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

Xiao, Fenqiang, zhang, Wu, Chen, Liming, Chen, Fei, Xie, Haiyang, Xing, Chunyang, Yu, Xiaobo, Ding, Songming, Chen, Kangjie, Guo, Haijun, Cheng, Jun, Zheng, Shusen, Zhou, Lin·2013·Journal of Translational Medicine
DOI 10.1186/1479-5876-11-195PMC PMC3765277
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Abstract

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.

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Metadata

Authors
Xiao, F., zhang, W., Chen, L., Chen, F., Xie, H., Xing, C., Yu, X., Ding, S., Chen, K., Guo, H., Cheng, J., Zheng, S., & Zhou, L.
Venue
Journal of Translational Medicine
Publisher
Springer Science and Business Media LLC
Published
2013-08-22
Volume
11
Issue
1
ISSN
1479-5876
DOI
10.1186/1479-5876-11-195
PMC
PMC3765277
Cited by
71
References
2
Language
en

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