miR-145 inhibits proliferation and migration of breast cancer cells by directly or indirectly regulating TGF-β1 expression

Ding,Yanling; Zhang,Chunfu; Zhang,Jiahui; Zhang,Nannan; Li,Tao; Fang,Jie; Zhang,Yi; Zuo,Feiyang; Tao,Zehua; Tang,Shengnan; Zhu,Wei; Chen,Huabiao; Sun,Xiaochun

doi:10.3892/ijo.2017.3945

miR-145 inhibits proliferation and migration of breast cancer cells by directly or indirectly regulating TGF-β1 expression

Authors:
- Yanling Ding
- Chunfu Zhang
- Jiahui Zhang
- Nannan Zhang
- Tao Li
- Jie Fang
- Yi Zhang
- Feiyang Zuo
- Zehua Tao
- Shengnan Tang
- Wei Zhu
- Huabiao Chen
- Xiaochun Sun
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Affiliations: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, The Second People's Hospital of Kunshan, Kunshan, Jiangsu 215300, P.R. China, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
Published online on: April 4, 2017 https://doi.org/10.3892/ijo.2017.3945
Pages: 1701-1710

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Abstract

Studies have demonstrated low expression of miR-145 associated with cell proliferation and migration in a wide variety of tumors. Here, we studied the expression of miR-145 in relation to the occurrence and development of breast cancer. Total RNA from breast cancer tissue and corresponding adjacent normal tissue was extracted and used to detect miR-145 expression by quantitative real-time polymerase chain reaction (qRT-PCR). We also transfected breast cancer cells with hsa-miR-145 mimics, hsa-miR-145 inhibitor, mimics negative control (mimics NC) or inhibitor negative control (inhibitor NC). Cell proliferation was analyzed by colony formation assays and methyl thiazolyl tetrazolium assays. Cell proliferation in breast cancer cells was decreased after overexpression of miR-145 and increased following miR-145 suppression. Cell migration and invasion were assessed using Transwell and wound healing assays, respectively, and were also decreased after overexpression of miR-145 and increased after miR-145 suppression in breast cancer cells. Finally, western blot assays showed that overexpression of miR-145 inhibited expression of transforming growth factor-β1 (TGF-β1). Collectively, these data suggest that miR-145 may inhibit TGF-β1 protein expression which may in turn contribute to tumor formation.

