Aberrant NSUN2-mediated m
| Autor: | Zhen, Sun, Songlei, Xue, Meiying, Zhang, Hui, Xu, Xuming, Hu, Shihao, Chen, Yangyang, Liu, Mingzhou, Guo, Hengmi, Cui |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Carcinoma Hepatocellular Methylation Article Epigenesis Genetic Mice Animals Humans RNA-Seq Poly-ADP-Ribose Binding Proteins Cancer genetics Liver Neoplasms DNA Helicases Cell Differentiation Hep G2 Cells Methyltransferases Middle Aged Xenograft Model Antitumor Assays female genital diseases and pregnancy complications Gene Expression Regulation Neoplastic RNA Recognition Motif Proteins Liver Gene Knockdown Techniques embryonic structures 5-Methylcytosine Female RNA Long Noncoding Epigenetics RNA Helicases |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 |
| Popis: | RNA methylation is an important epigenetic modification. Recent studies on RNA methylation mainly focus on the m6A modification of mRNA, but very little is known about the m5C modification. NSUN2 is an RNA methyltransferase responsible for the m5C 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 m5C modification of H19 lncRNA can increase its stability. Interestingly, m5C-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 m5C 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 m5C-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. |
| Databáze: | OpenAIRE |
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