MicroRNA‑320 inhibits cell proliferation and invasion in breast cancer cells by targeting SOX4

Bai,Jun‑Wen; Wang,Xia; Zhang,Ya‑Feng; Yao,Guo‑Dong; Liu,Hong

doi:10.3892/ol.2017.7087

MicroRNA‑320 inhibits cell proliferation and invasion in breast cancer cells by targeting SOX4

Authors:
- Jun‑Wen Bai
- Xia Wang
- Ya‑Feng Zhang
- Guo‑Dong Yao
- Hong Liu
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Affiliations: The Second Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Department of Surgery, Affiliated Hospital of Inner Mongolia Medical University, Huhhot, Inner Mongolia Autonomous Region 010050, P.R. China
Published online on: September 27, 2017 https://doi.org/10.3892/ol.2017.7087
Pages: 7145-7152
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dysregulation of microRNAs (miRs) can contribute to cancer development and progression. In the present study, the function and underlying molecular mechanisms of miR‑320 in breast cancer tumorigenesis and progression were investigated. The results of a reverse transcription‑quantitative polymerase chain reaction analysis demonstrated that miR‑320 was frequently downregulated in breast cancer tissues compared with adjacent normal tissues. In addition, knockdown of miR‑320 in breast cancer cell lines promoted cell proliferation and invasion in vitro, whereas miR‑320 overexpression had the opposite effect. Furthermore, a Dual‑Luciferase reporter assay indicated that SRY‑box 4 (SOX4) is a direct target of miR‑320, and the restoration of SOX4 in miR‑320‑overexpressing cells attenuated the tumor‑suppressive effects of miR‑320. Collectively, these results indicated that miR‑320 acts as a tumor suppressor in breast cancer tumorigenesis and progression.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Karlsson MC, Gonzalez SF, Welin J and Fuxe J: Epithelial-mesenchymal transition in cancer metastasis through the lymphatic system. Mol Oncol. 11:781–791. 2017. View Article : Google Scholar : PubMed/NCBI
3	Poncy A, Antoniou A, Cordi S, Pierreux CE, Jacquemin P and Lemaigre FP: Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts. Dev Biol. 404:136–148. 2015. View Article : Google Scholar : PubMed/NCBI
4	Jang SM, Kim JW, Kim CH, An JH, Johnson A, Song PI, Rhee S and Choi KH: KAT5-mediated SOX4 acetylation orchestrates chromatin remodeling during myoblast differentiation. Cell Death Dis. 6:e18572015. View Article : Google Scholar : PubMed/NCBI
5	Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, Meyer-Schaller N, Schübeler D, van Nimwegen E and Christofori G: Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell. 23:768–783. 2013. View Article : Google Scholar : PubMed/NCBI
6	Wang B, Li Y, Tan F and Xiao Z: Increased expression of SOX4 is associated with colorectal cancer progression. Tumour Biol. 37:9131–9137. 2016. View Article : Google Scholar : PubMed/NCBI
7	Bilir B, Osunkoya AO, Wiles WG IV, Sannigrahi S, Lefebvre V, Metzger D, Spyropoulos DD, Martin WD and Moreno CS: SOX4 is essential for prostate tumorigenesis initiated by PTEN ablation. Cancer Res. 76:1112–1121. 2016. View Article : Google Scholar : PubMed/NCBI
8	Hasegawa S, Nagano H, Konno M, Eguchi H, Tomokuni A, Tomimaru Y, Asaoka T, Wada H, Hama N, Kawamoto K, et al: A crucial epithelial to mesenchymal transition regulator, Sox4/Ezh2 axis is closely related to the clinical outcome in pancreatic cancer patients. Int J Oncol. 48:145–152. 2016. View Article : Google Scholar : PubMed/NCBI
