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N(6)-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1

Abnormal RNA m6A methylation is known to lead to the occurrence and progression of multiple cancers including gastric cancer (GC). However, the integrative effects of all m6A methylation regulators on GC prognosis are unclear. Our research aimed to globally analyze the prognosis values of all 33 m6A...

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Autores principales: Wang, Duo, Qu, Xiujuan, Lu, Wenqing, Wang, Yizhe, Jin, Yue, Hou, Kezuo, Yang, Bowen, Li, Ce, Qi, Jianfei, Xiao, Jiawen, Che, Xiaofang, Liu, Yunpeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282183/
https://www.ncbi.nlm.nih.gov/pubmed/34277426
http://dx.doi.org/10.3389/fonc.2021.681280
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author Wang, Duo
Qu, Xiujuan
Lu, Wenqing
Wang, Yizhe
Jin, Yue
Hou, Kezuo
Yang, Bowen
Li, Ce
Qi, Jianfei
Xiao, Jiawen
Che, Xiaofang
Liu, Yunpeng
author_facet Wang, Duo
Qu, Xiujuan
Lu, Wenqing
Wang, Yizhe
Jin, Yue
Hou, Kezuo
Yang, Bowen
Li, Ce
Qi, Jianfei
Xiao, Jiawen
Che, Xiaofang
Liu, Yunpeng
author_sort Wang, Duo
collection PubMed
description Abnormal RNA m6A methylation is known to lead to the occurrence and progression of multiple cancers including gastric cancer (GC). However, the integrative effects of all m6A methylation regulators on GC prognosis are unclear. Our research aimed to globally analyze the prognosis values of all 33 m6A RNA methylation regulators in GC by univariate and multivariate Cox regression analyses. Among all 33 m6A RNA methylation regulators, fat mass and obesity-associated protein (FTO), an m6A demethylase, was identified as a key prognostic risk factor on overall survival (OS) of GC patients. It was found that FTO could promote GC cell migration and invasion abilities, and we predicted that ITGB1 was a demethylated target of FTO. Knockdown (KD) of FTO significantly down-regulated ITGB1 expression at both mRNA and protein levels and augmented ITGB1 mRNA m6A modification level. Moreover, overexpression (OE) of ITGB1 could partially reverse FTO-KD-inhibited migration and invasion of GC cells. Our study found that FTO was an independent risk factor for overall survival (OS) of GC patients and FTO could promote GC metastasis by upregulating the expression of Integrin β1(ITGB1) via decreasing its m6A level. These results indicated that FTO can be a potent GC biomarker for prognosis prediction as well as a potential target in GC treatment.
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spelling pubmed-82821832021-07-16 N(6)-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1 Wang, Duo Qu, Xiujuan Lu, Wenqing Wang, Yizhe Jin, Yue Hou, Kezuo Yang, Bowen Li, Ce Qi, Jianfei Xiao, Jiawen Che, Xiaofang Liu, Yunpeng Front Oncol Oncology Abnormal RNA m6A methylation is known to lead to the occurrence and progression of multiple cancers including gastric cancer (GC). However, the integrative effects of all m6A methylation regulators on GC prognosis are unclear. Our research aimed to globally analyze the prognosis values of all 33 m6A RNA methylation regulators in GC by univariate and multivariate Cox regression analyses. Among all 33 m6A RNA methylation regulators, fat mass and obesity-associated protein (FTO), an m6A demethylase, was identified as a key prognostic risk factor on overall survival (OS) of GC patients. It was found that FTO could promote GC cell migration and invasion abilities, and we predicted that ITGB1 was a demethylated target of FTO. Knockdown (KD) of FTO significantly down-regulated ITGB1 expression at both mRNA and protein levels and augmented ITGB1 mRNA m6A modification level. Moreover, overexpression (OE) of ITGB1 could partially reverse FTO-KD-inhibited migration and invasion of GC cells. Our study found that FTO was an independent risk factor for overall survival (OS) of GC patients and FTO could promote GC metastasis by upregulating the expression of Integrin β1(ITGB1) via decreasing its m6A level. These results indicated that FTO can be a potent GC biomarker for prognosis prediction as well as a potential target in GC treatment. Frontiers Media S.A. 2021-07-01 /pmc/articles/PMC8282183/ /pubmed/34277426 http://dx.doi.org/10.3389/fonc.2021.681280 Text en Copyright © 2021 Wang, Qu, Lu, Wang, Jin, Hou, Yang, Li, Qi, Xiao, Che and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wang, Duo
Qu, Xiujuan
Lu, Wenqing
Wang, Yizhe
Jin, Yue
Hou, Kezuo
Yang, Bowen
Li, Ce
Qi, Jianfei
Xiao, Jiawen
Che, Xiaofang
Liu, Yunpeng
N(6)-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1
title N(6)-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1
title_full N(6)-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1
title_fullStr N(6)-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1
title_full_unstemmed N(6)-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1
title_short N(6)-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1
title_sort n(6)-methyladenosine rna demethylase fto promotes gastric cancer metastasis by down-regulating the m6a methylation of itgb1
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282183/
https://www.ncbi.nlm.nih.gov/pubmed/34277426
http://dx.doi.org/10.3389/fonc.2021.681280
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