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Down-regulation of miR-212 expression by DNA hypermethylation in human gastric cancer cells

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Abstract

There has been few report discussing the expression and function of miR-212 in gastric cancer (GC). The aim of this pilot study was to investigate the expression of miR-212 in both gastric cancer tissues and gastric cancer cells and further explores the possible reasons for this change and the impact on the development of gastric cancer. qRT–PCR was used to detect the expression of miR-212 in primary GC tissues, adjacent normal tissues, gastric cancer cell lines BGC-823, SGC-7901, MKN-45, and normal gastric mucosa cell line GES. The expression of miR-212 was evaluated before and after treatment with methylation inhibitor-5-Aza-2′-deoxycitidine (5-Aza-dC), finally anti-miRNA and dual luciferase reporter assay were used to prove that MYC is a target gene of miR-212. The results showed that a significant reduction of miR-212 expression in GC tissues was observed compared to that in normal tissues (P = 0.002). At the same time, miR-212 expression level in normal gastric mucosa cell line GES was higher than that of in gastric cancer cell lines BGC-823, SGC-7901, and MKN-45 (P = 0.015, 0.008, 0.044, respectively). Computer sequence analysis showed the hypermethylation of CpG islands(CPI) in the promoter regions of miR-212 led to the lower expression of miR-212 in gastric cell strains (BGC-823 and SGC-7901). MiR-212 expression was significantly recovered after treatment with methylation inhibitor 5-Aza-dC (P = 0.016, 0.000, 0.015, respectively). Then, the results of AMOs transfection and dual luciferase reporter assay showed that Myc is a target of miR-212, which will be helpful to verify the function of miR-212 in carcinogenesis. The conclusion could be deduced from the study that decreased expression of miR-212 may be due to hypermethylation of CPI in gastric cancer cells, and miR-212 might act on the progression of gastric cancer through the potential target gene Myc.

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Acknowledgments

We thank Miss Yong Hua for excellent advice and critical reading of this paper.

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  1. Department of Gastroenterology, Tenth People’s Hospital of Tongji University, Shanghai, 200072, China

    Ling Xu, Feng Wang, Xuan-Fu Xu, Wen-Hui Mo, Yu-Jing Xia, Rong Wan, Xing-Peng Wang & Chuan-Yong Guo

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  1. Ling Xu
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Correspondence to Chuan-Yong Guo.

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Xu, L., Wang, F., Xu, XF. et al. Down-regulation of miR-212 expression by DNA hypermethylation in human gastric cancer cells. Med Oncol 28 (Suppl 1), 189–196 (2011). https://doi.org/10.1007/s12032-010-9691-0

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  • DOI: https://doi.org/10.1007/s12032-010-9691-0

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