ALKBH5-mediated m6A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis
Hongwei Zhang, Yachong Liu, Wei Wang, Furong Liu, Weijian Wang, Su Chen, He Zhu, Zhibin Liao, Bixiang Zhang, Xiaoping Chen
Abstract
Abstract 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.