Demethylation of microRNA-142 induced by demethylation agents plays a suppressive role in osteosarcoma cells

Ding,Muliang; Hu,Jianzhong; Ni,Jiangdong; Zheng,Zhonghui; Song,Deye; Wang,Junjie

doi:10.3892/ol.2015.3036

Demethylation of microRNA-142 induced by demethylation agents plays a suppressive role in osteosarcoma cells

Authors:
- Muliang Ding
- Jianzhong Hu
- Jiangdong Ni
- Zhonghui Zheng
- Deye Song
- Junjie Wang
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Affiliations: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: March 13, 2015 https://doi.org/10.3892/ol.2015.3036
Pages: 2261-2267

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Abstract

Osteosarcoma (OS), the most common malignant bone tumor, occurs mainly in adolescents and young adults, with a morbidity of ~5 cases per million. The expression levels of microRNAs (miRNAs) as tumor suppressors were recently found to be downregulated in OS. Certain alterations of miRNAs and the possible mechanisms through which miRNAs affect cell proliferation and migration in OS were recently found to be correlated with methylation epigenetic mechanisms. In this study, it was demonstrated that, due to hypermethylation, the expression level of miRNA‑142 (miR‑142) was significantly downregulated in OS tissues and cells compared with that in control samples. The present study demonstrated an increased expression of miR‑142 in Saos‑2 and MG63 cells treated with demethylation agents, suggesting that the effect of such agents on cell growth, inhibition of invasion and cell cycle retardation may be mediated by miR‑142 in OS.

