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FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer most frequently detected at an advanced stage that limits treatment options to systemic chemotherapy, which has provided only marginal positive clinical outcomes. Currently, the first-line chemotherapeutic agent for PDAC is gemcit...

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Autores principales: Lu, Jin, Yang, Yongsheng, Liu, Xiangliang, Chen, Xiao, Song, Wei, Liu, Zefeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620239/
https://www.ncbi.nlm.nih.gov/pubmed/37914721
http://dx.doi.org/10.1038/s41419-023-06244-7
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author Lu, Jin
Yang, Yongsheng
Liu, Xiangliang
Chen, Xiao
Song, Wei
Liu, Zefeng
author_facet Lu, Jin
Yang, Yongsheng
Liu, Xiangliang
Chen, Xiao
Song, Wei
Liu, Zefeng
author_sort Lu, Jin
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer most frequently detected at an advanced stage that limits treatment options to systemic chemotherapy, which has provided only marginal positive clinical outcomes. Currently, the first-line chemotherapeutic agent for PDAC is gemcitabine (GEM). However, the chemotherapy resistance to GEM is often overlooked in the clinical treatment of PDAC due to the lack of effective biological markers. Therefore, it is crucial to find new prognostic markers and therapeutic targets for patients with PDAC. In this study, we identified a novel regulatory mechanism in the development of resistance to GEM in PDAC. Here, we report that LINC01134 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that LINC01134 promotes PDAC resistance to GEM through facilitating stem cell features and modulating the cell cycle. Mechanistically, LINC01134 interactes with tumor suppressor miR-497-5p in PDAC cells. Increased LINC01134 downregulates miR-140-3p to promotes the oncogenic WNT5A expression. Moreover, m(6)A demethylase FTO participated in the upregulation of LINC01134 by maintaining LINC01134 mRNA stability through YTHDF2. Taken together, the present study suggested FTO-mediated LINC01134 stabilization to promote chemotherapy resistance to GEM through miR-140-3p/WNT5A/WNT pathway in PDAC. Our study identified new prognostic markers and new therapeutic targets for patients with PDAC. [Image: see text]
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spelling pubmed-106202392023-11-03 FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC Lu, Jin Yang, Yongsheng Liu, Xiangliang Chen, Xiao Song, Wei Liu, Zefeng Cell Death Dis Article Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer most frequently detected at an advanced stage that limits treatment options to systemic chemotherapy, which has provided only marginal positive clinical outcomes. Currently, the first-line chemotherapeutic agent for PDAC is gemcitabine (GEM). However, the chemotherapy resistance to GEM is often overlooked in the clinical treatment of PDAC due to the lack of effective biological markers. Therefore, it is crucial to find new prognostic markers and therapeutic targets for patients with PDAC. In this study, we identified a novel regulatory mechanism in the development of resistance to GEM in PDAC. Here, we report that LINC01134 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that LINC01134 promotes PDAC resistance to GEM through facilitating stem cell features and modulating the cell cycle. Mechanistically, LINC01134 interactes with tumor suppressor miR-497-5p in PDAC cells. Increased LINC01134 downregulates miR-140-3p to promotes the oncogenic WNT5A expression. Moreover, m(6)A demethylase FTO participated in the upregulation of LINC01134 by maintaining LINC01134 mRNA stability through YTHDF2. Taken together, the present study suggested FTO-mediated LINC01134 stabilization to promote chemotherapy resistance to GEM through miR-140-3p/WNT5A/WNT pathway in PDAC. Our study identified new prognostic markers and new therapeutic targets for patients with PDAC. [Image: see text] Nature Publishing Group UK 2023-11-01 /pmc/articles/PMC10620239/ /pubmed/37914721 http://dx.doi.org/10.1038/s41419-023-06244-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lu, Jin
Yang, Yongsheng
Liu, Xiangliang
Chen, Xiao
Song, Wei
Liu, Zefeng
FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC
title FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC
title_full FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC
title_fullStr FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC
title_full_unstemmed FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC
title_short FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC
title_sort fto-mediated linc01134 stabilization to promote chemoresistance through mir-140-3p/wnt5a/wnt pathway in pdac
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620239/
https://www.ncbi.nlm.nih.gov/pubmed/37914721
http://dx.doi.org/10.1038/s41419-023-06244-7
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