MiR-99a suppressed cell proliferation and invasion by directly targeting HOXA1 through regulation of the AKT/mTOR signaling pathway and EMT in ovarian cancer

L. Zhang, X.-L. Liu, Z. Yuan, J. Cui, H. Zhang

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China. nhylldh5376363@163.com

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• Oncology

OBJECTIVE: Ovarian cancer (OC) is the third frequently tumor worldwide. MicroRNA-99a (miR-99a), acting as a tumor suppressor, has been reported to be downregulated in multiple tumors. We aimed at exploring the significant roles of miR-99a in ovarian cancer.

PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blotting were applied to calculate the mRNA and protein levels of miR-99a and its target genes. Kaplan-Meier method was conducted to evaluate the overall survival of ovarian cancer patients. CCK8 and transwell assays were performed to measure the proliferative and invasive abilities.

RESULTS: miR-99a, acting as a prognosis predictor, was downregulated in ovarian cancer tissues and cell lines. miR-99a mediated the expression of homeobox A1 (HOXA1) through directly targeting to the 3’-untranslated region (3’-UTR) of its mRNA in ovarian cancer cell lines. miR-99a inhibited the proliferation of ovarian cancer by AKT/mTOR pathway in vitro and in vivo, and it suppressed the invasion-mediated epithelial-mesenchymal transition (EMT) through direct targeting to the 3’-UTR of HOXA1 mRNA.

CONCLUSIONS: miR-99a suppressed the proliferation through AKT/mTOR signaling pathway and the invasion-mediated EMT in ovarian cancer. The newly identified miR-99a/HOXA1/AKT/mTOR axis provides novel insight into the pathogenesis of ovarian cancer.

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