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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...

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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:
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
Descripción
Sumario: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.