CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis

Yuwan Liu; Zhangjin Shen; Xinyi Wei; Lingkai Gu; Mengxia Zheng; Yanan Zhang; Xiaodong Cheng; Yunfeng Fu; Weiguo Lu

doi:10.1016/j.tranon.2023.101746

CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis

Transl Oncol. 2023 Oct:36:101746. doi: 10.1016/j.tranon.2023.101746. Epub 2023 Jul 25.

Authors

Yuwan Liu¹, Zhangjin Shen¹, Xinyi Wei¹, Lingkai Gu¹, Mengxia Zheng¹, Yanan Zhang², Xiaodong Cheng³, Yunfeng Fu⁴, Weiguo Lu⁵

Affiliations

¹ Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.
² Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.
³ Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, China.
⁴ Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China. Electronic address: 5100008@zju.edu.cn.
⁵ Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Zhejiang Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Hangzhou, Zhejiang 310006, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: lbwg@zju.edu.cn.

Abstract

Chemoresistance to paclitaxel (PTX) is one of the main reasons for treatment failure and poor prognosis in patients with advanced ovarian cancer. Therefore, it is imperative to explore the mechanisms related to chemotherapy resistance in ovarian cancer to find potential therapeutic targets. Circular RNAs (circRNAs) play important roles in cancer development and progression. However, their biological functions and clinical significance in ovarian cancer have not been fully elucidated. Therefore, in this study, we aimed to investigate the function and underlying mechanism of hsa_circ_0002782 (circSLC39A8), identified by circRNA sequencing, in regulating PTX resistance. The effects of circSLC39A8 on PTX resistance was assessed by cell viability, colony formation, flow cytometry assays and an in vivo subcutaneous xenografted tumor mouse model. RNA immunoprecipitation and dual-luciferase reporter assays were performed to verify the interaction between circSLC39A8 and the miR-185-5p/BMF signal axis. We found that circSLC39A8 was downregulated in PTX-resistant ovarian cancer cells and tissues, and its low expression was associated with poor prognosis. Biologically, circSLC39A8 knockdown promoted PTX resistance in vitro and in vivo, while circSLC39A8 overexpression showed the opposite effect. Mechanistically, circSLC39A8, acting as an endogenous sponge for miR-185-5p, could relieve the inhibition of miR-185-5p on the expression of its downstream target, BMF; thus enhancing the sensitivity of ovarian cancer to PTX. Our findings demonstrate that circSLC39A8 can promote PTX sensitivity by regulating the miR-185-5p/BMF axis. This may be a valuable prognostic biomarker and a promising therapeutic target for patients with ovarian cancer.

Keywords: BMF; Ovarian cancer; Paclitaxel resistance; circSLC39A8; miR-185–5p.