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1	Gündüz UR, Gunaldi M, Isiksacan N, Gündüz S, Okuturlar Y and Kocoglu H: A new marker for breast cancer diagnosis, human epididymis protein 4: A preliminary study. Mol Clin Oncol. 5:355–360. 2016.PubMed/NCBI
2	Lu J, Steeg PS, Price JE, Krishnamurthy S, Mani SA, Reuben J, Cristofanilli M, Dontu G, Bidaut L, Valero V, et al: Breast cancer metastasis: Challenges and opportunities. Cancer Res. 69:4951–4953. 2009. View Article : Google Scholar : PubMed/NCBI
3	Zhang C, Liu K, Li T, Fang J, Ding Y, Sun L, Tu T, Jiang X, Du S, Hu J, et al: miR-21: A gene of dual regulation in breast cancer. Int J Oncol. 48:161–172. 2016.
4	Nogales-Cadenas R, Cai Y, Lin JR, Zhang Q, Zhang W, Montagna C and Zhang ZD: MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice. Breast Cancer Res. 18:752016. View Article : Google Scholar : PubMed/NCBI
5	Carthew RW and Sontheimer EJ: Origins and mechanisms of miRNAs and siRNAs. Cell. 136:642–655. 2009. View Article : Google Scholar : PubMed/NCBI
6	Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
7	Kloosterman WP and Plasterk RH: The diverse functions of microRNAs in animal development and disease. Dev Cell. 11:441–450. 2006. View Article : Google Scholar : PubMed/NCBI
8	Kou B, Gao Y, Du C, Shi Q, Xu S, Wang CQ, Wang X, He D and Guo P: miR-145 inhibits invasion of bladder cancer cells by targeting PAK1. Urol Oncol. 32:846–854. 2014. View Article : Google Scholar : PubMed/NCBI
9	Qin J, Wang F, Jiang H, Xu J, Jiang Y and Wang Z: MicroRNA-145 suppresses cell migration and invasion by targeting paxillin in human colorectal cancer cells. Int J Clin Exp Pathol. 8:1328–1340. 2015.PubMed/NCBI
10	Zhang Y and Lin Q: MicroRNA-145 inhibits migration and invasion by down-regulating FSCN1 in lung cancer. Int J Clin Exp Med. 8:8794–8802. 2015.PubMed/NCBI
11	Park SJ, Kim JG, Kim ND, Yang K, Shim JW and Heo K: Estradiol, TGF-β1 and hypoxia promote breast cancer stemness and EMT-mediated breast cancer migration. Oncol Lett. 11:1895–1902. 2016.PubMed/NCBI
12	Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ, Decker T, Eusebi V, Fox SB, Ichihara S, Jacquemier J, Lakhani SR, et al: Breast cancer prognostic classification in the molecular era: The role of histological grade. Breast Cancer Res. 12:2072010. View Article : Google Scholar : PubMed/NCBI
13	Liu K, Zhang C, Li T, Ding Y, Tu T, Zhou F, Qi W, Chen H and Sun X: Let-7a inhibits growth and migration of breast cancer cells by targeting HMGA1. Int J Oncol. 46:2526–2534. 2015.PubMed/NCBI
14	Lin S and Gregory RI: MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 15:321–333. 2015. View Article : Google Scholar : PubMed/NCBI
15	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 94:776–780. 2006. View Article : Google Scholar : PubMed/NCBI
16	Hiyoshi Y, Kamohara H, Karashima R, Sato N, Imamura Y, Nagai Y, Yoshida N, Toyama E, Hayashi N, Watanabe M, et al: MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. Clin Cancer Res. 15:1915–1922. 2009. View Article : Google Scholar : PubMed/NCBI
17	Ma L, Teruya-Feldstein J and Weinberg RA: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 449:682–688. 2007. View Article : Google Scholar : PubMed/NCBI
18	Vaknin-Dembinsky A, Charbit H, Brill L, Abramsky O, Gur-Wahnon D, Ben-Dov IZ and Lavon I: Circulating microRNAs as biomarkers for rituximab therapy, in neuromyelitis optica (NMO). J Neuroinflammation. 13:1792016. View Article : Google Scholar : PubMed/NCBI
19	Li Y, Deng X, Zeng X and Peng X: The role of miR-148a in cancer. J Cancer. 7:1233–1241. 2016. View Article : Google Scholar : PubMed/NCBI
20	Li LZ, Zhang CZ, Liu LL, Yi C, Lu SX, Zhou X, Zhang ZJ, Peng YH, Yang YZ and Yun JP: miR-720 inhibits tumor invasion and migration in breast cancer by targeting TWIST1. Carcinogenesis. 35:469–478. 2014. View Article : Google Scholar
21	Ni F, Gui Z, Guo Q, Hu Z, Wang X, Chen D and Wang S: Downregulation of miR-362-5p inhibits proliferation, migration and invasion of human breast cancer MCF7 cells. Oncol Lett. 11:1155–1160. 2016.PubMed/NCBI
