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

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...

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Autores principales: Liu, Yuwan, Shen, Zhangjin, Wei, Xinyi, Gu, Lingkai, Zheng, Mengxia, Zhang, Yanan, Cheng, Xiaodong, Fu, Yunfeng, Lu, Weiguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413200/
https://www.ncbi.nlm.nih.gov/pubmed/37499410
http://dx.doi.org/10.1016/j.tranon.2023.101746
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author Liu, Yuwan
Shen, Zhangjin
Wei, Xinyi
Gu, Lingkai
Zheng, Mengxia
Zhang, Yanan
Cheng, Xiaodong
Fu, Yunfeng
Lu, Weiguo
author_facet Liu, Yuwan
Shen, Zhangjin
Wei, Xinyi
Gu, Lingkai
Zheng, Mengxia
Zhang, Yanan
Cheng, Xiaodong
Fu, Yunfeng
Lu, Weiguo
author_sort Liu, Yuwan
collection PubMed
description 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.
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spelling pubmed-104132002023-08-11 CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis Liu, Yuwan Shen, Zhangjin Wei, Xinyi Gu, Lingkai Zheng, Mengxia Zhang, Yanan Cheng, Xiaodong Fu, Yunfeng Lu, Weiguo Transl Oncol Original Research 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. Neoplasia Press 2023-07-25 /pmc/articles/PMC10413200/ /pubmed/37499410 http://dx.doi.org/10.1016/j.tranon.2023.101746 Text en © 2023 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Liu, Yuwan
Shen, Zhangjin
Wei, Xinyi
Gu, Lingkai
Zheng, Mengxia
Zhang, Yanan
Cheng, Xiaodong
Fu, Yunfeng
Lu, Weiguo
CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis
title CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis
title_full CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis
title_fullStr CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis
title_full_unstemmed CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis
title_short CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis
title_sort circslc39a8 attenuates paclitaxel resistance in ovarian cancer by regulating the mir‑185‑5p/bmf axis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413200/
https://www.ncbi.nlm.nih.gov/pubmed/37499410
http://dx.doi.org/10.1016/j.tranon.2023.101746
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