Silencing circ‑BIRC6 inhibits the proliferation, invasion, migration and epithelial‑mesenchymal transition of bladder cancer cells by targeting the miR‑495‑3p/XBP1 signaling axis

Zhou,Lei; Wang,Bingzhi; Zhang,Yichuan; Yao,Kun; Liu,Bin

doi:10.3892/mmr.2021.12451

Silencing circ‑BIRC6 inhibits the proliferation, invasion, migration and epithelial‑mesenchymal transition of bladder cancer cells by targeting the miR‑495‑3p/XBP1 signaling axis

Authors:
- Lei Zhou
- Bingzhi Wang
- Yichuan Zhang
- Kun Yao
- Bin Liu
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Affiliations: Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: September 20, 2021 https://doi.org/10.3892/mmr.2021.12451
Article Number: 811
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Circular RNAs (circRNAs) regulate gene expression by acting as a ‘sponge’ for microRNAs (miRs) and play crucial roles in tumorigenesis, including in bladder cancer (BC). circRNA‑baculoviral IAP repeat‑containing 6 (circ‑BIRC6) has been reported to participate in the pathogenesis of several cancer types. The present study aimed to elucidate the roles and potential mechanisms of circ‑BIRC6 in the progression of BC. circ‑BIRC6 expression levels in BC cell lines were determined using reverse transcription‑quantitative PCR. Following circ‑BIRC6 knockdown, cell proliferation, invasion and migration were detected using Cell Counting Kit‑8, colony formation, Transwell and wound healing assays, respectively. Western blotting was also conducted to evaluate the expression levels of X‑box binding protein 1 (XBP1) and epithelial‑mesenchymal transition (EMT)‑associated proteins. In addition, rescue experiments were performed using by transfecting a miR‑495‑3p inhibitor into T24 cells following circ‑BIRC6 knockdown. The interactions between circ‑BIRC6, miR‑495‑3p and XBP1 was verified using dual luciferase reporter assays. Moreover, T24 cells with circ‑BIRC6 knockdown and miR‑495‑3p inhibitor transfection were used for the tumor‑bearing experiment. Tumor growth was observed and Ki‑67 expression was determined using immunohistochemistry. The results demonstrated that circ‑BIRC6 expression was upregulated in BC cell lines. Moreover, circ‑BIRC6 knockdown notably attenuated the proliferation, invasion, migration and EMT of BC cells, which was blocked by the miR‑495‑3p inhibitor. It was also identified that circ‑BIRC6 sponged miR‑495‑3p to regulate XBP1 expression. In addition, results from the xenograft experiments indicated that the knockdown of circ‑BIRC6 and miR‑495‑3p expression significantly inhibited tumor growth. It was also found that the expression levels of XBP1, Ki‑67 and EMT‑associated proteins in tumor tissues of the co‑transfection group were markedly restored compared with the circ‑BIRC6 knockdown group. In conclusion, these findings demonstrated that circ‑BIRC6 knockdown suppressed BC tumorigenesis and progression via regulation of the miR‑495‑3p/XBP1 signaling axis, offering a promising therapeutic target for the treatment of BC.

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