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MicroRNA-10a inhibits hepatocellular carcinoma cell proliferation through targeting E2F3
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Abstract:
Objective: To investigate the role of microRNA-10a (miR-10a) in hepatocellular carcinoma (HCC) growth. Methods: Paired HCC and adjacent non-tumor tissue specimens were surgically collected from 144 patients who were diagnosed with primary HCC in Guangxi Medical University-Affiliated Tumor Hospital between October 2001 and July 2005. HCC QGY-7701, Huh7, and PCL/PRF/5 cells were transfected with miR-10a mimics or scramble control miRNA. The abundance of miR-10a in both tissue specimens and transfected cells was quantified by real-time PCR and E2F3 protein in transfected cells was assessed by Western blotting. Proliferation of the transfectants was assessed by a colorimetric cell counting assay. Cell cycle progression and apoptosis of the transfectants were assessed by FACS. Results: The abundance of miR-10a mRNA was significantly lower in HCC tissue specimens than in normal tissue specimens (-9.89±168 vs -784±1.97, P =0.0001). HCC cells transfected with miR-10a mimics had miR-10a abundance 16 times higher than both wild-type HCC cells and HCC cells transfected with the control miRNA with scrambled sequences. Overexpression of miR-10a resulted in significant increases in suppression of HCC cell proliferation ( P <0.05） and G 1 phase arrest. In contrast, overexpression of miR-10a had no influence on apoptosis of HCC cells. Bioinformatics suggested that transcription factor E2F3 might be a downstream target of miR-10a and the expression of E2F3 in HCC cells transfected with miR-10a was significantly lower than in wild-type HCC cells and HCC cells transfected with the control miRNA (050±0.12 vs 0.79±0.21, P <0.05). Conclusion: MiR-10a may suppress HCC cell proliferation through G 1 phase arrest in an E2F3-dependent mechanism.
Keywords:
hepatocellular carcinoma ; microRNA-10a（miR-10a) ; transcription factor ; E2F3 ; proliferation ; G 1/S phase arrest
Project Supported:
Project supported by the National High Technology Research and Development Program of China （863 Program) (No. 2012AA020901)
