MicroRNA-503 inhibits the G1/S transition by downregulating cyclin D3 and E2F3 in hepatocellular carcinoma

Journal of Translational Medicine

Lin Zhou²  Shusen Zheng²  Jun Cheng²  Haijun Guo¹  Kangjie Chen²  Songming Ding¹  Xiaobo Yu¹  Chunyang Xing¹  Haiyang Xie¹  Fei Chen³  Liming Chen²  Wu zhang²  Fenqiang Xiao¹ 

[1] Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, P.R. China;Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China;Institution of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China

关键词: G1/S transition;    Overall survival;    E2F3;    Cyclin D3;    microRNA-503;    Hepatocellular carcinoma;   

Others  :  826851
DOI  :  10.1186/1479-5876-11-195

 received in 2013-05-13, accepted in 2013-08-21,  发布年份 2013

【 摘 要 】

Background

Increasing evidence indicates that deregulation of microRNAs (miRNAs) is involved in tumorigenesis. Downregulation of microRNA-503 has been observed in various types of diseases, including cancer. However, the biological function of miR-503 in hepatocellular carcinoma (HCC) is still largely unknown. In this study we aimed to elucidate the prognostic implications of miR-503 in HCC and its pathophysiologic role.

Methods

Quantitative reverse transcriptase polymerase chain reaction was used to evaluate miR-503 expression in HCC tissues and cell lines. Western blotting was performed to evaluate the expression of the miR-503 target genes. In vivo and in vitro assays were performed to evaluate the function of miR-503 in HCC. Luciferase reporter assay was employed to validate the miR-503 target genes.

Results

miR-503 was frequently downregulated in HCC cell lines and tissues. Low expression levels of miR-503 were associated with enhanced malignant potential such as portal vein tumor thrombi, histologic grade, TNM stage, AFP level and poor prognosis. Multivariate analysis indicated that miR-503 downregulation was significantly associated with worse overall survival of HCC patients. Functional studies showed miR-503 suppressed the proliferation of HCC cells by induction of G1 phase arrest through Rb-E2F signaling pathways, and thus may function as a tumor suppressor. Further investigation characterized two cell cycle-related molecules, cyclin D3 and E2F3, as the direct miR-503 targets.

Conclusion

Our data highlight an important role for miR-503 in cell cycle regulation and in the molecular etiology of HCC, and implicate the potential application of miR-503 in prognosis prediction and miRNA-based HCC therapy.

【 授权许可】

   
2013 Xiao et al.; licensee BioMed Central Ltd.

【 图 表 】

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