MicroRNA-106a promotes cell migration and invasion by targeting tissue inhibitor of matrix metalloproteinase 2 in cervical cancer

Li,Xia; Zhou,Qi; Tao,Ling; Yu,Chunxia

doi:10.3892/or.2017.5832

MicroRNA-106a promotes cell migration and invasion by targeting tissue inhibitor of matrix metalloproteinase 2 in cervical cancer

Authors:
- Xia Li
- Qi Zhou
- Ling Tao
- Chunxia Yu
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Affiliations: Department of Obstetrics and Gynecology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China
Published online on: July 18, 2017 https://doi.org/10.3892/or.2017.5832
Pages: 1774-1782

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Abstract

Increasing evidence has demonstrated that miRNAs play a critical role in tumor development and progression. Previous studies have revealed that miR-106a is abnormally expressed in various cancers. However, its function and underlying mechanism in cervical cancer (CC) remains unknown. In this study, we confirmed that the expression of miR-106a was significantly upregulated in both CC cell lines and tissues by qRT-PCR. The increased expression of miR-106a was obviously associated with adverse prognostic features. Moreover, we demonstrated that miR-106a was a novel independent prognostic marker for predicting the 5-year survival of CC patients. The ectopic overexpression of miR‑106a promoted cell migration, invasion and invasion-related gene expression, while downregulated miR-106a reversed the effect. In addition, miR-106a regulated tissue inhibitor of metalloproteinase (TIMP)2 by directly binding to its 3'-UTR, leading to the indution of the expression of matrix metalloproteinases (MMPs). In clinical samples of CC, miR-106a was inversely correlated with TIMP2, which was downregulated in CC. Alteration of TIMP2 expression at least partially abolished the migration, invasion and MMP expression of miR-106a in CC cells. In conclusion, our data indicated that miR-106a promoted the migration, invasion and MMP expression of CC by targeting TIMP2, and may represent a novel potential therapeutic target and prognostic marker for CC.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
3	Dueñas-Gonzalez A, Cetina L, Mariscal I and de la Garza J: Modern management of locally advanced cervical carcinoma. Cancer Treat Rev. 29:389–399. 2003. View Article : Google Scholar : PubMed/NCBI
4	Glick SB, Clarke AR, Blanchard A and Whitaker AK: Cervical cancer screening, diagnosis and treatment interventions for racial and ethnic minorities: A systematic review. J Gen Intern Med. 27:1016–1032. 2012. View Article : Google Scholar : PubMed/NCBI
5	Sakuragi N: Up-to-date management of lymph node metastasis and the role of tailored lymphadenectomy in cervical cancer. Int J Clin Oncol. 12:165–175. 2007. View Article : Google Scholar : PubMed/NCBI
6	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
7	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
8	Su Y, Xiong J, Hu J, Wei X, Zhang X and Rao L: MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis. Oncotarget. 7:68397–68411. 2016. View Article : Google Scholar : PubMed/NCBI
9	Yi Y, Li H, Lv Q, Wu K and Zhang W, Zhang J, Zhu D, Liu Q and Zhang W: miR-202 inhibits the progression of human cervical cancer through inhibition of cyclin D1. Oncotarget. 7:72067–72075. 2016.PubMed/NCBI
10	Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S and Majumder S: MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27^Kip1. J Biol Chem. 283:29897–29903. 2008. View Article : Google Scholar : PubMed/NCBI
11	Tsang WP, Ng EK, Ng SS, Jin H, Yu J, Sung JJ and Kwok TT: Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis. 31:350–358. 2010. View Article : Google Scholar : PubMed/NCBI
12	Jin Y, Peng D, Shen Y, Xu M, Liang Y, Xiao B and Lu J: MicroRNA-376c inhibits cell proliferation and invasion in osteosarcoma by targeting to transforming growth factor-alpha. DNA Cell Biol. 32:302–309. 2013. View Article : Google Scholar : PubMed/NCBI
13	Wang Z, Liu M, Zhu H, Zhang W, He S, Hu C, Quan L, Bai J and Xu N: miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS. Mol Carcinog. 52:634–646. 2013. View Article : Google Scholar : PubMed/NCBI
14	Xiao B, Guo J, Miao Y, Jiang Z, Huan R, Zhang Y, Li D and Zhong J: Detection of miR-106a in gastric carcinoma and its clinical significance. Clin Chim Acta. 400:97–102. 2009. View Article : Google Scholar : PubMed/NCBI
15	Zhu M, Zhang N, He S, Lui Y, Lu G and Zhao L: MicroRNA-106a targets TIMP2 to regulate invasion and metastasis of gastric cancer. FEBS Lett. 588:600–607. 2014. View Article : Google Scholar : PubMed/NCBI