22	Cisneros-Soberanis F, Andonegui MA and Herrera LA: miR-125b-1 is repressed by histone modifications in breast cancer cell lines. Springerplus. 5:9592016. View Article : Google Scholar : PubMed/NCBI
23	Zhao L, Feng X, Song X, Zhou H, Zhao Y, Cheng L and Jia L: miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4. Oncol Rep. 36:1007–1015. 2016.PubMed/NCBI
24	Li C, Xu N, Li YQ, Wang Y and Zhu ZT: Inhibition of SW620 human colon cancer cells by upregulating miRNA-145. World J Gastroenterol. 22:2771–2778. 2016. View Article : Google Scholar : PubMed/NCBI
25	Sun Z, Zhang A, Jiang T, Du Z, Che C and Wang F: MiR-145 suppressed human retinoblastoma cell proliferation and invasion by targeting ADAM19. Int J Clin Exp Pathol. 8:14521–14527. 2015.
26	Jiang SB, He XJ, Xia YJ, Hu WJ, Luo JG, Zhang J and Tao HQ: MicroRNA-145-5p inhibits gastric cancer invasiveness through targeting N-cadherin and ZEB2 to suppress epithelial-mesenchymal transition. Onco Targets Ther. 9:2305–2315. 2016.PubMed/NCBI
27	Li Y, Li Y, Liu J, Fan Y, Li X, Dong M, Liu H and Chen J: Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer. Cancer Biol Ther. 17:272–279. 2016. View Article : Google Scholar : PubMed/NCBI
28	Dong R, Liu X, Zhang Q, Jiang Z, Li Y, Wei Y, Li Y, Yang Q, Liu J, Wei JJ, et al: miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma. Oncotarget. 5:10816–10829. 2014. View Article : Google Scholar : PubMed/NCBI
29	Chen X, Dong C, Law PT, Chan MT, Su Z, Wang S, Wu WK and Xu H: MicroRNA-145 targets TRIM2 and exerts tumor-suppressing functions in epithelial ovarian cancer. Gynecol Oncol. 139:513–519. 2015. View Article : Google Scholar : PubMed/NCBI
30	Ding MJ, Su KE, Cui GZ, Yang WH, Chen L, Yang M, Liu YQ and Dai DL: Association between transforming growth factor-β1 expression and the clinical features of triple negative breast cancer. Oncol Lett. 11:4040–4044. 2016.PubMed/NCBI
31	Zheng W: Genetic polymorphisms in the transforming growth factor-beta signaling pathways and breast cancer risk and survival. Methods Mol Biol. 472:265–277. 2009. View Article : Google Scholar
32	Eder IE, Stenzl A, Hobisch A, Cronauer MV, Bartsch G and Klocker H: Transforming growth factors-beta 1 and beta 2 in serum and urine from patients with bladder carcinoma. J Urol. 156:953–957. 1996. View Article : Google Scholar : PubMed/NCBI
33	Tsushima H, Kawata S, Tamura S, Ito N, Shirai Y, Kiso S, Imai Y, Shimomukai H, Nomura Y, Matsuda Y, et al: High levels of transforming growth factor beta 1 in patients with colorectal cancer: Association with disease progression. Gastroenterology. 110:375–382. 1996. View Article : Google Scholar : PubMed/NCBI
34	Comerci JT Jr, Runowicz CD, Flanders KC, De Victoria C, Fields AL, Kadish AS and Goldberg GL: Altered expression of transforming growth factor-beta 1 in cervical neoplasia as an early biomarker in carcinogenesis of the uterine cervix. Cancer. 77:1107–1114. 1996. View Article : Google Scholar : PubMed/NCBI
35	Friess H, Yamanaka Y, Büchler M, Ebert M, Beger HG, Gold LI and Korc M: Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology. 105:1846–1856. 1993. View Article : Google Scholar : PubMed/NCBI
36	Sheen-Chen SM, Chen HS, Sheen CW, Eng HL and Chen WJ: Serum levels of transforming growth factor beta1 in patients with breast cancer. Arch Surg. 136:937–940. 2001. View Article : Google Scholar : PubMed/NCBI
37	Chen JY, Liu JH, Wu HD, Lin KH, Chang KC and Liou YM: Transforming growth factor-β1 T869C gene polymorphism is associated with acquired sick sinus syndrome via linking a higher serum protein level. PLoS One. 11:e01586762016. View Article : Google Scholar
38	Kelly RJ and Morris JC: Transforming growth factor-beta: A target for cancer therapy. J Immunotoxicol. 7:15–26. 2010. View Article : Google Scholar
39	Hornstein E, Mansfield JH, Yekta S, Hu JK, Harfe BD, McManus MT, Baskerville S, Bartel DP and Tabin CJ: The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 438:671–674. 2005. View Article : Google Scholar : PubMed/NCBI