期刊
TUMOR BIOLOGY
卷 37, 期 5, 页码 5821-5828出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-015-4427-6
关键词
Hepatocellular carcinoma; miR-15a-5p; BDNF; Cancer proliferation; Cell cycle
类别
资金
- Science and Technology Planning Project of Guangdong Province [2013B021800284]
- National Natural Science Foundation of China [81272312, 81300421]
We examined the expression pattern and functional roles of microRNA 15a-5p (miR-15a-5p) in human hepatocellular carcinoma (HCC). Possible miR-15a-5p aberrant expression in HCC cell lines or clinical HCC specimens was examined by quantitative real-time PCR (qRT-PCR). In HCC HepG2 and SNU-182 cells, miR-15a-5p was ectopically overexpressed by lentiviral transduction. Its effect on HCC proliferation, cancer division, and in vivo tumor growth were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, and tumorigenicity assay, respectively. The targeting of miR-15a-5p on its downstream gene, brain-derived neurotrophic factor (BDNF), was examined by dual-luciferase assay, qRT-PCR, and Western blot, respectively. BDNF was then overexpressed in HepG2 and SNU-182 cells to evaluate its selective effect on miR-15a-5p in HCC modulation. MiR-15a-5p is aberrantly downregulated in in vitro HCC cell lines and in vivo HCC clinical specimens. Ectopic overexpression of miR-15a-5p suppressed cancer proliferation, induced cell cycle arrest in HepG2 or SNU-182 cells in vitro, and inhibited HCC tumor growth in vivo. MiR-15a-5p selectively and negatively regulated BDNF at both gene and protein levels in HCC cells. Forced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-15a-5p on HCC proliferation and cell division in vitro. Our study demonstrated that miR-15a-5p is a tumor suppressor in HCC and its regulation is through BDNF in HCC.
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