9	Sung WJ, Kim H and Park KK: The biological role of epithelial-mesenchymal transition in lung cancer (Review). Oncol Rep. 36:1199–1206. 2016. View Article : Google Scholar : PubMed/NCBI
10	Zhang J, Liang Q, Lei Y, Yao M, Li L, Gao X, Feng J, Zhang Y, Gao H, Liu DX, et al: SOX4 induces epithelial-mesenchymal transition and contributes to breast cancer progression. Cancer Res. 72:4597–4608. 2012. View Article : Google Scholar : PubMed/NCBI
11	Sinner D, Kordich JJ, Spence JR, Opoka R, Rankin S, Lin SC, Jonatan D, Zorn AM and Wells JM: Sox17 and Sox4 differentially regulate beta-catenin/T-cell factor activity and proliferation of colon carcinoma cells. Mol Cell Biol. 27:7802–7815. 2007. View Article : Google Scholar : PubMed/NCBI
12	Jiao C, Song Z, Chen J, Zhong J, Cai W, Tian S, Chen S, Yi Y and Xiao Y: lncRNA-UCA1 enhances cell proliferation through functioning as a ceRNA of Sox4 in esophageal cancer. Oncol Rep. 36:2960–2966. 2016. View Article : Google Scholar : PubMed/NCBI
13	Wang W, Zhang E and Lin C: MicroRNAs in tumor angiogenesis. Life Sci. 136:28–35. 2015. View Article : Google Scholar : PubMed/NCBI
14	Huang J, Zhang SY, Gao YM, Liu YF, Liu YB, Zhao ZG and Yang K: MicroRNAs as oncogenes or tumour suppressors in oesophageal cancer: Potential biomarkers and therapeutic targets. Cell Prolif. 47:277–286. 2014. View Article : Google Scholar : PubMed/NCBI
15	Kim VN, Han J and Siomi MC: Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 10:126–139. 2009. View Article : Google Scholar : PubMed/NCBI
16	Thomson DW, Bracken CP and Goodall GJ: Experimental strategies for microRNA target identification. Nucleic Acids Res. 39:6845–6853. 2011. View Article : Google Scholar : PubMed/NCBI
17	Rupaimoole R, Calin GA, Lopez-Berestein G and Sood AK: miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov. 6:235–246. 2016. View Article : Google Scholar : PubMed/NCBI
18	Magee P, Shi L and Garofalo M: Role of microRNAs in chemoresistance. Ann Transl Med. 3:3322015.PubMed/NCBI
19	Yin K, Yin W, Wang Y, Zhou L, Liu Y, Yang G, Wang J and Lu J: MiR-206 suppresses epithelial mesenchymal transition by targeting TGF-β signaling in estrogen receptor positive breast cancer cells. Oncotarget. 7:24537–24548. 2016. View Article : Google Scholar : PubMed/NCBI
20	Yu Y, Zhao Y, Sun XH, Ge J, Zhang B, Wang X and Cao XC: Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial-mesenchymal transition and is associated with poor prognosis in breast cancer. Oncotarget. 6:34423–34436. 2015.PubMed/NCBI
21	Rhodes LV, Martin EC, Segar HC, Miller DF, Buechlein A, Rusch DB, Nephew KP, Burow ME and Collins-Burow BM: Dual regulation by microRNA-200b-3p and microRNA-200b-5p in the inhibition of epithelial-to-mesenchymal transition in triple-negative breast cancer. Oncotarget. 6:16638–16652. 2015. View Article : Google Scholar : PubMed/NCBI
22	Yang S, Li Y, Gao J, Zhang T, Li S, Luo A, Chen H, Ding F, Wang X and Liu Z: MicroRNA-34 suppresses breast cancer invasion and metastasis by directly targeting Fra-1. Oncogene. 32:4294–4303. 2013. View Article : Google Scholar : PubMed/NCBI
23	Pichler M and Calin GA: MicroRNAs in cancer: From developmental genes in worms to their clinical application in patients. Br J Cancer. 113:569–573. 2015. View Article : Google Scholar : PubMed/NCBI
24	Wan LY, Deng J, Xiang XJ, Zhang L, Yu F, Chen J, Sun Z, Feng M and Xiong JP: miR-320 enhances the sensitivity of human colon cancer cells to chemoradiotherapy in vitro by targeting FOXM1. Biochem Biophys Res Commun. 457:125–132. 2015. View Article : Google Scholar : PubMed/NCBI
