m<sup>6</sup>A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK

The N6-methyladenosine (m<sup>6</sup>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...

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Autores principales:	Guohui Li, Liang Deng, Nan Huang, Zhongqi Cui, Qi Wu, Ji Ma, Qiuhui Pan, Fenyong Sun
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	WTAP HCC autophagy LKB1 AMPK Genetics QH426-470
Acceso en línea:	https://doaj.org/article/025bb92f8f504f13a146f7016e08e295
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spelling	oai:doaj.org-article:025bb92f8f504f13a146f7016e08e2952021-11-25T17:41:29Zm<sup>6</sup>A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK10.3390/genes121117472073-4425https://doaj.org/article/025bb92f8f504f13a146f7016e08e2952021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1747https://doaj.org/toc/2073-4425The N6-methyladenosine (m<sup>6</sup>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.Guohui LiLiang DengNan HuangZhongqi CuiQi WuJi MaQiuhui PanFenyong SunMDPI AGarticleWTAPHCCautophagyLKB1AMPKGeneticsQH426-470ENGenes, Vol 12, Iss 1747, p 1747 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	WTAP HCC autophagy LKB1 AMPK Genetics QH426-470
spellingShingle	WTAP HCC autophagy LKB1 AMPK Genetics QH426-470 Guohui Li Liang Deng Nan Huang Zhongqi Cui Qi Wu Ji Ma Qiuhui Pan Fenyong Sun m<sup>6</sup>A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
description	The N6-methyladenosine (m<sup>6</sup>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.
format	article
author	Guohui Li Liang Deng Nan Huang Zhongqi Cui Qi Wu Ji Ma Qiuhui Pan Fenyong Sun
author_facet	Guohui Li Liang Deng Nan Huang Zhongqi Cui Qi Wu Ji Ma Qiuhui Pan Fenyong Sun
author_sort	Guohui Li
title	m<sup>6</sup>A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_short	m<sup>6</sup>A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_full	m<sup>6</sup>A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_fullStr	m<sup>6</sup>A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_full_unstemmed	m<sup>6</sup>A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK
title_sort	m<sup>6</sup>a mrna methylation regulates lkb1 to promote autophagy of hepatoblastoma cells through upregulated phosphorylation of ampk
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/025bb92f8f504f13a146f7016e08e295
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m<sup>6</sup>A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK

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