Overexpression of miR-422a inhibits cell proliferation and invasion, and enhances chemosensitivity in osteosarcoma cells

Liu,Mingjiang; Xiusheng,He; Xiao,Xiangjun; Wang,Yichun

doi:10.3892/or.2016.5182

Overexpression of miR-422a inhibits cell proliferation and invasion, and enhances chemosensitivity in osteosarcoma cells

Authors:
- Mingjiang Liu
- He Xiusheng
- Xiangjun Xiao
- Yichun Wang
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Affiliations: Department of Hand Surgery, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, P.R. China, Cancer Research Institute, University of South China, Hengyang, Hunan 421002, P.R. China, Department of ICU, Hunan Cancer Hospital, Changsha, Hunan 410013, P.R. China
Published online on: October 19, 2016 https://doi.org/10.3892/or.2016.5182
Pages: 3371-3378

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Abstract

Osteosarcoma (OS) is an aggressive malignant tumor that is mesenchymal in origin with a very low 5-year survival rate, particularly in the patients with locally advanced or metastatic tumors and recurrent disease. MicroRNAs (miRNAs) play a critical role in essential biological processes as cellular proliferation, differentiation and apoptosis in normal or cancer cells, including OS cells. In the present study, we aimed to investigate the role of miR-422a in OS. We demonstrated that miR-422a expression was significantly downregulated in OS tissues and cell lines compared with the normal controls. In addition, overexpression of miR-422a was able to inhibit cell proliferation and the ability of invasion, and enhance paclitaxel and cisplatin-mediated apoptosis in OS cells. Inversely, downregulation of miR-422a exhibited an opposite role. We further demonstrated that miR-422a directly targeted TGFβ2 and regulated its expression and the activation of downstream molecules, smad2 and smad3 in OS cells. Thus, miR-422a/TGFβ2/smad axis may be a potential target for OS treatment.

