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Tumour-suppressive microRNA-424-5p directly targets CCNE1 as potential prognostic markers in epithelial ovarian cancer

ORCID Icon, , , ORCID Icon, & ORCID Icon
Pages 309-318 | Received 29 Sep 2017, Accepted 17 Nov 2017, Published online: 02 Jan 2018
 

ABSTRACT

An accumulated evidence supports that MicroRNAs (miRNAs) have shown a prominent role in pathological processes and different tumor onset. However, to date, the potential functional roles and molecular mechanisms by how microRNA-424-5p(miR-424-5p) affects cancer cell proliferation are greatly unclear, especially in epithelial ovarian cancer(EOC).In this study, we demonstrated that miR-424-5p was significantly down-regulated in EOC tissues and cell lines. The level of miR-424-5p was negatively correlated with tumor size, TNM stage, pathological grade, lymphatic metastasis of EOC. Restoring miR-424-5p expression in EOC cells dramatically suppressed cell proliferation and caused an accumulation of cells in G1 phase, and thus contributed to better prognosis of EOC patients. Mechanistically, miR-424-5p inhibits CCNE1 expression through targeting CCNE1 3′UTR, and subsequent arrest cell cycle in G1/G0 phase by inhibiting E2F1-pRb pathway. This study revealed functional and mechanistic links between miR-424-5p and CCNE1 in the progression of EOC and provide an important insight into that miR-424-5p may serve as a therapeutic target in EOC.

Disclosure of potential conflicts of interest

The authors declare that they have no conflicts of interest.

Acknowledgments

We thank for Professor Jinbo Feng and Zhenping Liu from Gene Research Cente for technical assistance and Professor Beihua Kong's supplyment of cell lines. We appreciate Dr. Ming Yang's help for collecting tissues (Qilu Hospital, Shandong University).

Additional information

Funding

This study was supported by National Natural Science Foundation of China (NO. 81372809) and National Clinical Research Center for Gynecological Oncology (NO. 2015BAI13B05).

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