CircRNA_MYLK promotes malignant progression of ovarian cancer through regulating microRNA-652

Y. Zhao, Y. Hu, Q. Shen, Q. Chen, X.-J. Zhu, S.-S. Jiang, Q. Zhang

Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China. 617674846@163.com

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• Oncology

OBJECTIVE: The purpose of this study was to investigate circRNA_MYLK level in ovarian cancer (OC), and to further investigate whether it could promote the malignant progression of OC via regulating microRNA-652.

PATIENTS AND METHODS: quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine circRNA_MYLK level in 46 tumor tissue specimens and paracancerous normal ones collected from OC patients, and the interplay between circRNA_MYLK expression and clinical indicators of OC and patient prognosis was analyzed. Meanwhile, qPCR was also used to further verify circRNA_MYLK level in OC cell lines. In addition, circRNA_MYLK knockdown model was constructed using lentivirus in OC cell lines including A2780 and CAOV3, and the impacts of circRNA_MYLK on the biological functions of OC cells was evaluated using Cell Counting Kit-8 (CCK-8) and cloning experiments. Finally, Luciferase reporting assay and recovery experiment were performed to investigate the regulatory interplay between circRNA_MYLK and microRNA-652.

RESULTS: qPCR results indicated that circRNA_MYLK level in OC patients was remarkably higher than that in adjacent ones, and the difference was statistically significant. Compared with patients with low expression of circRNA_MYLK, patients with high expression of circRNA_MYLK had a higher pathological staging and a lower overall survival rate. Compared with the control group (sh-NC), the OC cell proliferation ability was remarkably attenuated in the circRNA_MYLK knockdown group (sh-circRNA). In addition, qPCR verification revealed that the expression levels of microRNA-652 and circRNA_MYLK were negatively correlated in OC tissues. At the same time, bioinformatics analysis and Luciferase reporter gene assay results confirmed that circRNA_MYLK can be targeted by microRNA-652. Finally, it was found that simultaneous knockdown of circRNA_MYKK and microRNA-652 could reverse the enhanced OC cell proliferative capacity induced by downregulation of circRNA_MYLK alone.

CONCLUSIONS: CircRNA_MYLK may promote the malignant progression of OC via regulating microRNA-652, and its expression was remarkably associated with pathological staging and poor prognosis in patients with OC.

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