Aberrant NSUN2-mediated m(5)C modification of H19 lncRNA is associated with poor differentiation of hepatocellular carcinoma.
Aberrant NSUN2-mediated m(5)C modification of H19 lncRNA is associated with poor differentiation of hepatocellular carcinoma.
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NSUN2 介导的 H19 lncRNA 异常 m 5 C 修饰与肝细胞癌分化不良相关
DOI：
10.1038/s41388-020-01475-w
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发表时间：
2020-11
期刊：
影响因子：
8
通讯作者：
Cui H
中科院分区：
文献类型：
--
作者：
Sun Z;Xue S;Zhang M;Xu H;Hu X;Chen S;Liu Y;Guo M;Cui H
RNA甲基化是一种重要的表观遗传修饰。目前对RNA甲基化的研究主要集中在mRNA的m6 A修饰上，而对m5 C修饰的研究很少。NSUN 2是一种RNA甲基转移酶，负责多种RNA的m5 C修饰。在本研究中，我们通过CRISPR/Cas9技术敲除HepG 2细胞中的NSUN 2基因，并进行高通量RNA-BisSeq。一种重要的肿瘤相关lncRNA H19被鉴定为NSUN 2靶向。研究表明，H19 lncRNA的表达异常升高，在多种类型的肿瘤中具有致癌作用。我们的结果表明，H19 lncRNA的m5 C修饰可以增加其稳定性。有趣的是，m5 C修饰的H19 lncRNA可以与G3 BP 1特异性结合，G3 BP 1是一种众所周知的癌蛋白，进一步导致MYC积累。这可能是lncRNA H19发挥其致癌作用的一种新机制。此外，肝癌组织中m5 C甲基化水平和H19 lncRNA表达水平均显著高于癌旁组织，这与肝癌的低分化密切相关。总之，我们发现H19 RNA是NSUN 2修饰剂的特异性靶标。m5 C修饰的H19 lncRNA可能通过募集G3 BP 1癌蛋白而促进肿瘤的发生和发展。我们的研究结果可能为肝癌的诊断和治疗提供一个潜在的靶点和生物标志物。
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.
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影响因子：
4.6
作者：
Bian Z;Jin L;Zhang J;Yin Y;Quan C;Hu Y;Feng Y;Liu H;Fei B;Mao Y;Zhou L;Qi X;Huang S;Hua D;Xing C;Huang Z
通讯作者：
Huang Z
影响因子：
3.1
作者：
Okamoto, Mayumi;Hirata, Sumi;Tatsuka, Masaaki
通讯作者：
Tatsuka, Masaaki
Rho GTPases控制细胞运动过程中的极性，突出和粘附。
影响因子：
7.8
作者：
Nobes, C D;Hall, A
通讯作者：
Hall, A
影响因子：
8.8
作者：
Hussain S;Sajini AA;Blanco S;Dietmann S;Lombard P;Sugimoto Y;Paramor M;Gleeson JG;Odom DT;Ule J;Frye M
通讯作者：
Frye M
影响因子：
11.2
作者：
Barsyte-Lovejoy, Dalia;Lau, Suzanne K.;Penn, Linda Z.
通讯作者：
Penn, Linda Z.