Tong Dongdong, Zhao Lingyu, He Kang, Sun Hongfei, Cai Donghui, Ni Lei, Sun Ruifang, Chang Su'e, Song Tusheng, Huang Chen
Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, P. R. China.
Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Shaanxi, P. R. China.
Oncotarget. 2016 Jun 7;7(23):34845-59. doi: 10.18632/oncotarget.9197.
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.
甲基化CpG结合蛋白2（MECP2）是一种转录抑制因子，通过与甲基化启动子结合参与基因调控。我们发现MECP2在胃癌（GC）中过表达，并且敲低Mecp2会影响GC细胞在体外和体内的生长。MECP2可直接结合miR - 338启动子的甲基化CpG岛，并抑制两种成熟微RNA即miR - 338 - 3p和miR - 338 - 5p的表达。此外，miR - 338 - 5p可通过靶向BMI1（B淋巴瘤Mo - MLV插入区域1同源物）来抑制GC细胞生长。我们还发现，相对于正常组织，GC组织中miR - 338 - 5p表达降低与BMI1表达增加显著负相关。沉默MECP2可间接导致P - REX2（已被确定为miR - 338 - 3p的靶点）以及BMI1的表达降低，并在体外和体内增加P16或P21的表达。总之，我们的结果表明，MECP2通过miR - 338（miR - 338 - 3p和miR - 338 - 5p）介导的抗肿瘤和基因调控作用促进GC细胞增殖。
