MicroRNA-495 induces breast cancer cell migration by targeting JAM-A

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression. The deregulated expression of miRNAs is associated with a variety of diseases, including breast cancer. In the present study, we found that miR-495 was markedly up-regulated in clinical breast cancer samples by quantitative real time-PCR (qRT-PCR). Junctional adhesion molecule A (JAM-A) was predicted to be a potential target of miR-495 by bioinformatics analysis and was subsequently verified by luciferase assay and Western blotting. JAM-A was found to be negatively correlated with the migration of breast cancer cells through loss-of-function and gain-offunction assays, and the inhibition of JAM-A by miR-495 promoted the migration of MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of JAM-A could restore miR-495-induced breast cancer cell migration. Taken together, our findings suggest that miR-495 could facilitate breast cancer progression through the repression of JAM-A, making this miRNA a potential therapeutic target.

Keywords

miR-495 / JAM-A / breast cancer / migration

References

[1] Ambros V (2001) microRNAs: tiny regulators with great potential. Cell107: 823-826

[2] Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell116: 281-297

[3] Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell136: 215-233

[4] Bendre M, Gaddy D, Nicholas RW, Suva LJ (2003). Breast cancer metastasis to bone: it is not all about PTHrP. Clin Orthop Relat ResS39-S45

[5] Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved incancers. Proc Natl Acad Sci USA101: 2999-3004

[6] Cao M, Hou D, Liang H, Gong F, Wang Y, Yan X, Jiang X, Wang C, Zhang J, Zen K (2014) miR-150 promotes the proliferation and migration of lung cancer cells by targeting SRC kinase signalling inhibitor 1. Eur J Cancer50: 1013-1024

[7] Chen SM, Chen HC, Chen SJ, Huang CY, Chen PY, Wu TW, Feng LY, Tsai HC, Lui TN, Hsueh C (2013) MicroRNA-495 inhibits proliferation of glioblastoma multiforme cells by downregulating cyclin-dependent kinase 6. World J Surg Oncol11: 87

[8] Chu H, Chen X, Wang H, Du Y, Wang Y, Zang W, Li P, Li J, Chang J, Zhao G (2014) MiR-495 regulates proliferation and migration in NSCLC by targeting MTA3. Tumour biol: J Int Soc Oncodev Biol Med35: 3487-3494

[9] Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat rev Genet10: 704-714

[10] DeSantis C, Ma J, Bryan L, Jemal A (2014) Breast cancer statistics, 2013. Cancer J Clin64: 52-62

[11] Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79: 351-379

[12] Feigin ME, Muthuswamy SK (2009) Polarity proteins regulate mammalian cell-cell junctions and cancer pathogenesis. Curr Opin Cell biol 21: 694-700

[13] Fong D, Spizzo G, Mitterer M, Seeber A, Steurer M, Gastl G, Brosch I, Moser P (2012) Low expression of junctional adhesion molecule A is associated with metastasis and poor survival in pancreatic cancer. Ann Surg Oncol19: 4330-4336

[14] Holliday DL, Speirs V (2011) Choosing the right cell line for breast cancer research. Breast Cancer Res13: 215

[15] Hwang-Verslues WW, Chang PH, Wei PC, Yang CY, Huang CK, Kuo WH, Shew JY, Chang KJ, Lee EY, Lee WH (2011) miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1. Oncogene30: 2463-2474

[16] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. Cancer J Clin61: 69-90

[17] Jiang X, Huang H, Li Z, He C, Li Y, Chen P, Gurbuxani S, Arnovitz S, Hong GM, Price C (2012) MiR-495 is a tumor-suppressor microRNA down-regulated in MLL-rearranged leukemia. Proc Natl Acad Sci USA109: 19397-19402

[18] John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS (2004) Human MicroRNA targets. PLoS Biol2: e363

[19] Koshiba H, Hosokawa K, Kubo A, Tokumitsu N, Watanabe A, Honjo H (2009) Junctional adhesion molecule A [corrected] expression in human endometrial carcinoma. Int J Gynecol Cancer19: 208-213

[20] Lee JM, Dedhar S, Kalluri R, Thompson EW (2006) The epithelialmesenchymal transition: new insights in signaling, development, and disease. J Cell Biol172: 973-981

[21] Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of mammalian microRNA targets. Cell115: 787-798

[22] Li Z, Cao Y, Jie Z, Liu Y, Li Y, Li J, Zhu G, Liu Z, Tu Y, Peng G (2012) miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL-3. Cancer Lett323: 41-47

[23] Li Y, Hong F, Yu Z (2013) Decreased expression of microRNA-206 in breast cancer and its association with disease characteristics and patient survival. J Int Med Res41: 596-602

[24] Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA (2005) MicroRNA expression profiles classify human cancers. Nature435: 834-838

[25] Lujambio A, Lowe SW (2012) The microcosmos of cancer. Nature482: 347-355

[26] Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature449: 682-688

[27] Mandell KJ, Parkos CA (2005) The JAM family of proteins. Adv Drug Deliv Rev57: 857-867

[28] McSherry EA, Brennan K, Hudson L, Hill AD, Hopkins AM (2011) Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase. Breast Cancer Res13: R31

[29] Naik MU, Naik TU, Suckow AT, Duncan MK, Naik UP (2008) Attenuation of junctional adhesion molecule-A is a contributing factor for breast cancer cell invasion. Cancer Res68: 2194-2203

[30] Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F (2006) A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell10: 515-527

[31] Olsen PH, Ambros V (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol216: 671-680

[32] Osada H, Takahashi T (2007) MicroRNAs in biological processes and carcinogenesis. Carcinogenesis28: 2-12

[33] Rodriguez LG, Wu X, Guan JL (2005) Wound-healing assay. Methods Mol Biol294: 23-29

[34] Schneeberger EE, Lynch RD (2004) The tight junction: a multifunctional complex. Am J Physiol Cell physiol286: C1213-C1228

[35] Vimalraj S, Miranda PJ, Ramyakrishna B, Selvamurugan N (2013) Regulation of breast cancer and bone metastasis by microRNAs. Dis Markers35: 369-387

[36] Wang Y, Lui WY (2012) Transforming growth factor-beta1 attenuates junctional adhesion molecule-A and contributes to breast cancer cell invasion. Eur J Cancer48: 3475-3487

[37] Yang H, Cho ME, Li TW, Peng H, Ko KS, Mato JM, Lu SC (2013) MicroRNAs regulate methionine adenosyltransferase 1A expression in hepatocellular carcinoma. J Clin Investig123: 285-298

[38] Zhang M, Luo W, Huang B, Liu Z, Sun L, Zhang Q, Qiu X, Xu K, Wang E (2013) Overexpression of JAM-A in non-small cell lung cancer correlates with tumor progression. PloS One8: e79173

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