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LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis

Chronic inflammation promotes the tumorigenesis and cell stemness maintenance of colorectal cancer (CRC). However, the bridge role of long noncoding RNA (lncRNA) in linking chronic inflammation to CRC development and progression needs better understanding. Here, we elucidated a novel function of lnc...

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Autores principales: Ye, Deji, Liu, Hanshao, Zhao, Guojun, Chen, Aijun, Jiang, Yuhang, Hu, Yiming, Liu, Dandan, Xie, Ningxia, Liang, Weifei, Chen, Xi, Zhang, Haohao, Li, Cuifeng, Wang, Jingyao, Sun, Donglin, Chen, Weifeng, Tan, Dan, Wang, Qi, Wang, Hongru, Yu, Dianping, Wu, Baojin, Wang, Mingliang, Cui, Shuzhong, Liu, Sanhong, Zhang, Xiaoren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970971/
https://www.ncbi.nlm.nih.gov/pubmed/36849492
http://dx.doi.org/10.1038/s41419-023-05700-8
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author Ye, Deji
Liu, Hanshao
Zhao, Guojun
Chen, Aijun
Jiang, Yuhang
Hu, Yiming
Liu, Dandan
Xie, Ningxia
Liang, Weifei
Chen, Xi
Zhang, Haohao
Li, Cuifeng
Wang, Jingyao
Sun, Donglin
Chen, Weifeng
Tan, Dan
Wang, Qi
Wang, Hongru
Yu, Dianping
Wu, Baojin
Wang, Mingliang
Cui, Shuzhong
Liu, Sanhong
Zhang, Xiaoren
author_facet Ye, Deji
Liu, Hanshao
Zhao, Guojun
Chen, Aijun
Jiang, Yuhang
Hu, Yiming
Liu, Dandan
Xie, Ningxia
Liang, Weifei
Chen, Xi
Zhang, Haohao
Li, Cuifeng
Wang, Jingyao
Sun, Donglin
Chen, Weifeng
Tan, Dan
Wang, Qi
Wang, Hongru
Yu, Dianping
Wu, Baojin
Wang, Mingliang
Cui, Shuzhong
Liu, Sanhong
Zhang, Xiaoren
author_sort Ye, Deji
collection PubMed
description Chronic inflammation promotes the tumorigenesis and cell stemness maintenance of colorectal cancer (CRC). However, the bridge role of long noncoding RNA (lncRNA) in linking chronic inflammation to CRC development and progression needs better understanding. Here, we elucidated a novel function of lncRNA GMDS-AS1 in persistently activated signal transducer and transcription activator 3 (STAT3) and Wnt signaling and CRC tumorigenesis. Interleukin-6 (IL-6) and Wnt3a induced lncRNA GMDS-AS1 expression, which was highly expressed in the CRC tissues and plasma of CRC patients. GMDS-AS1 knockdown impaired the survival, proliferation and stem cell-like phenotype acquisition of CRC cells in vitro and in vivo. We performed RNA sequencing (RNA-seq) and mass spectrometry (MS) to probe target proteins and identify their contributions to the downstream signaling pathways of GMDS-AS1. In CRC cells, GMDS-AS1 physically interacted with the RNA-stabilizing protein HuR, thereby protecting the HuR protein from polyubiquitination- and proteasome-dependent degradation. HuR stabilized STAT3 mRNA and upregulated the levels of basal and phosphorylated STAT3 protein, persistently activating STAT3 signaling. Our research revealed that the lncRNA GMDS-AS1 and its direct target HuR constitutively activate STAT3/Wnt signaling and promote CRC tumorigenesis, the GMDS-AS1-HuR-STAT3/Wnt axis is a therapeutic, diagnostic and prognostic target in CRC.
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spelling pubmed-99709712023-03-01 LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis Ye, Deji Liu, Hanshao Zhao, Guojun Chen, Aijun Jiang, Yuhang Hu, Yiming Liu, Dandan Xie, Ningxia Liang, Weifei Chen, Xi Zhang, Haohao Li, Cuifeng Wang, Jingyao Sun, Donglin Chen, Weifeng Tan, Dan Wang, Qi Wang, Hongru Yu, Dianping Wu, Baojin Wang, Mingliang Cui, Shuzhong Liu, Sanhong Zhang, Xiaoren Cell Death Dis Article Chronic inflammation promotes the tumorigenesis and cell stemness maintenance of colorectal cancer (CRC). However, the bridge role of long noncoding RNA (lncRNA) in linking chronic inflammation to CRC development and progression needs better understanding. Here, we elucidated a novel function of lncRNA GMDS-AS1 in persistently activated signal transducer and transcription activator 3 (STAT3) and Wnt signaling and CRC tumorigenesis. Interleukin-6 (IL-6) and Wnt3a induced lncRNA GMDS-AS1 expression, which was highly expressed in the CRC tissues and plasma of CRC patients. GMDS-AS1 knockdown impaired the survival, proliferation and stem cell-like phenotype acquisition of CRC cells in vitro and in vivo. We performed RNA sequencing (RNA-seq) and mass spectrometry (MS) to probe target proteins and identify their contributions to the downstream signaling pathways of GMDS-AS1. In CRC cells, GMDS-AS1 physically interacted with the RNA-stabilizing protein HuR, thereby protecting the HuR protein from polyubiquitination- and proteasome-dependent degradation. HuR stabilized STAT3 mRNA and upregulated the levels of basal and phosphorylated STAT3 protein, persistently activating STAT3 signaling. Our research revealed that the lncRNA GMDS-AS1 and its direct target HuR constitutively activate STAT3/Wnt signaling and promote CRC tumorigenesis, the GMDS-AS1-HuR-STAT3/Wnt axis is a therapeutic, diagnostic and prognostic target in CRC. Nature Publishing Group UK 2023-02-27 /pmc/articles/PMC9970971/ /pubmed/36849492 http://dx.doi.org/10.1038/s41419-023-05700-8 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
Ye, Deji
Liu, Hanshao
Zhao, Guojun
Chen, Aijun
Jiang, Yuhang
Hu, Yiming
Liu, Dandan
Xie, Ningxia
Liang, Weifei
Chen, Xi
Zhang, Haohao
Li, Cuifeng
Wang, Jingyao
Sun, Donglin
Chen, Weifeng
Tan, Dan
Wang, Qi
Wang, Hongru
Yu, Dianping
Wu, Baojin
Wang, Mingliang
Cui, Shuzhong
Liu, Sanhong
Zhang, Xiaoren
LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis
title LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis
title_full LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis
title_fullStr LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis
title_full_unstemmed LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis
title_short LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis
title_sort lncgmds-as1 promotes the tumorigenesis of colorectal cancer through hur-stat3/wnt axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970971/
https://www.ncbi.nlm.nih.gov/pubmed/36849492
http://dx.doi.org/10.1038/s41419-023-05700-8
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