25	Zhang T, Zou P, Wang T, Xiang J, Cheng J, Chen D and Zhou J: Down-regulation of miR-320 associated with cancer progression and cell apoptosis via targeting Mcl-1 in cervical cancer. Tumour Biol. 37:8931–8940. 2016. View Article : Google Scholar : PubMed/NCBI
26	Sun JY, Xiao WZ, Wang F, Wang YQ, Zhu YH, Wu YF, Miao ZL and Lin YC: MicroRNA-320 inhibits cell proliferation in glioma by targeting E2F1. Mol Med Rep. 12:2355–2359. 2015. View Article : Google Scholar : PubMed/NCBI
27	Hsieh IS, Chang KC, Tsai YT, Ke JY, Lu PJ, Lee KH, Yeh SD, Hong TM and Chen YL: MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway. Carcinogenesis. 34:530–538. 2013. View Article : Google Scholar : PubMed/NCBI
28	Wu YY, Chen YL, Jao YC, Hsieh IS, Chang KC and Hong TM: miR-320 regulates tumor angiogenesis driven by vascular endothelial cells in oral cancer by silencing neuropilin 1. Angiogenesis. 17:247–260. 2014. View Article : Google Scholar : PubMed/NCBI
29	Vishnubalaji R, Hamam R, Yue S, Al-Obeed O, Kassem M, Liu FF, Aldahmash A and Alajez NM: MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1. Oncotarget. 7:35789–35802. 2016. View Article : Google Scholar : PubMed/NCBI
30	Lakhani SR, Ellis IO, Schnitt SJ, Tan PH and van de Vijver MJ: WHO Classification of Tumours of the Breast. 4th edition. Lyon: IARC Press; 2012
31	Zhang YF, Yu Y, Song WZ, Zhang RM, Jin S, Bai JW, Kang HB, Wang X and Cao XC: miR-410-3p suppresses breast cancer progression by targeting Snail. Oncol Rep. 36:480–486. 2016. View Article : Google Scholar : PubMed/NCBI
32	Betel D, Wilson M, Gabow A, Marks DS and Sander C: The microRNA.org resource: Targets and expression. Nucleic Acids Res. 36:(Database Issue). D149–D153. 2008. View Article : Google Scholar : PubMed/NCBI
33	Adlakha YK and Saini N: MicroRNA: A connecting road between apoptosis and cholesterol metabolism. Tumour Biol. 37:8529–8554. 2016. View Article : Google Scholar : PubMed/NCBI
34	Chen Y, Yang X, Xu Y, Cao J and Chen L: Genomic analysis of drug resistant small cell lung cancer cell lines by combining mRNA and miRNA expression profiling. Oncol Lett. 13:4077–4084. 2017.PubMed/NCBI
35	Macedo T, Silva-Oliveira RJ, Silva VAO, Vidal DO, Evangelista AF and Marques MMC: Overexpression of mir-183 and mir-494 promotes proliferation and migration in human breast cancer cell lines. Oncol Lett. 14:1054–1060. 2017.PubMed/NCBI
36	Cheng C, Chen ZQ and Shi XT: MicroRNA-320 inhibits osteosarcoma cells proliferation by directly targeting fatty acid synthase. Tumour Biol. 35:4177–4183. 2014. View Article : Google Scholar : PubMed/NCBI
37	Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX and Shao JY: MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 14:2348–2360. 2008. View Article : Google Scholar : PubMed/NCBI
38	Wang B, Yang Z, Wang H, Cao Z, Zhao Y, Gong C, Ma L, Wang X, Hu X and Chen S: MicroRNA-320a inhibits proliferation and invasion of breast cancer cells by targeting RAB11A. Am J Cancer Res. 5:2719–2729. 2015. View Article : Google Scholar : PubMed/NCBI
39	Jin Y, Zhao M, Xie Q, Zhang H, Wang Q and Ma Q: MicroRNA-338-3p functions as tumor suppressor in breast cancer by targeting SOX4. Int J Oncol. 47:1594–1602. 2015. View Article : Google Scholar : PubMed/NCBI
40	Liu Y, Li Y, Liu J, Wu Y and Zhu Q: MicroRNA-132 inhibits cell growth and metastasis in osteosarcoma cell lines possibly by targeting Sox4. Int J Oncol. 47:1672–1684. 2015. View Article : Google Scholar : PubMed/NCBI