title: MicroRNA-195 and microRNA-378 mediate tumor growth suppression by epigenetical regulation in gastric cancer.
abstract: 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.
authors: Department of Biochemistry and Molecular Biology, and Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China.
authors: Hongxia
authors: H
authors: Deng
authors: Yanan
authors: Y
authors: Guo
authors: Haojun
authors: H
authors: Song
authors: Bingxiu
authors: B
authors: Xiao
authors: Weiliang
authors: W
authors: Sun
authors: Zhong
authors: Z
authors: Liu
authors: Xiuchong
authors: X
authors: Yu
authors: Tian
authors: T
authors: Xia
authors: Long
authors: L
authors: Cui
authors: Junming
authors: J
authors: Guo
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018899:CpG Islands / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000096:biosynthesis; D019175:DNA Methylation; D000077209:Decitabine; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C552722:MIRN195 microRNA, human; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; D000077209:Decitabine; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D001374:Azacitidine