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m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK

The N6-methyladenosine (m(6)A) RNA modification can regulate autophagy to modulate the growth and development of tumors, but the mechanism of m6A modification for the regulation of autophagy in hepatocellular carcinoma cells (HCC) remains unclear. In the study, the knockdown of the Wilms’ tumor 1-as...

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Autores principales: Li, Guohui, Deng, Liang, Huang, Nan, Cui, Zhongqi, Wu, Qi, Ma, Ji, Pan, Qiuhui, Sun, Fenyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621998/
https://www.ncbi.nlm.nih.gov/pubmed/34828353
http://dx.doi.org/10.3390/genes12111747
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author Li, Guohui
Deng, Liang
Huang, Nan
Cui, Zhongqi
Wu, Qi
Ma, Ji
Pan, Qiuhui
Sun, Fenyong
author_facet Li, Guohui
Deng, Liang
Huang, Nan
Cui, Zhongqi
Wu, Qi
Ma, Ji
Pan, Qiuhui
Sun, Fenyong
author_sort Li, Guohui
collection PubMed
description The N6-methyladenosine (m(6)A) RNA modification can regulate autophagy to modulate the growth and development of tumors, but the mechanism of m6A modification for the regulation of autophagy in hepatocellular carcinoma cells (HCC) remains unclear. In the study, the knockdown of the Wilms’ tumor 1-associating protein (WTAP) was made in HCC to study the correlation between m6A modification and autophagy. A fluorescent confocal microscopy analysis showed that the knockdown of WTAP could facilitate the autophagy of HCC. A Western blot analysis showed that the level of p-AMPK was decreased in WTAP-knockdown HCC cells. Additionally, LKB1, the upstream kinase of AMPK, was regulated by WTAP and it could mediate the phosphorylation of AMPK in an m6A-dependent manner. Further studies revealed that the knockdown of WTAP could reduce the level of LKB1 mRNA with m6A. This could result in the increased stability of LKB1 mRNA to promote its expression. The knockdown of WTAP could upregulate the level of autophagy and inhibit HCC proliferation. However, the overexpression of WTAP could resist autophagic cell death.
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spelling pubmed-86219982021-11-27 m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK Li, Guohui Deng, Liang Huang, Nan Cui, Zhongqi Wu, Qi Ma, Ji Pan, Qiuhui Sun, Fenyong Genes (Basel) Article The N6-methyladenosine (m(6)A) RNA modification can regulate autophagy to modulate the growth and development of tumors, but the mechanism of m6A modification for the regulation of autophagy in hepatocellular carcinoma cells (HCC) remains unclear. In the study, the knockdown of the Wilms’ tumor 1-associating protein (WTAP) was made in HCC to study the correlation between m6A modification and autophagy. A fluorescent confocal microscopy analysis showed that the knockdown of WTAP could facilitate the autophagy of HCC. A Western blot analysis showed that the level of p-AMPK was decreased in WTAP-knockdown HCC cells. Additionally, LKB1, the upstream kinase of AMPK, was regulated by WTAP and it could mediate the phosphorylation of AMPK in an m6A-dependent manner. Further studies revealed that the knockdown of WTAP could reduce the level of LKB1 mRNA with m6A. This could result in the increased stability of LKB1 mRNA to promote its expression. The knockdown of WTAP could upregulate the level of autophagy and inhibit HCC proliferation. However, the overexpression of WTAP could resist autophagic cell death. MDPI 2021-10-30 /pmc/articles/PMC8621998/ /pubmed/34828353 http://dx.doi.org/10.3390/genes12111747 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Guohui
Deng, Liang
Huang, Nan
Cui, Zhongqi
Wu, Qi
Ma, Ji
Pan, Qiuhui
Sun, Fenyong
m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_full m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_fullStr m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_full_unstemmed m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_short m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_sort m(6)a mrna methylation regulates lkb1 to promote autophagy of hepatoblastoma cells through upregulated phosphorylation of ampk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621998/
https://www.ncbi.nlm.nih.gov/pubmed/34828353
http://dx.doi.org/10.3390/genes12111747
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