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.
基金：
National Natural Science Foundation of China [81572855, 81572427, 81874189, 82103597]; Graduates' Innovation Fund, Huazhong University of Science and Technology [5003540055]
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, Wuhan 430030, Peoples R China[2]Hubei Key Lab Hepatopancreatobiliary Dis, Wuhan 430030, Peoples R China
通讯作者：
通讯机构：[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, Wuhan 430030, Peoples R China[2]Hubei Key Lab Hepatopancreatobiliary Dis, Wuhan 430030, Peoples R China[3]Minist Educ, Key Lab Organ Transplantat, Wuhan 430030, Peoples R China[4]Minist Hlth, Wuhan 430030, Peoples R China
推荐引用方式(GB/T 7714)：
Zhang Hongwei,Liu Yachong,Wang Wei,et al.ALKBH5-mediated m6A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis[J].CELL DEATH & DISEASE.2022,13(11):doi:10.1038/s41419-022-05386-4.
APA：
Zhang, Hongwei,Liu, Yachong,Wang, Wei,Liu, Furong,Wang, Weijian...&Chen, Xiaoping.(2022).ALKBH5-mediated m6A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis.CELL DEATH & DISEASE,13,(11)
MLA：
Zhang, Hongwei,et al."ALKBH5-mediated m6A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis".CELL DEATH & DISEASE 13..11(2022)
生物学