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

被引：230

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 [遗传学];

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

页码：351 / 359

页数：9

共 47 条

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