MECP2 promotes the growth of gastric cancer cells by suppressing miR-338-mediated antiproliferative effect
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Dongdong Tong1,2, Lingyu Zhao1,2, Kang He1,2,3, Hongfei Sun1,2, Donghui Cai1,2, Lei Ni1, Ruifang Sun4, Su’e Chang5, Tusheng Song1,2, Chen Huang1,2
1Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, P. R. China
2Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China, Shaanxi, P. R. China
3Department of Periodontology, Stomatology Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, P. R. China
4Department of pathology, College of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, P. R. China
5Department of Orthopaedics, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, P. R. China
Chen Huang, email: [email protected]
Keywords: gastric cancer, MECP2, miR-338, BMI1, proliferation
Received: October 19, 2015 Accepted: March 31, 2016 Published: May 06, 2016
The methyl-CpG-binding protein 2 (MECP2), a transcriptional suppressor, is involved in gene regulation by binding to methylated promoters. We found that MECP2 is overexpressed in gastric cancer (GC), and that Mecp2 knockdown affects the growth of GC cells both in vitro and in vivo. MECP2 can directly bind to the methylated-CpG island of miR-338 promoter and suppress the expression of two mature microRNAs, namely, miR-338-3p and miR-338-5p. Furthermore, miR-338-5p can suppress GC cell growth by targeting BMI1 (B lymphoma Mo-MLV insertion region 1 homolog). We additionally found that decreased miR-338-5p expression in GC tissues, relative to normal tissues, was significantly negatively correlated with increased BMI1 expression. Silencing MECP2 can indirectly lead to reduced expression of P-REX2, which has been identified as the miR-338-3p target, as well as BMI1 and increasing expression of P16 or P21 both in vitro and in vivo. Altogether, our results indicate that MECP2 promote the proliferation of GC cells via miR-338 (miR-338-3p and miR-338-5p)-mediated antitumor and gene regulatory effect.
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