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YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer

Activation of PI3K/AKT signalling by PTEN loss significantly enhances chemoresistance in bladder cancer. This study aims to evaluate PTEN regulation and identify targets that could be used to relieve chemoresistance. Expression of YTHDC1, γ‐H2AX and PTEN were detected by IHC assay. Cell Counting Kit...

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Autores principales: Su, Yinjie, Wang, Bo, Huang, Jian, Huang, Ming, Lin, Tianxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334275/
https://www.ncbi.nlm.nih.gov/pubmed/37070134
http://dx.doi.org/10.1111/cpr.13404
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author Su, Yinjie
Wang, Bo
Huang, Jian
Huang, Ming
Lin, Tianxin
author_facet Su, Yinjie
Wang, Bo
Huang, Jian
Huang, Ming
Lin, Tianxin
author_sort Su, Yinjie
collection PubMed
description Activation of PI3K/AKT signalling by PTEN loss significantly enhances chemoresistance in bladder cancer. This study aims to evaluate PTEN regulation and identify targets that could be used to relieve chemoresistance. Expression of YTHDC1, γ‐H2AX and PTEN were detected by IHC assay. Cell Counting Kit‐8 assay, colony formation assay and tumour xenograft experiment evaluated cisplatin response. Flow cytometry and comet assay estimated cell apoptosis, cell cycle distribution and DNA repair capability. Quantitative real‐time polymerase chain reaction, Western blot and RIP assay assessed binding properties between PTEN mRNA and YTHDC1. Silencing YTHDC1 in bladder cancer cells reduced PTEN expression and activated PI3K/AKT signalling by destabilizing PTEN mRNA in an m(6)A‐dependent manner. Low YTHDC1 expression indicated poor cisplatin sensitivity in bladder cancer patients. Reducing YTHDC1 expression promoted drug resistance to cisplatin, while over‐expressing YTHDC1 promoted cisplatin sensitivity. Reducing YTHDC1 expression activated DNA damage response, which includes quicker cell cycle recovery, apoptosis evasion and an enhanced DNA repair capability, whereas these effects were attenuated when MK2206, a PI3K/AKT inhibitor was applied. We provide novel evidence that PTEN/PI3K/AKT signalling pathway could be regulated by YTHDC1 in an m(6)A‐dependent manner and highlight a critical role of YTHDC1 in cisplatin resistance of bladder cancer.
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spelling pubmed-103342752023-07-12 YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer Su, Yinjie Wang, Bo Huang, Jian Huang, Ming Lin, Tianxin Cell Prolif Original Articles Activation of PI3K/AKT signalling by PTEN loss significantly enhances chemoresistance in bladder cancer. This study aims to evaluate PTEN regulation and identify targets that could be used to relieve chemoresistance. Expression of YTHDC1, γ‐H2AX and PTEN were detected by IHC assay. Cell Counting Kit‐8 assay, colony formation assay and tumour xenograft experiment evaluated cisplatin response. Flow cytometry and comet assay estimated cell apoptosis, cell cycle distribution and DNA repair capability. Quantitative real‐time polymerase chain reaction, Western blot and RIP assay assessed binding properties between PTEN mRNA and YTHDC1. Silencing YTHDC1 in bladder cancer cells reduced PTEN expression and activated PI3K/AKT signalling by destabilizing PTEN mRNA in an m(6)A‐dependent manner. Low YTHDC1 expression indicated poor cisplatin sensitivity in bladder cancer patients. Reducing YTHDC1 expression promoted drug resistance to cisplatin, while over‐expressing YTHDC1 promoted cisplatin sensitivity. Reducing YTHDC1 expression activated DNA damage response, which includes quicker cell cycle recovery, apoptosis evasion and an enhanced DNA repair capability, whereas these effects were attenuated when MK2206, a PI3K/AKT inhibitor was applied. We provide novel evidence that PTEN/PI3K/AKT signalling pathway could be regulated by YTHDC1 in an m(6)A‐dependent manner and highlight a critical role of YTHDC1 in cisplatin resistance of bladder cancer. John Wiley and Sons Inc. 2023-04-17 /pmc/articles/PMC10334275/ /pubmed/37070134 http://dx.doi.org/10.1111/cpr.13404 Text en © 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Su, Yinjie
Wang, Bo
Huang, Jian
Huang, Ming
Lin, Tianxin
YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer
title YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer
title_full YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer
title_fullStr YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer
title_full_unstemmed YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer
title_short YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer
title_sort ythdc1 positively regulates pten expression and plays a critical role in cisplatin resistance of bladder cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334275/
https://www.ncbi.nlm.nih.gov/pubmed/37070134
http://dx.doi.org/10.1111/cpr.13404
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