MicroRNA-195 and microRNA-378 mediate tumor growth suppression by epigenetical regulation in gastric cancer

被引：148
作者：
Deng, Hongxia [1 ,2 ]
Guo, Yanan [1 ,2 ]
Song, Haojun [1 ,2 ]
Xiao, Bingxiu [1 ,2 ]
Sun, Weiliang [3 ,4 ]
Liu, Zhong [5 ]
Yu, Xiuchong [1 ,2 ]
Xia, Tian [1 ,2 ]
Cui, Long [1 ,2 ]
Guo, Junming [1 ,2 ]
机构：
[1] Ningbo Univ, Sch Med, Dept Biochem & Mol Biol, Ningbo 315211, Zhejiang, Peoples R China
[2] Ningbo Univ, Sch Med, Zhejiang Prov Key Lab Pathophysiol, Ningbo 315211, Zhejiang, Peoples R China
[3] Ningbo Univ, Sch Med, Ningbo Yinzhou Peoples Hosp, Ningbo 315040, Zhejiang, Peoples R China
[4] Ningbo Univ, Sch Med, Affiliated Hosp, Ningbo 315040, Zhejiang, Peoples R China
[5] Ningbo Univ, Sch Med, Affiliated Hosp, Ningbo 315010, Zhejiang, Peoples R China
来源：
GENE | 2013年 / 518卷 / 02期
基金：
中国国家自然科学基金;
关键词：
MicroRNA; Gastric cancer; Tumor suppressor; Cell cycle; Epigenetic; CELL-CYCLE PROGRESSION; DNA METHYLATION; DOWN-REGULATION; SMALL RNA; EXPRESSION; PROLIFERATION; CARCINOMA; TRANSITION; GENE; VEGF;
D O I：
10.1016/j.gene.2012.12.103
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
The epigenetic regulation of microRNAs is one of several mechanisms underlying carcinogenesis. We found that microRNA-195 (miR-195) and microRNA-378 (miR-378) were significantly down-regulated in gastric cancer tissues and gastric cancer cell lines. The expression of miR-195 and miR-378 in gastric cancer cells was significantly restored by 5-aza-dC, a demethylation reagent. The low expression of miR-195 and miR-378 was closely related to the presence of promoter CpG island methylation. Treatment with miR-195/miR-378 mimics strikingly suppressed the growth of gastric cancer cells whereas promoted the growth of normal gastric epithelial cells. In contrast, administration of miR-195/miR-378 inhibitors significantly prevented the growth of normal gastric epithelial cells. Expression of cyclin-dependent kinase 6 and vascular endothelial growth factor was down-regulated by exogenous miR-195 and miR-378, respectively. In conclusion, miR-195 and miR-378 are abnormally expressed and epigenetically regulated in gastric cancer cell lines and tissues via the suppression of CDK6 and VEGF signaling, suggesting that miR-195 and miR-378 have tumor suppressor properties in gastric cancer. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码：351 / 359
页数：9
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