MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31

Jiang,Chaoyin; Chen,Hua; Shao,Lei; Wang,Qiaojie

doi:10.3892/or.2014.3274

MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31

Authors:
- Chaoyin Jiang
- Hua Chen
- Lei Shao
- Qiaojie Wang
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Affiliations: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
Published online on: June 20, 2014 https://doi.org/10.3892/or.2014.3274
Pages: 1249-1256

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Abstract

MicroRNA-1 (miR-1) has been shown to function as a critical gene regulator in multiple types of cancers. However, the role of miR-1 in osteosarcoma has not been totally clarified. In the present study, we investigated the effects of miR-1 on osteosarcoma and the underlying mechanism. We found that miR-1 was downregulated in osteosarcoma tissues and osteosarcoma cell lines. Restoration of miR-1 significantly suppressed osteosarcoma cell proliferation by inhibiting cell cycle progression. Mediator complex subunit 1 (Med1) and 31 (Med31) were validated as targets of miR-1 in osteosarcoma by luciferase reporter assay. Downregulation of Med1 and Med31 suppressed the proliferation of osteosarcoma cells, and overexpression of Med1 and Med31 abrogated the effects of miR-1 on cell proliferation. Furthermore, both miR-1 and knockdown of Med1 or Med31 reduced the expression of met proto-oncogene (MET) and blocked the downstream signaling of MET responding to hepatocyte growth factor (HGF). Taken together, the findings of this study suggest that Med1 and Med31 serve as potential gene therapeutic targets in osteosarcoma and miR-1 may prove to be a promising agent.

