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ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma

Obesity is often regarded as a factor that promotes tumorigenesis, but the role of obesity in promoting hepatocellular carcinoma (HCC) is still controversial. We compared the trend change of 14 obesity-related genes in the formation and development of HCC in normal, adjacent, and HCC tissues. Mendel...

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Autores principales: Zhang, Yiyin, Cheng, Jiaxi, Zhong, Cheng, Xia, Qiming, Li, Yirun, Chen, Peng, Fan, Xiaoxiao, Mao, Qijiang, Lin, Hui, Hong, Defei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252523/
https://www.ncbi.nlm.nih.gov/pubmed/35795061
http://dx.doi.org/10.3389/fonc.2022.899969
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author Zhang, Yiyin
Cheng, Jiaxi
Zhong, Cheng
Xia, Qiming
Li, Yirun
Chen, Peng
Fan, Xiaoxiao
Mao, Qijiang
Lin, Hui
Hong, Defei
author_facet Zhang, Yiyin
Cheng, Jiaxi
Zhong, Cheng
Xia, Qiming
Li, Yirun
Chen, Peng
Fan, Xiaoxiao
Mao, Qijiang
Lin, Hui
Hong, Defei
author_sort Zhang, Yiyin
collection PubMed
description Obesity is often regarded as a factor that promotes tumorigenesis, but the role of obesity in promoting hepatocellular carcinoma (HCC) is still controversial. We compared the trend change of 14 obesity-related genes in the formation and development of HCC in normal, adjacent, and HCC tissues. Mendelian randomization (MR) analysis was used to verify the relationship between obesity and HCC occurrence. Metabolism of cobalamin-associated A (MMAA) was discovered as an obesity- and metabolism-differential gene, and its function in HCC was tested in vitro and in vivo. Finally, we explored how obese female patients with an originally high expression of female estrogen receptor (ESR1) directly upregulated MMAA to interfere with the progression of HCC. Fourteen obesity-related genes were downregulated in adjacent and tumoral tissues compared with normal liver tissues, which indicated that obesity may be inversely related to the occurrence of HCC and was consistent with the results of MR analysis. We also discovered that MMAA is a metabolic gene closely related to the occurrence and development of HCC by mining the TCGA database, and it functioned an anti-tumor-promoting role in HCC by damaging the mitochondrial function and preserving the redox balance. We further verified that obese females with a high expression of ESR1 can regulate MMAA to protect HCC from progression. This study elucidates that obesity might be a protective factor for female HCC patients, as they originally highly expressed ESR1, which could upregulate MMAA to suppress tumor growth and participate in metabolic reprogramming.
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spelling pubmed-92525232022-07-05 ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma Zhang, Yiyin Cheng, Jiaxi Zhong, Cheng Xia, Qiming Li, Yirun Chen, Peng Fan, Xiaoxiao Mao, Qijiang Lin, Hui Hong, Defei Front Oncol Oncology Obesity is often regarded as a factor that promotes tumorigenesis, but the role of obesity in promoting hepatocellular carcinoma (HCC) is still controversial. We compared the trend change of 14 obesity-related genes in the formation and development of HCC in normal, adjacent, and HCC tissues. Mendelian randomization (MR) analysis was used to verify the relationship between obesity and HCC occurrence. Metabolism of cobalamin-associated A (MMAA) was discovered as an obesity- and metabolism-differential gene, and its function in HCC was tested in vitro and in vivo. Finally, we explored how obese female patients with an originally high expression of female estrogen receptor (ESR1) directly upregulated MMAA to interfere with the progression of HCC. Fourteen obesity-related genes were downregulated in adjacent and tumoral tissues compared with normal liver tissues, which indicated that obesity may be inversely related to the occurrence of HCC and was consistent with the results of MR analysis. We also discovered that MMAA is a metabolic gene closely related to the occurrence and development of HCC by mining the TCGA database, and it functioned an anti-tumor-promoting role in HCC by damaging the mitochondrial function and preserving the redox balance. We further verified that obese females with a high expression of ESR1 can regulate MMAA to protect HCC from progression. This study elucidates that obesity might be a protective factor for female HCC patients, as they originally highly expressed ESR1, which could upregulate MMAA to suppress tumor growth and participate in metabolic reprogramming. Frontiers Media S.A. 2022-06-20 /pmc/articles/PMC9252523/ /pubmed/35795061 http://dx.doi.org/10.3389/fonc.2022.899969 Text en Copyright © 2022 Zhang, Cheng, Zhong, Xia, Li, Chen, Fan, Mao, Lin and Hong 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
Zhang, Yiyin
Cheng, Jiaxi
Zhong, Cheng
Xia, Qiming
Li, Yirun
Chen, Peng
Fan, Xiaoxiao
Mao, Qijiang
Lin, Hui
Hong, Defei
ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma
title ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma
title_full ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma
title_fullStr ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma
title_full_unstemmed ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma
title_short ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma
title_sort esr1 regulates the obesity- and metabolism-differential gene mmaa to inhibit the occurrence and development of hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252523/
https://www.ncbi.nlm.nih.gov/pubmed/35795061
http://dx.doi.org/10.3389/fonc.2022.899969
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