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m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer
Gastric cancer (GC) is a malignancy with poor prognosis. NDUFA4 is reported to correlate with the progression of GC. However, its underlying mechanism in GC is unknown. Our study was to reveal the pathogenic mechanism of NDUFA4 in GC. NDUFA4 expression was explored in single-cell and bulk RNA-seq da...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385701/ https://www.ncbi.nlm.nih.gov/pubmed/35977935 http://dx.doi.org/10.1038/s41419-022-05132-w |
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author | Xu, Weihong Lai, Yanan Pan, Yunqi Tan, Meiyu Ma, Yanyun Sheng, Huiming Wang, Jiucun |
author_facet | Xu, Weihong Lai, Yanan Pan, Yunqi Tan, Meiyu Ma, Yanyun Sheng, Huiming Wang, Jiucun |
author_sort | Xu, Weihong |
collection | PubMed |
description | Gastric cancer (GC) is a malignancy with poor prognosis. NDUFA4 is reported to correlate with the progression of GC. However, its underlying mechanism in GC is unknown. Our study was to reveal the pathogenic mechanism of NDUFA4 in GC. NDUFA4 expression was explored in single-cell and bulk RNA-seq data as well as GC tissue microarray. Mitochondrial respiration and glycolysis were estimated by oxygen consumption rate and extracellular acidification rate, respectively. The interaction between NDUFA4 and METTL3 was validated by RNA immunoprecipitation. Flow cytometry was used to estimate cell cycle, apoptosis and mitochondrial activities. NDUFA4 was highly expressed in GC and its high expression indicated a poor prognosis. The knockdown of NDUFA4 could reduce cell proliferation and inhibit tumor growth. Meanwhile, NDUFA4 could promote glycolytic and oxidative metabolism in GC cells, whereas the inhibition of glycolysis suppressed the proliferation and tumor growth of GC. Besides, NDUFA4 inhibited ROS level and promoted MMP level in GC cells, whereas the inhibition of mitochondrial fission could reverse NDUFA4-induced glycolytic and oxidative metabolism and tumor growth of GC. Additionally, METTL3 could increase the m6A level of NDUFA4 mRNA via the m6A reader IGF2BP1 to promote NDUFA4 expression in GC cells. Our study revealed that NDUFA4 was increased by m6A methylation and could promote GC development via enhancing cell glycolysis and mitochondrial fission. NDUFA4 was a potential target for GC treatment. |
format | Online Article Text |
id | pubmed-9385701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93857012022-08-19 m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer Xu, Weihong Lai, Yanan Pan, Yunqi Tan, Meiyu Ma, Yanyun Sheng, Huiming Wang, Jiucun Cell Death Dis Article Gastric cancer (GC) is a malignancy with poor prognosis. NDUFA4 is reported to correlate with the progression of GC. However, its underlying mechanism in GC is unknown. Our study was to reveal the pathogenic mechanism of NDUFA4 in GC. NDUFA4 expression was explored in single-cell and bulk RNA-seq data as well as GC tissue microarray. Mitochondrial respiration and glycolysis were estimated by oxygen consumption rate and extracellular acidification rate, respectively. The interaction between NDUFA4 and METTL3 was validated by RNA immunoprecipitation. Flow cytometry was used to estimate cell cycle, apoptosis and mitochondrial activities. NDUFA4 was highly expressed in GC and its high expression indicated a poor prognosis. The knockdown of NDUFA4 could reduce cell proliferation and inhibit tumor growth. Meanwhile, NDUFA4 could promote glycolytic and oxidative metabolism in GC cells, whereas the inhibition of glycolysis suppressed the proliferation and tumor growth of GC. Besides, NDUFA4 inhibited ROS level and promoted MMP level in GC cells, whereas the inhibition of mitochondrial fission could reverse NDUFA4-induced glycolytic and oxidative metabolism and tumor growth of GC. Additionally, METTL3 could increase the m6A level of NDUFA4 mRNA via the m6A reader IGF2BP1 to promote NDUFA4 expression in GC cells. Our study revealed that NDUFA4 was increased by m6A methylation and could promote GC development via enhancing cell glycolysis and mitochondrial fission. NDUFA4 was a potential target for GC treatment. Nature Publishing Group UK 2022-08-17 /pmc/articles/PMC9385701/ /pubmed/35977935 http://dx.doi.org/10.1038/s41419-022-05132-w Text en © The Author(s) 2022 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 Xu, Weihong Lai, Yanan Pan, Yunqi Tan, Meiyu Ma, Yanyun Sheng, Huiming Wang, Jiucun m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer |
title | m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer |
title_full | m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer |
title_fullStr | m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer |
title_full_unstemmed | m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer |
title_short | m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer |
title_sort | m6a rna methylation-mediated ndufa4 promotes cell proliferation and metabolism in gastric cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385701/ https://www.ncbi.nlm.nih.gov/pubmed/35977935 http://dx.doi.org/10.1038/s41419-022-05132-w |
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