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1	Kobayashi E, Hornicek FJ and Duan Z: MicroRNA involvement in osteosarcoma. Sarcoma. 2012.3597392012.PubMed/NCBI
2	Cao ZQ, Shen Z and Huang WY: MicroRNA-802 promotes osteosarcoma cell proliferation by targeting p27. Asian Pac J Cancer Prev. 14:7081–7084. 2013. View Article : Google Scholar : PubMed/NCBI
3	Diao CY, Guo HB, Ouyang YR, et al: Screening for metastatic osteosarcoma biomarkers with a DNA microarray. Asian Pac J Cancer Prev. 15:1817–1822. 2014. View Article : Google Scholar : PubMed/NCBI
4	Benavente CA, McEvoy JD, Finkelstein D, et al: Cross-speciesgenomic and epigenomic landscape of retinoblastoma. Oncotarget. 4:844–859. 2013.PubMed/NCBI
5	Jin J, Cai L, Liu ZM and Zhou XS: miRNA-218 inhibits osteosarcoma cellmigration and invasion by down-regulating of TIAM1, MMP2 and MMP9. Asian Pac J Cancer Prev. 14:3681–3684. 2013. View Article : Google Scholar : PubMed/NCBI
6	Maire G, Martin JW, Yoshimoto M, Chilton-MacNeill S, Zielenska M and Squire JA: Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma. Cancer Genet. 204:138–146. 2011. View Article : Google Scholar : PubMed/NCBI
7	Lewis BP, Burge CB and Bartel DP: Conserved seedpairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
8	Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 10:704–714. 2009. View Article : Google Scholar : PubMed/NCBI
9	Kelly TK, De Carvalho DD and Jones PA: Epigenetic modifications as therapeutic targets. Nat Biotechnol. 28:1069–1078. 2010. View Article : Google Scholar : PubMed/NCBI
10	Jones KB, Salah Z, Del Mare S, et al: miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 72:1865–1877. 2012. View Article : Google Scholar : PubMed/NCBI
11	Poos K, Smida J, Nathrath M, Maugg D, Baumhoer D and Korsching E: HowmicroRNA and transcription factor co-regulatory networks affect osteosarcoma cell proliferation. PLoS Comput Biol. 9:e10032102013. View Article : Google Scholar : PubMed/NCBI
12	Png KJ, Yoshida M, Zhang XH, et al: MicroRNA-335 inhibits tumorreinitiation and is silenced throughgenetic and epigenetic mechanisms in human breast cancer. Genes Dev. 25:226–231. 2011. View Article : Google Scholar : PubMed/NCBI
13	Das S, Bryan K, Buckley PG, et al: Modulation of neuroblastoma disease pathogenesis by an extensive network of epigenetically regulated microRNAs. Oncogene. 32:2927–2936. 2013. View Article : Google Scholar : PubMed/NCBI
14	He C, Xiong J, Xu X, et al: Functional elucidation of MiR-34 in osteosarcomacells and primary tumor samples. Biochem Biophys Res Commun. 388:35–40. 2009. View Article : Google Scholar : PubMed/NCBI
15	Qian S, Ding JY, Xie R, et al: MicroRNA expression profile of bronchioalveolar stem cells from mouse lung. Biochem Biophys Res Commun. 377:668–673. 2008. View Article : Google Scholar : PubMed/NCBI
16	Lin RJ, Xiao DW, Liao LD, et al: MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma. J Surg Oncol. 105:175–182. 2012. View Article : Google Scholar : PubMed/NCBI
17	Namløs HM, Meza-Zepeda LA, Barøy T, et al: Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS One. 7:e480862012. View Article : Google Scholar : PubMed/NCBI
18	Posthuma De Boer J, Witlox MA, Kaspers GJ and van Royen BJ: Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature. Clin Exp Metastasis. 28:493–503. 2011. View Article : Google Scholar : PubMed/NCBI
19	Baumhoer D, Zillmer S, Unger K, et al: MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma. Cancer Genet. 205:212–219. 2012. View Article : Google Scholar : PubMed/NCBI
20	Lulla RR, Costa FF, Bischof JM, et al: Identification of differentially expressed microRNAs in osteosarcoma. Sarcoma. 2011.7326902011.PubMed/NCBI
21	Boeri M, Verri C, Conte D, et al: MicroRNA signatures intissues and plasma predictdevelopment and prognosis of computed tomography detected lung cancer. In: Proc Natl Acad Sci USA. 108. pp. 3713–3718. 2011; View Article : Google Scholar : PubMed/NCBI
22	Kaduthanam S, Gade S, Meister M, et al: Serum miR-142-3p is associated with early relapse in operable lung adenocarcinoma patients. Lung Cancer. 80:223–227. 2013. View Article : Google Scholar : PubMed/NCBI
23	Lei Z, Xu G, Wang L, et al: MiR-142-3p represses TGF-β-induced growth inhibition through repression of TGFβR1 in non-small cell lung cancer. FASEB J. 28:2696–2704. 2014. View Article : Google Scholar : PubMed/NCBI
24	Wang XY, Wu MH, Liu F, et al: Differential miRNAexpression and their target genes between NGX6-positive and negative colon cancer cells. Mol Cell Biochem. 345:283–290. 2010. View Article : Google Scholar : PubMed/NCBI
25	Shen WW, Zeng Z, Zhu WX and Fu GH: MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells. J Mol Med (Berl). 91:989–1000. 2013. View Article : Google Scholar : PubMed/NCBI
26	Lee Y, Ahn C, Han J, et al: The nuclear RNase III Drosha initiates microRNA processing. Nature. 425:415–419. 2003. View Article : Google Scholar : PubMed/NCBI
27	Lee Y, Jeon K, Lee JT, Kim S and Kim VN: MicroRNA maturation: stepwiseprocessing and subcellular localization. EMBO J. 21:4663–4670. 2002. View Article : Google Scholar : PubMed/NCBI
28	Vrba L, Garbe JC, Stampfer MR and Futscher BW: Epigenetic regulation of normal human mammary cell type-specific miRNAs. Genome Res. 21:2026–2037. 2011. View Article : Google Scholar : PubMed/NCBI
29	Hackett JA and Surani MA: DNA methylation dynamics during the mammalian life cycle. Philos Trans R Soc Lond B Biol Sci. 368:201103282013. View Article : Google Scholar : PubMed/NCBI
30	Weber B, Stresemann C, Brueckner B and Lyko F: Methylation of human microRNA genes innormal and neoplastic cells. Cell Cycle. 6:1001–1005. 2007. View Article : Google Scholar : PubMed/NCBI
31	Bissels U, Wild S, Tomiuk S, et al: Combined characterization ofmicroRNA and mRNA profiles delineates early differentiation pathways of CD133⁺ and CD34⁺ hematopoieticstem and progenitor cells. Stem Cells. 29:847–857. 2011. View Article : Google Scholar : PubMed/NCBI
32	Wu L, Cai C, Wang X, Liu M, Li X and Tang H: MicroRNA-142-3p, a new regulator of RAC1, suppresses themigration and invasion of hepatocellular carcinoma cells. FEBS Lett. 585:1322–1330. 2011. View Article : Google Scholar : PubMed/NCBI
33	Zhang P, Bill K, Liu J, et al: MiR-155 is a liposarcoma oncogene that targets casein kinase-1α and enhances β-catenin signaling. Cancer Res. 72:1751–1762. 2012. View Article : Google Scholar : PubMed/NCBI