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1	Sampson VB, Yoo S, Kumar A, Vetter NS and Kolb EA: MicroRNAs and potential targets in osteosarcoma: Review. Front Pediatr. 3:692015. View Article : Google Scholar : PubMed/NCBI
2	Lim HJ and Yang JL: Regulatory roles and therapeutic potential of microRNA in sarcoma. Crit Rev Oncol Hematol. 97:118–130. 2016. View Article : Google Scholar : PubMed/NCBI
3	Varshney J and Subramanian S: MicroRNAs as potential target in human bone and soft tissue sarcoma therapeutics. Front Mol Biosci. 2:312015. View Article : Google Scholar : PubMed/NCBI
4	Zhou G, Shi X, Zhang J, Wu S and Zhao J: MicroRNAs in osteosarcoma: From biological players to clinical contributors, a review. J Int Med Res. 41:1–12. 2013. View Article : Google Scholar : PubMed/NCBI
5	Zhou W, Hao M, Du X, Chen K, Wang G and Yang J: Advances in targeted therapy for osteosarcoma. Discov Med. 17:301–307. 2014.PubMed/NCBI
6	Zhang J, Yan YG, Wang C, Zhang SJ, Yu XH and Wang WJ: MicroRNAs in osteosarcoma. Clin Chim Acta. 444:9–17. 2015. View Article : Google Scholar : PubMed/NCBI
7	Zhang LQ, Sun SL, Li WY, Feng Z, Xu XY, Zhuang QS and Fang J: Decreased expression of tumor suppressive miR-874 and its clinical significance in human osteosarcoma. Genet Mol Res. 14:18315–18324. 2015. View Article : Google Scholar : PubMed/NCBI
8	Zhou S, Wang B, Hu J, Zhou Y, Jiang M, Wu M, Qin L and Yang X: miR-421 is a diagnostic and prognostic marker in patients with osteosarcoma. Tumour Biol. Jan 13–2016.(Epub ahead of print).
9	Niu G, Li B, Sun L and An C: MicroRNA-153 inhibits osteosarcoma cells proliferation and invasion by targeting TGF-β2. PLoS One. 10:e01192252015. View Article : Google Scholar : PubMed/NCBI
10	Zhang J, Yang Y, Yang T, Yuan S, Wang R, Pan Z, Yang Y, Huang G, Gu F, Jiang B, et al: Double-negative feedback loop between microRNA-422a and forkhead box (FOX)G1/Q1/E1 regulates hepatocellular carcinoma tumor growth and metastasis. Hepatology. 61:561–573. 2015. View Article : Google Scholar : PubMed/NCBI
11	Gougelet A, Pissaloux D, Besse A, Perez J, Duc A, Dutour A, Blay JY and Alberti L: Micro-RNA profiles in osteosarcoma as a predictive tool for ifosfamide response. Int J Cancer. 129:680–690. 2011. View Article : Google Scholar : PubMed/NCBI
12	Bahador R, Taheriazam A, Mirghasemi A, Torkaman A, Shakeri M, Yahaghi E and Goudarzi PK: Tissue expression levels of miR-29b and miR-422a in children, adolescents, and young adults' age groups and their association with prediction of poor prognosis in human osteosarcoma. Tumour Biol. 37:3091–3095. 2016. View Article : Google Scholar : PubMed/NCBI
13	Faltejskova P, Svoboda M, Srutova K, Mlcochova J, Besse A, Nekvindova J, Radova L, Fabian P, Slaba K, Kiss I, et al: Identification and functional screening of microRNAs highly deregulated in colorectal cancer. J Cell Mol Med. 16:2655–2666. 2012. View Article : Google Scholar : PubMed/NCBI
14	Wang L, Liu M, Zhu H, Rong W, Wu F, An S, Liu F, Feng L, Wu J and Xu N: Identification of recurrence-related serum microRNAs in hepatocellular carcinoma following hepatectomy. Cancer Biol Ther. 16:1445–1452. 2015. View Article : Google Scholar : PubMed/NCBI
15	Qin YZ, Xie XC, Liu HZ, Lai H, Qiu H and Ge LY: Screening and preliminary validation of miRNAs with the regulation of hTERT in colorectal cancer. Oncol Rep. 33:2728–2736. 2015.PubMed/NCBI
16	Zheng G, Du L, Yang X, Zhang X, Wang L, Yang Y, Li J and Wang C: Serum microRNA panel as biomarkers for early diagnosis of colorectal adenocarcinoma. Br J Cancer. 111:1985–1992. 2014. View Article : Google Scholar : PubMed/NCBI
17	Liang S, Chen L, Huang H and Zhi D: The experimental study of miRNA in pituitary adenomas. Turk Neurosurg. 23:721–727. 2013.PubMed/NCBI
18	Won KY, Kim YW and Park YK: Expression of Smad and its signalling cascade in osteosarcoma. Pathology. 42:242–247. 2010. View Article : Google Scholar : PubMed/NCBI
19	Johnsen SA, Subramaniam M, Janknecht R and Spelsberg TC: TGFbeta inducible early gene enhances TGFbeta/Smad-dependent transcriptional responses. Oncogene. 21:5783–5790. 2002. View Article : Google Scholar : PubMed/NCBI
20	Zaidi SK, Sullivan AJ, van Wijnen AJ, Stein JL, Stein GS and Lian JB: Integration of Runx and Smad regulatory signals at transcriptionally active subnuclear sites. Proc Natl Acad Sci USA. 99:8048–8053. 2002. View Article : Google Scholar : PubMed/NCBI
21	Nikitovic D, Zafiropoulos A, Katonis P, Tsatsakis A, Theocharis AD, Karamanos NK and Tzanakakis GN: Transforming growth factor-beta as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase-2 and synthesis of hyaluronan in malignant osteosarcoma cells. IUBMB Life. 58:47–53. 2006. View Article : Google Scholar : PubMed/NCBI
22	Nikitovic D, Chalkiadaki G, Berdiaki A, Aggelidakis J, Katonis P, Karamanos NK and Tzanakakis GN: Lumican regulates osteosarcoma cell adhesion by modulating TGFβ2 activity. Int J Biochem Cell Biol. 43:928–935. 2011. View Article : Google Scholar : PubMed/NCBI
23	Ren XF, Mu LP, Jiang YS, Wang L and Ma JF: LY2109761 inhibits metastasis and enhances chemosensitivity in osteosarcoma MG-63 cells. Eur Rev Med Pharmacol Sci. 19:1182–1190. 2015.PubMed/NCBI
24	Xu S, Yang S, Sun G, Huang W and Zhang Y: Transforming growth factor-beta polymorphisms and serum level in the development of osteosarcoma. DNA Cell Biol. 33:802–806. 2014. View Article : Google Scholar : PubMed/NCBI