16	Li P, Xu Q, Zhang D, Li X, Han L, Lei J, Duan W, Ma Q, Wu Z and Wang Z: Upregulated miR-106a plays an oncogenic role in pancreatic cancer. FEBS Lett. 588:705–712. 2014. View Article : Google Scholar : PubMed/NCBI
17	Wang R, Li Y, Hou Y, Yang Q, Chen S, Wang X, Wang Z, Yang Y, Chen C, Wang Z, et al: The PDGF-D/miR-106a/Twist1 pathway orchestrates epithelial-mesenchymal transition in gemcitabine resistance hepatoma cells. Oncotarget. 6:7000–7010. 2015. View Article : Google Scholar : PubMed/NCBI
18	Chen L, Zhang F, Sheng XG, Zhang SQ, Chen YT and Liu BW: MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes the proliferation and invasion of ovarian cancer cells. Oncol Rep. 36:2135–2141. 2016.PubMed/NCBI
19	Zhu M, Zhang N, He S, Yan R and Zhang J: MicroRNA-106a functions as an oncogene in human gastric cancer and contributes to proliferation and metastasis in vitro and in vivo. Clin Exp Metastasis. 33:509–519. 2016. View Article : Google Scholar : PubMed/NCBI
20	Hou X, Zhang M and Qiao H: Diagnostic significance of miR-106a in gastric cancer. Int J Clin Exp Pathol. 8:13096–13101. 2015.PubMed/NCBI
21	Yuan R, Zhi Q, Zhao H, Han Y, Gao L, Wang B, Kou Z, Guo Z, He S, Xue X, et al: Upregulated expression of miR-106a by DNA hypomethylation plays an oncogenic role in hepatocellular carcinoma. Tumour Biol. 36:3093–3100. 2015. View Article : Google Scholar : PubMed/NCBI
22	He QY, Wang GC, Zhang H, Tong DK, Ding C, Liu K, Ji F, Zhu X and Yang S: miR-106a-5p suppresses the proliferation, migration, and invasion of osteosarcoma cells by targeting HMGA2. DNA Cell Biol. 35:506–520. 2016. View Article : Google Scholar : PubMed/NCBI
23	Zhi F, Zhou G, Shao N, Xia X, Shi Y, Wang Q, Zhang Y, Wang R, Xue L, Wang S, et al: miR-106a-5p inhibits the proliferation and migration of astrocytoma cells and promotes apoptosis by targeting FASTK. PLoS One. 8:e723902013. View Article : Google Scholar : PubMed/NCBI
24	Ma Y, Zhang H, He X, Song H, Qiang Y, Li Y, Gao J and Wang Z: miR-106a* inhibits the proliferation of renal carcinoma cells by targeting IRS-2. Tumour Biol. 36:8389–8398. 2015. View Article : Google Scholar : PubMed/NCBI
25	Yang G, Zhang R, Chen X, Mu Y, Ai J, Shi C, Liu Y, Shi C, Sun L, Rainov NG, et al: miR-106a inhibits glioma cell growth by targeting E2F1 independent of p53 status. J Mol Med (Berl). 89:1037–1050. 2011. View Article : Google Scholar : PubMed/NCBI
26	Deng Y, Xiong Y and Liu Y: miR-376c inhibits cervical cancer cell proliferation and invasion by targeting BMI1. Int J Exp Pathol. 97:257–265. 2016. View Article : Google Scholar : PubMed/NCBI
27	Deng B, Zhang Y, Zhang S, Wen F, Miao Y and Guo K: MicroRNA-142-3p inhibits cell proliferation and invasion of cervical cancer cells by targeting FZD7. Tumour Biol. 36:8065–8073. 2015. View Article : Google Scholar : PubMed/NCBI
28	Liu S, Zhang P, Chen Z, Liu M, Li X and Tang H: MicroRNA-7 downregulates XIAP expression to suppress cell growth and promote apoptosis in cervical cancer cells. FEBS Lett. 587:2247–2253. 2013. View Article : Google Scholar : PubMed/NCBI
29	Rothschild SI, Gautschi O, Batliner J, Gugger M, Fey MF and Tschan MP: MicroRNA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors. Lung Cancer. 107:73–83. 2017. View Article : Google Scholar : PubMed/NCBI
30	Servín-González LS, Granados-López AJ and López JA: Families of microRNAs expressed in clusters regulate cell signaling in cervical cancer. Int J Mol Sci. 16:12773–12790. 2015. View Article : Google Scholar : PubMed/NCBI
31	Nagase H and Woessner JF Jr: Matrix metalloproteinases. J Biol Chem. 274:21491–21494. 1999. View Article : Google Scholar : PubMed/NCBI
32	Cardeal LB, Boccardo E, Termini L, Rabachini T, Andreoli MA, di Loreto C, Filho A Longatto, Villa LL and Maria-Engler SS: HPV16 oncoproteins induce MMPs/RECK-TIMP-2 imbalance in primary keratinocytes: Possible implications in cervical carcinogenesis. PLoS One. 7:e335852012. View Article : Google Scholar : PubMed/NCBI
33	Braicu EI, Fotopoulou C, Chekerov R, Richter R, Blohmer J, Kümmel S, Stamatian F, Yalcinkaya I, Mentze M, Lichtenegger W, et al: Role of serum concentration of VEGFR1 and TIMP2 on clinical outcome in primary cervical cancer: Results of a companion protocol of the randomized, NOGGO-AGO phase III adjuvant trial of simultaneous cisplatin-based radiochemotherapy vs. carboplatin and paclitaxel containing sequential radiotherapy. Cytokine. 61:755–758. 2013. View Article : Google Scholar : PubMed/NCBI