ALKBH5-mediated m(6)A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis

As the most important RNA epigenetic regulation in eukaryotic cells, N6-metheyladenosine (m(6)A) modification has been demonstrated to play significant roles in cancer progression. However, this modification in long intergenic non-coding RNAs (lincRNAs) and the corresponding functions remain elusive...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Hongwei, Liu, Yachong, Wang, Wei, Liu, Furong, Wang, Weijian, Su, Chen, Zhu, He, Liao, Zhibin, Zhang, Bixiang, Chen, Xiaoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637195/
https://www.ncbi.nlm.nih.gov/pubmed/36335087
http://dx.doi.org/10.1038/s41419-022-05386-4
_version_ 1784825131418255360
author Zhang, Hongwei
Liu, Yachong
Wang, Wei
Liu, Furong
Wang, Weijian
Su, Chen
Zhu, He
Liao, Zhibin
Zhang, Bixiang
Chen, Xiaoping
author_facet Zhang, Hongwei
Liu, Yachong
Wang, Wei
Liu, Furong
Wang, Weijian
Su, Chen
Zhu, He
Liao, Zhibin
Zhang, Bixiang
Chen, Xiaoping
author_sort Zhang, Hongwei
collection PubMed
description As the most important RNA epigenetic regulation in eukaryotic cells, N6-metheyladenosine (m(6)A) modification has been demonstrated to play significant roles in cancer progression. However, this modification in long intergenic non-coding RNAs (lincRNAs) and the corresponding functions remain elusive. Here, we showed a lincRNA LINC02551 was downregulated by AlkB Homolog 5 (ALKBH5) overexpression in a m(6)A-dependent manner in hepatocellular carcinoma (HCC). Functionally, LINC02551 was required for the growth and metastasis of HCC. Mechanistically, LINC02551, a bona fide m(6)A target of ALKBH5, acted as a molecular adaptor that blocked the combination between DDX24 and a E3 ligase TRIM27 to decrease the ubiquitination and subsequent degradation of DDX24, ultimately facilitating HCC growth and metastasis. Thus, ALKBH5-mediated LINC02551 m(6)A methylation was required for HCC growth and metastasis.
format Online
Article
Text
id pubmed-9637195
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-96371952022-11-07 ALKBH5-mediated m(6)A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis Zhang, Hongwei Liu, Yachong Wang, Wei Liu, Furong Wang, Weijian Su, Chen Zhu, He Liao, Zhibin Zhang, Bixiang Chen, Xiaoping Cell Death Dis Article As the most important RNA epigenetic regulation in eukaryotic cells, N6-metheyladenosine (m(6)A) modification has been demonstrated to play significant roles in cancer progression. However, this modification in long intergenic non-coding RNAs (lincRNAs) and the corresponding functions remain elusive. Here, we showed a lincRNA LINC02551 was downregulated by AlkB Homolog 5 (ALKBH5) overexpression in a m(6)A-dependent manner in hepatocellular carcinoma (HCC). Functionally, LINC02551 was required for the growth and metastasis of HCC. Mechanistically, LINC02551, a bona fide m(6)A target of ALKBH5, acted as a molecular adaptor that blocked the combination between DDX24 and a E3 ligase TRIM27 to decrease the ubiquitination and subsequent degradation of DDX24, ultimately facilitating HCC growth and metastasis. Thus, ALKBH5-mediated LINC02551 m(6)A methylation was required for HCC growth and metastasis. Nature Publishing Group UK 2022-11-05 /pmc/articles/PMC9637195/ /pubmed/36335087 http://dx.doi.org/10.1038/s41419-022-05386-4 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
Zhang, Hongwei
Liu, Yachong
Wang, Wei
Liu, Furong
Wang, Weijian
Su, Chen
Zhu, He
Liao, Zhibin
Zhang, Bixiang
Chen, Xiaoping
ALKBH5-mediated m(6)A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis
title ALKBH5-mediated m(6)A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis
title_full ALKBH5-mediated m(6)A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis
title_fullStr ALKBH5-mediated m(6)A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis
title_full_unstemmed ALKBH5-mediated m(6)A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis
title_short ALKBH5-mediated m(6)A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis
title_sort alkbh5-mediated m(6)a modification of lincrna linc02551 enhances the stability of ddx24 to promote hepatocellular carcinoma growth and metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637195/
https://www.ncbi.nlm.nih.gov/pubmed/36335087
http://dx.doi.org/10.1038/s41419-022-05386-4
work_keys_str_mv AT zhanghongwei alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis
AT liuyachong alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis
AT wangwei alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis
AT liufurong alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis
AT wangweijian alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis
AT suchen alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis
AT zhuhe alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis
AT liaozhibin alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis
AT zhangbixiang alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis
AT chenxiaoping alkbh5mediatedm6amodificationoflincrnalinc02551enhancesthestabilityofddx24topromotehepatocellularcarcinomagrowthandmetastasis

Ejemplares similares