ALKBH5-mediated m6A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis

被引：40
作者：
Zhang, Hongwei [1 ,2 ]
Liu, Yachong [1 ,2 ]
Wang, Wei [1 ,2 ]
Liu, Furong [1 ,2 ]
Wang, Weijian [1 ,2 ]
Su, Chen [1 ,2 ]
Zhu, He [1 ,2 ]
Liao, Zhibin [1 ,2 ]
Zhang, Bixiang [1 ,2 ,3 ,4 ]
Chen, Xiaoping [1 ,2 ,3 ,4 ]
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
来源：
CELL DEATH & DISEASE | 2022年 / 13卷 / 11期
基金：
中国国家自然科学基金;
关键词：
RNA; LANDSCAPE; PROTEIN; PATHWAY;
D O I：
10.1038/s41419-022-05386-4
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
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页数：12
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