期刊
GENE
卷 518, 期 2, 页码 351-359出版社
ELSEVIER
DOI: 10.1016/j.gene.2012.12.103
关键词
MicroRNA; Gastric cancer; Tumor suppressor; Cell cycle; Epigenetic
资金
- Excellent Dissertation Fund of Ningbo University [PY201014, PY20110020]
- College Students' Science Technology Innovation Program of Zhejiang Province [200959]
- Scientific Innovation Team Project of Ningbo [2011882014]
- Ningbo Natural Science Foundation [2010A610044, 2012A610207]
- Zhejiang Provincial Research Project [201003112, 2012C23127]
- National Natural Science Foundation of China [81171660]
- Medical Science-Technology Project of Ningbo [2010806]
- KC Wong Magna Fund of Ningbo University
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.
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