Aberrant NSUN2-mediated MC Modification of H19 LncRNA is Associated with Poor Differentiation of Hepatocellular Carcinoma

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2020 Sep 26

PMID 32978516

Citations 136

Authors

Zhen Sun

Songlei Xue

Meiying Zhang

Hui Xu

Xuming Hu

Shihao Chen

YangYang Liu

Mingzhou Guo

Hengmi Cui

Affiliations

Soon will be listed here.

Abstract

RNA methylation is an important epigenetic modification. Recent studies on RNA methylation mainly focus on the mA modification of mRNA, but very little is known about the mC modification. NSUN2 is an RNA methyltransferase responsible for the mC modification of multiple RNAs. In this study, we knocked down the NSUN2 gene in HepG2 cells by CRISPR/Cas9 technology and performed high-throughput RNA-BisSeq. An important tumor-related lncRNA H19 was identified to be targeted by NSUN2. Studies have shown that the expression of H19 lncRNA is abnormally elevated and has a carcinogenic effect in many types of tumors. Our results demonstrated that mC modification of H19 lncRNA can increase its stability. Interestingly, mC-modified H19 lncRNA can be specifically bound by G3BP1, a well-known oncoprotein which further leads to MYC accumulation. This may be a novel mechanism by which lncRNA H19 exerts its oncogenic effect. Besides, both the mC methylation level and the expression level of H19 lncRNA in hepatocellular carcinoma tissues were significantly higher than those in adjacent non-cancer tissues, which were closely associated with poor differentiation of hepatocellular carcinoma (HCC). In conclusion, we found that H19 RNA is a specific target for the NSUN2 modifier. The mC-modified H19 lncRNA may promote the occurrence and development of tumors by recruiting the G3BP1 oncoprotein. Our findings may provide a potential target and biomarker for the diagnosis and treatment of HCC.

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