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Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p

Bladder cancer (BC) is one of the most common malignant tumors of the urinary system, and cisplatin (CDDP) is a critical chemical drug for the treatment of BC. However, CDDP-resistance seriously limits the therapeutic efficacy of this drug for clinical utilization. Thus, identification of pivotal mo...

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Autores principales: Sun, Ming, Liu, Xuefeng, Zhao, Wenyan, Zhang, Bin, Deng, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943922/
https://www.ncbi.nlm.nih.gov/pubmed/35321689
http://dx.doi.org/10.1186/s12885-022-09419-1
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author Sun, Ming
Liu, Xuefeng
Zhao, Wenyan
Zhang, Bin
Deng, Peng
author_facet Sun, Ming
Liu, Xuefeng
Zhao, Wenyan
Zhang, Bin
Deng, Peng
author_sort Sun, Ming
collection PubMed
description Bladder cancer (BC) is one of the most common malignant tumors of the urinary system, and cisplatin (CDDP) is a critical chemical drug for the treatment of BC. However, CDDP-resistance seriously limits the therapeutic efficacy of this drug for clinical utilization. Thus, identification of pivotal molecule targets that regulate CDDP-resistance in BC become urgent and necessary. In this study, we firstly identified a novel BC-associated circular RNA circ_0058063 that participates in the regulation of CDDP-resistance in BC. Specifically, circ_0058063 was significantly overexpressed in CDDP-resistant tissue and cells, in contrast with the corresponding CDDP-sensitive counterparts. Further loss-of-function experiments validated that downregulation of circ_0058063 suppressed cell proliferation and tumor growth, whereas induced cell apoptosis in the CDDP-resistant BC cells in vitro and in vivo. In addition, we disclosed that circ_0058063 acts as a sponge for miR-335-5p to positively regulate B2M expression, and further rescuing experiments verified that the enhancing effects of sh-circ_0058063 on CDDP-sensitivity in the CDDP-resistant BC cells were abrogated by silencing miR-335-5p. Taken together, our results demonstrated that circ_0058063 contributed to CDDP resistance of bladder cancer cells via sponging miR-335-5p, and B2M might be the downstream effector gene. This study firstly evidenced that targeting circ_0058063 might be an effective strategy to improve CDDP-sensitivity in BC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09419-1.
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spelling pubmed-89439222022-03-25 Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p Sun, Ming Liu, Xuefeng Zhao, Wenyan Zhang, Bin Deng, Peng BMC Cancer Research Bladder cancer (BC) is one of the most common malignant tumors of the urinary system, and cisplatin (CDDP) is a critical chemical drug for the treatment of BC. However, CDDP-resistance seriously limits the therapeutic efficacy of this drug for clinical utilization. Thus, identification of pivotal molecule targets that regulate CDDP-resistance in BC become urgent and necessary. In this study, we firstly identified a novel BC-associated circular RNA circ_0058063 that participates in the regulation of CDDP-resistance in BC. Specifically, circ_0058063 was significantly overexpressed in CDDP-resistant tissue and cells, in contrast with the corresponding CDDP-sensitive counterparts. Further loss-of-function experiments validated that downregulation of circ_0058063 suppressed cell proliferation and tumor growth, whereas induced cell apoptosis in the CDDP-resistant BC cells in vitro and in vivo. In addition, we disclosed that circ_0058063 acts as a sponge for miR-335-5p to positively regulate B2M expression, and further rescuing experiments verified that the enhancing effects of sh-circ_0058063 on CDDP-sensitivity in the CDDP-resistant BC cells were abrogated by silencing miR-335-5p. Taken together, our results demonstrated that circ_0058063 contributed to CDDP resistance of bladder cancer cells via sponging miR-335-5p, and B2M might be the downstream effector gene. This study firstly evidenced that targeting circ_0058063 might be an effective strategy to improve CDDP-sensitivity in BC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09419-1. BioMed Central 2022-03-23 /pmc/articles/PMC8943922/ /pubmed/35321689 http://dx.doi.org/10.1186/s12885-022-09419-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sun, Ming
Liu, Xuefeng
Zhao, Wenyan
Zhang, Bin
Deng, Peng
Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p
title Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p
title_full Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p
title_fullStr Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p
title_full_unstemmed Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p
title_short Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p
title_sort circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating b2m through acting as rna sponges for mir-335-5p
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943922/
https://www.ncbi.nlm.nih.gov/pubmed/35321689
http://dx.doi.org/10.1186/s12885-022-09419-1
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