MiRNA-96 accelerates the malignant progression of ovarian cancer via targeting FOXO3a

N. Yang, Q. Zhang, X.-J. Bi

Department of Gynecology, The Centre Hospital Weinan, Weinan, China. Bixuejie688@sina.com

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• Oncology

OBJECTIVE: To clarify the potential function of miRNA-96 in accelerating the malignant progression of ovarian cancer (OC) and its underlying mechanism.

PATIENTS AND METHODS: The expression patterns of miRNA-96 in 36 matched OC tissues and adjacent normal tissues were determined by qRT-PCR. We analyzed the correlation between the miRNA-96 level and the clinical parameters of OC patients. Subsequently, the cellular levels of miRNA-96 in OC cell lines were determined as well. To construct miRNA-96 inhibitor and NC, the regulatory effects of miRNA-96 on the proliferative and migratory abilities in OC cells were examined. The target gene of miRNA-96 was verified by Dual-Luciferase Reporter Gene Assay. Finally, the rescue experiments were conducted to clarify the regulatory role of miRNA-96/FOXO3a axis in the malignant progression of OC.

RESULTS: MiRNA-96 was upregulated in OC tissues relative to adjacent normal ones. Compared with OC patients presenting high-level of miRNA-96, those with low-level miRNA-96 suffered more advanced tumor staging and a worse overall survival. The transfection of miRNA-96 inhibitor markedly attenuated proliferative and migratory abilities in SKOV3 and CAOV3 cells. In addition, FOXO3a was identified to be the target gene of miRNA-96, which was negatively regulated by miRNA-96. FOXO3a exerted a lower abundance in OC tissues relative to adjacent normal ones. Finally, the rescue experiments revealed that FOXO3a knockdown could abolish the inhibitory role of miRNA-96 knockdown in the proliferative, migratory, and invasive abilities in OC cells.

CONCLUSIONS: The knockdown of miRNA-96 attenuated the proliferative and migratory abilities in OC cells by targeting FOXO3a. We believed that miRNA-96 accelerates the malignant progression of OC, which could be utilized as a therapeutic target in clinical application.

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