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

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资源类型：
Pubmed体系：
作者：
Ye Deji[1,2] * ; Liu Hanshao[2] * ; Zhao Guojun[1] * ; Chen Aijun[3] ; Jiang Yuhang[1,2] ; Hu Yiming[1,2] ; Liu Dandan[1,2] ; Xie Ningxia[1,2] ; Liang Weifei[1] ; Chen Xi[2] ; Zhang Haohao[1,2] ; Li Cuifeng[1,2] ; Wang Jingyao[1] ; Sun Donglin[1] ; Chen Weifeng[1] ; Tan Dan[3] ; Wang Qi[1,2] ; Wang Hongru[4] ; Yu Dianping[4] ; Wu Baojin[5] ; Wang Mingliang[3] ; Cui Shuzhong[1] ; Liu Sanhong[4] ; Zhang Xiaoren[1,2] ;
机构： [1]The Sixth Affiliated Hospital, Affiliated Cancer Hospital/Institute and GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, Qingyuan People’s Hospital, StateKey Laboratory of Respiratory Disease, Qingyuan 511518 Guangdong, China [2]CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition andHealth, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China [3]General SurgeryDepartment, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China [4]Shanghai Frontiers Science Center of TCM Chemical Biology, Institute ofInterdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China [5]Shanghai Institute of Biochemistry and CellBiology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
出处：
DOI： 10.1038/s41419-023-05700-8

摘要：
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.© 2023. The Author(s).

基金：
National Program on Key Research (2021YFA0804703); the National Natural Science Foundation of China (82272633, 91949102 and 91742113); the Guangzhou Key Medical Discipline Construction Project Fund and the Open research funds from the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
第一作者：
第一作者机构： [1]The Sixth Affiliated Hospital, Affiliated Cancer Hospital/Institute and GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, Qingyuan People’s Hospital, StateKey Laboratory of Respiratory Disease, Qingyuan 511518 Guangdong, China [2]CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition andHealth, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
共同第一作者：
通讯作者：
通讯机构： [1]The Sixth Affiliated Hospital, Affiliated Cancer Hospital/Institute and GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, Qingyuan People’s Hospital, StateKey Laboratory of Respiratory Disease, Qingyuan 511518 Guangdong, China [2]CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition andHealth, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
推荐引用方式(GB/T 7714)：
Ye Deji,Liu Hanshao,Zhao Guojun,et al.LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis[J].Cell death & disease.2023,14(2):165.doi:10.1038/s41419-023-05700-8.
APA：
Ye Deji,Liu Hanshao,Zhao Guojun,Chen Aijun,Jiang Yuhang...&Zhang Xiaoren.(2023).LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis.Cell death & disease,14,(2)
MLA：
Ye Deji,et al."LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis".Cell death & disease 14..2(2023):165

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