Downregulation of N-6-methyladenosine binding YTHDF2 protein mediated by miR-493-3p suppresses prostate cancer by elevating N-6-methyladenosine levels. Oncotarget. 2018;9(3):3752-64.

  50. Okamoto K, Ishiguro T, Midorikawa Y, Ohata H, Izumiya M, Tsuchiya N, Sato A, Sakai H, Nakagama H. miR-493 induction during carcinogenesis blocks meta-static settlement of colon cancer cells in liver. EMBO J. 2012;31(7):1752-63.

  51. Wang G, Fang X, Han M, Wang X, Huang Q. MicroR- NA-493-5p promotes apoptosis and suppresses proliferation and invasion in liver cancer cells by targeting VAMP2. Int J Mol Med. 2018;41(3):1740-8.

  52. Gailhouste L. Rescue of the epigenetically silenced microRNA miR-493-5p inhibits liver cancer progression. Hepatology. 2017;66:375a.

  53. Liang Z, Kong R, He Z, Lin LY, Qin SS, Chen CY, Xie ZQ, Yu F, Sun GQ, Li CG, Fu D, Jiang GX, Chen J, Ma YS. High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1. Oncotarget. 2017;8(29):47389-99.

  54. Wang W, Zhao LJ, Tan YX, Ren H, Qi ZT. MiR-138 induces cell cycle arrest by targeting cyclin D3 in hepatocellular carcinoma. Carcinogenesis. 2012;33(5):1113-20.

  55. Chen Z, Zeng H, Guo Y, Liu P, Pan H, Deng A, Hu J. miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc. J Exp Clin Cancer Res. 2010;29:151.