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Ovarian cancer (OC) is the malignant tumor with the highest mortality among gynecological cancers. Chemotherapy resistance is a major obstacle to OC therapy. Circular RNAs (circRNAs) play crucial roles in cancer development and chemoresistance. However, the role and potential mechanism of has-circ-001567 (circ-VPS13C) in chemoresistance of OC remain unknown. Material and methods The levels of circ-VPS13C, miR-106b-5p and 14-3-3 zeta (YWHAZ) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell Counting Kit-8 (CCK-8) assay was used to assess cell viability and calculate the half inhibition concentration (IC50) of cisplatin (DDP). The levels of autophagy-related markers were measured by western blot assay. Cell apoptosis and migration were evaluated by flow cytometry and transwell assay, respectively. The binding relationship between miR-106b-5p and circ-VPS13C or YWHAZ was confirmed by dualluciferase reporter assay. Xenograft assay was performed to explore the role of circ-VPS13C in vivo. Results Circ-VPS13C and YWHAZ were up-regulated, while miR-106b-5p was down-regulated in DDPresistant OC tissues and cells. Knockdown of circ-VPS13C enhanced DDP sensitivity by repressing autophagy in DDP-resistant cells. Circ-VPS13C increased DDP resistance via sponging miR-106b-5p. Moreover, miR-106b-5p directly targeted YWHAZ. Up-regulation of YWHAZ alleviated the decrease in DDP resistance caused by circ-VPS13C depletion. In addition, circ-VPS13C silencing decreased DDP resistance in vivo. Conclusions Circ-VPS13C knockdown enhanced DDP sensitivity of OC through modulation of autophagy via the miR-106b-5p/YWHAZ axis, providing a new biomarker for improving the efficacy of OC chemotherapy. Powered by TCPDF (www.tcpdf.org) Pr ep ri t Circ-VPS13C enhances cisplatin resistance in ovarian cancer via modulating miR1 106b-5p/YWHAZ axis 2 3 Hairong Yao, Dantong Liu, Fangyuan Gao, Qian Li, Shikai Liu 4 Department of Gynecology, Cangzhou Central Hospital, Cangzhou City, Hebei 5 Province, China 6 Corresponding author: Shikai Liu, Department of Gynecology, Cangzhou Central 7 Hospital, No. 16 Xinhua West Road, Yunhe District, Cangzhou 061000, Hebei, China. 8 Tel: +86-182-33739102, E-mail: ojsfg6@163.com 9

Circ-VPS13C enhances cisplatin resistance in ovarian cancer via modulating miR-106b-5p/YWHAZ axis