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EGR1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer

OBJECTIVES: Long non‐coding RNAs (lncRNAs) are key mediators in various malignancies. Linc01503 was previously elucidated to promote gastric cancer (GC) cell invasion. However, the upstream mechanism of linc01503 and its involvement in GC cell cycle, apoptosis and tumorigenesis still remain unclear....

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Detalles Bibliográficos
Autores principales: Ma, Zhonghua, Gao, Xiangyu, Shuai, You, Wu, Xiaolong, Yan, Yan, Xing, Xiaofang, Ji, Jiafu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791171/
https://www.ncbi.nlm.nih.gov/pubmed/33145887
http://dx.doi.org/10.1111/cpr.12922
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author Ma, Zhonghua
Gao, Xiangyu
Shuai, You
Wu, Xiaolong
Yan, Yan
Xing, Xiaofang
Ji, Jiafu
author_facet Ma, Zhonghua
Gao, Xiangyu
Shuai, You
Wu, Xiaolong
Yan, Yan
Xing, Xiaofang
Ji, Jiafu
author_sort Ma, Zhonghua
collection PubMed
description OBJECTIVES: Long non‐coding RNAs (lncRNAs) are key mediators in various malignancies. Linc01503 was previously elucidated to promote gastric cancer (GC) cell invasion. However, the upstream mechanism of linc01503 and its involvement in GC cell cycle, apoptosis and tumorigenesis still remain unclear. MATERIALS AND METHODS: Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction (qRT‐PCR) assays were implicated to detect linc01503 level in GC. The role of linc01503 was detected by in vitro functional assays and in vivo xenograft tumour models. The association between linc01503 and its upstream effector was identified by chromatin immunoprecipitation (ChIP) assays. The mechanistic model of linc01503 was clarified using subcellular separation, fluorescence in situ hybridization, RNA‐sequencing, RNA immunoprecipitation (RIP) and ChIP assays. RESULTS: Linc01503 was remarkably elevated in GC and tightly linked with the overall survival of patients with GC. The key transcription factor early growth response protein 1 (EGR1) critically activated the transcription of linc01503. Functionally, linc01503 knockdown resulted in the activation of apoptosis and G1/G0 phase arrest in GC. Mechanistically, linc01503 interacted with histone modification enzyme enhancer of zeste 2 (EZH2) and lysine (K)‐specific demethylase 1A (LSD1), thereby mediating the transcriptional silencing of dual‐specificity phosphatase 5 (DUSP5) and cyclin‐dependent kinase inhibitor 1A (CDKN1A) in GC. CONCLUSIONS: EGR1‐activated linc01503 could epigenetically silence DUSP5/CDKN1A expression to mediate cell cycle progression and tumorigenesis, implicating it as a prospective target for GC therapeutics.
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spelling pubmed-77911712021-01-11 EGR1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer Ma, Zhonghua Gao, Xiangyu Shuai, You Wu, Xiaolong Yan, Yan Xing, Xiaofang Ji, Jiafu Cell Prolif Original Articles OBJECTIVES: Long non‐coding RNAs (lncRNAs) are key mediators in various malignancies. Linc01503 was previously elucidated to promote gastric cancer (GC) cell invasion. However, the upstream mechanism of linc01503 and its involvement in GC cell cycle, apoptosis and tumorigenesis still remain unclear. MATERIALS AND METHODS: Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction (qRT‐PCR) assays were implicated to detect linc01503 level in GC. The role of linc01503 was detected by in vitro functional assays and in vivo xenograft tumour models. The association between linc01503 and its upstream effector was identified by chromatin immunoprecipitation (ChIP) assays. The mechanistic model of linc01503 was clarified using subcellular separation, fluorescence in situ hybridization, RNA‐sequencing, RNA immunoprecipitation (RIP) and ChIP assays. RESULTS: Linc01503 was remarkably elevated in GC and tightly linked with the overall survival of patients with GC. The key transcription factor early growth response protein 1 (EGR1) critically activated the transcription of linc01503. Functionally, linc01503 knockdown resulted in the activation of apoptosis and G1/G0 phase arrest in GC. Mechanistically, linc01503 interacted with histone modification enzyme enhancer of zeste 2 (EZH2) and lysine (K)‐specific demethylase 1A (LSD1), thereby mediating the transcriptional silencing of dual‐specificity phosphatase 5 (DUSP5) and cyclin‐dependent kinase inhibitor 1A (CDKN1A) in GC. CONCLUSIONS: EGR1‐activated linc01503 could epigenetically silence DUSP5/CDKN1A expression to mediate cell cycle progression and tumorigenesis, implicating it as a prospective target for GC therapeutics. John Wiley and Sons Inc. 2020-11-03 /pmc/articles/PMC7791171/ /pubmed/33145887 http://dx.doi.org/10.1111/cpr.12922 Text en © 2020 The Authors. Cell Proliferation published by John Wiley & Sons Ltd This is an open access article under the terms of the http://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
Ma, Zhonghua
Gao, Xiangyu
Shuai, You
Wu, Xiaolong
Yan, Yan
Xing, Xiaofang
Ji, Jiafu
EGR1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer
title EGR1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer
title_full EGR1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer
title_fullStr EGR1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer
title_full_unstemmed EGR1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer
title_short EGR1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer
title_sort egr1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791171/
https://www.ncbi.nlm.nih.gov/pubmed/33145887
http://dx.doi.org/10.1111/cpr.12922
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