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1	Longhi A, Errani C, De Paolis M, Mercuri M and Bacci G: Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev. 32:423–436. 2006. View Article : Google Scholar : PubMed/NCBI
2	Chou AJ, Geller DS and Gorlick R: Therapy for osteosarcoma: where do we go from here? Paediatr Drugs. 10:315–327. 2008. View Article : Google Scholar : PubMed/NCBI
3	Ferguson WS and Goorin AM: Current treatment of osteosarcoma. Cancer Invest. 19:292–315. 2001. View Article : Google Scholar : PubMed/NCBI
4	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
5	Zhang B, Pan X, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar : PubMed/NCBI
6	Yan K, Gao J, Yang T, et al: MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PLoS One. 7:e337782012. View Article : Google Scholar : PubMed/NCBI
7	Jin Y, Peng D, Shen Y, et al: 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
8	Ji F, Zhang H, Wang Y, et al: MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1. Bone. 56:220–226. 2013. View Article : Google Scholar : PubMed/NCBI
9	Townley-Tilson WH, Callis TE and Wang D: MicroRNAs 1, 133, and 206: critical factors of skeletal and cardiac muscle development, function, and disease. Int J Biochem Cell Biol. 42:1252–1255. 2010. View Article : Google Scholar : PubMed/NCBI
10	Nohata N, Hanazawa T, Enokida H and Seki N: microRNA-1/133a and microRNA-206/133b clusters: dysregulation and functional roles in human cancers. Oncotarget. 3:9–21. 2012.PubMed/NCBI
11	Namlos HM, Meza-Zepeda LA, Baroy T, et al: Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS One. 7:e480862012. View Article : Google Scholar : PubMed/NCBI
12	Novello C, Pazzaglia L, Cingolani C, et al: miRNA expression profile in human osteosarcoma: Role of miR-1 and miR-133b in proliferation and cell cycle control. Int J Oncol. 42:667–675. 2013.PubMed/NCBI
13	Nasser MW, Datta J, Nuovo G, et al: Down-regulation of micro-RNA-1 (miR-1) in lung cancer: suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem. 283:33394–33405. 2008. View Article : Google Scholar : PubMed/NCBI
14	Datta J, Kutay H, Nasser MW, et al: Methylation mediated silencing of microRNA-1 gene and its role in hepatocellular carcinogenesis. Cancer Res. 68:5049–5058. 2008. View Article : Google Scholar : PubMed/NCBI
15	Leone V, D’Angelo D, Rubio I, et al: MiR-1 is a tumor suppressor in thyroid carcinogenesis targeting CCND2, CXCR4, and SDF-1alpha. J Clin Endocrinol Metab. 96:E1388–E1398. 2011. View Article : Google Scholar : PubMed/NCBI
16	Wu CD, Kuo YS, Wu HC and Lin CT: MicroRNA-1 induces apoptosis by targeting prothymosin alpha in nasopharyngeal carcinoma cells. J Biomed Sci. 18:802011. View Article : Google Scholar : PubMed/NCBI
17	Napoli C, Sessa M, Infante T and Casamassimi A: Unraveling framework of the ancestral mediator complex in human diseases. Biochimie. 94:579–587. 2012. View Article : Google Scholar : PubMed/NCBI
18	Matsumoto K, Yu S, Jia Y, et al: Critical role for transcription coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein/TRAP220 in liver regeneration and PPARalpha ligand-induced liver tumor development. J Biol Chem. 282:17053–17060. 2007. View Article : Google Scholar
19	Miao J, Wu S, Peng Z, Tania M and Zhang C: MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects. Tumour Biol. 34:2093–2098. 2013. View Article : Google Scholar : PubMed/NCBI
20	Sarver A, French A, Borralho P, et al: Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer. 9:4012009. View Article : Google Scholar
21	Rao PK, Missiaglia E, Shields L, et al: Distinct roles for miR-1 and miR-133a in the proliferation and differentiation of rhabdomyosarcoma cells. FASEB J. 24:3427–3437. 2010. View Article : Google Scholar : PubMed/NCBI
22	Ansari SA and Morse RH: Mechanisms of mediator complex action in transcriptional activation. Cell Mol Life Sci. 70:2743–2756. 2013. View Article : Google Scholar : PubMed/NCBI
23	Collins SR, Miller KM, Maas NL, et al: Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map. Nature. 446:806–810. 2007. View Article : Google Scholar : PubMed/NCBI
24	Zhang H, Jiang H, Wang W, et al: Expression of Med19 in bladder cancer tissues and its role on bladder cancer cell growth. Urol Oncol. 30:920–927. 2012. View Article : Google Scholar : PubMed/NCBI
25	Yoon NK, Maresh EL, Elshimali Y, et al: Elevated MED28 expression predicts poor outcome in women with breast cancer. BMC Cancer. 10:3352010. View Article : Google Scholar : PubMed/NCBI
26	Schiano C, Rienzo M, Casamassimi A and Napoli C: Gene expression profile of the whole mediator complex in human osteosarcoma and normal osteoblasts. Med Oncol. 30:7392013. View Article : Google Scholar : PubMed/NCBI
27	Gade P, Singh AK, Roy SK, Reddy SP and Kalvakolanu DV: Down-regulation of the transcriptional mediator subunit Med1 contributes to the loss of expression of metastasis-associated dapk1 in human cancers and cancer cells. Int J Cancer. 125:1566–1574. 2009. View Article : Google Scholar : PubMed/NCBI
28	de Ndong JL, Jean D, Rousselet N and Frade R: Down-regulation of the expression of RB18A/MED1, a cofactor of transcription, triggers strong tumorigenic phenotype of human melanoma cells. Int J Cancer. 124:2597–2606. 2009.PubMed/NCBI
29	Matsumoto K, Huang J, Viswakarma N, et al: Transcription coactivator PBP/MED1-deficient hepatocytes are not susceptible to diethylnitrosamine-induced hepatocarcinogenesis in the mouse. Carcinogenesis. 31:318–325. 2010. View Article : Google Scholar : PubMed/NCBI
30	Vijayvargia R, May MS and Fondell JD: A coregulatory role for the mediator complex in prostate cancer cell proliferation and gene expression. Cancer Res. 67:4034–4041. 2007. View Article : Google Scholar : PubMed/NCBI
31	Risley MD, Clowes C, Yu M, Mitchell K and Hentges KE: The mediator complex protein Med31 is required for embryonic growth and cell proliferation during mammalian development. Dev Biol. 342:146–156. 2010. View Article : Google Scholar : PubMed/NCBI
32	Gao CF and Woude GF: HGF/SF-Met signaling in tumor progression. Cell Res. 15:49–51. 2005. View Article : Google Scholar : PubMed/NCBI