期刊
ONCOTARGET
卷 6, 期 10, 页码 7675-7685出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3048
关键词
1,25(OH)(2)D-3; miR-145; gastric cancer; E2F3; proliferation
资金
- National Natural Science Foundation of China [31100921, 81171398]
- Fundamental Research Funds for the Central Universities [08142006]
- Program for Changjiang Scholars and Innovative Research Team in University [PCSIRT: 1171]
VitaminD3 signaling is involved in inhibiting the development and progression of gastric cancer (GC), while the active vitamin D metabolite 1-alpha, 25-dihydroxyvitamin D3 (1,25(OH)(2)D-3)-mediated gene regulatory mechanisms in GC remain unclear. We found that miR-145 is induced by 1,25(OH)(2)D-3 in a dose-and vitamin D receptor (VDR)-dependent manner in GC cells. Inhibition of miR-145 reverses the antiproliferative effect of 1,25(OH)(2)D-3. Furthermore, miR-145 expression was lower in tumors compared with matched normal samples and correlated with increased the E2F3 transcription factor protein staining. Overexpression of miR-145 inhibited colony formation, cell viability and induced cell arrest in S-phase in GC cells by targeting E2F3 and CDK6. miR-145 inhibition consistently abrogates the 1,25(OH)(2)D-3-mediated suppression of E2F3, CDK6, CDK2 and CCNA2 genes. Altogether, our results indicate that miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 in GC cells and might hold promise for prognosis and therapeutic strategies for GC treatment.
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