RBM15 promotes hepatocellular carcinoma progression by regulating N6-methyladenosine modification of YES1 mRNA in an IGF2BP1-dependent manner.
RBM15 promotes hepatocellular carcinoma progression by regulating N6-methyladenosine modification of YES1 mRNA in an IGF2BP1-dependent manner.
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DOI：
10.1038/s41420-021-00703-w
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发表时间：
2021-10-27
影响因子：
7
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Cai X;Chen Y;Man D;Yang B;Feng X;Zhang D;Chen J;Wu J
n6 -甲基腺苷（m6A）甲基转移酶rna结合基序蛋白15 （RBM15）在肝细胞癌（HCC）中的功能尚未得到充分研究。在这里，我们确定了RBM15在HCC中的临床价值、生物学功能和潜在机制。利用组织芯片和在线数据库鉴定RBM15的表达。建立了基于RBM15的风险预测模型并进行了验证。我们在体外和体内测定了RBM15对HCC细胞的生物学作用。采用RNA测序技术筛选RBM15候选靶点。随后，采用m6A点印迹法、甲基化RNA免疫沉淀qPCR、双荧光素酶报告基因法、RNA衰减法、RNA免疫沉淀qPCR等方法探讨RBM15的作用机制。我们的研究表明，RBM15在HCC中高表达，RBM15过表达表明预后较差。将RBM15与年龄和TNM分期相结合的新nomogram （nomogram）被开发并验证用于预测HCC患者的预后；我们的nomogram提高了TNM系统的预测精度。功能上，RBM15促进HCC的增殖和侵袭性。rbm15介导的m6A修饰以胰岛素样生长因子2 mrna结合蛋白1 （IGF2BP1）依赖的方式促进了YES原癌基因1 （YES1）的转录后激活。此外，YES1通过激活丝裂原活化蛋白激酶（MAPK）通路被证实是HCC细胞中的致癌基因。总之，rbm15介导的m6A修饰可能通过IGF2BP1-YES1-MAPK轴促进HCC的进展。RBM15可能是HCC预后预测中有前景的生物标志物。
The function of the N6-methyladenosine (m6A) methyltransferase RNA-binding motif protein 15 (RBM15) in hepatocellular carcinoma (HCC) has not been thoroughly investigated. Here we determined the clinical value, biological functions, and potential mechanisms of RBM15 in HCC. Expression of RBM15 was identified using tissue microarrays and online databases. A risk-prediction model based on RBM15 was developed and validated. We determined the biological role of RBM15 on HCC cells in vitro and in vivo. RNA sequencing was used to screen candidate targets of RBM15. Subsequently, the m6A dot blot assay, methylated RNA immunoprecipitation qPCR, dual-luciferase reporter assays, RNA decay assay, and RNA immunoprecipitation qPCR were employed to explore the mechanisms of RBM15. Our study showed that RBM15 was highly expressed in HCC, and overexpression of RBM15 indicated a worse outcome. A new nomogram combining RBM15 with age and TNM stage was developed and validated to predict the outcome of HCC patients; our nomogram increased the prediction accuracy of the TNM system. Functionally, RBM15 facilitates the proliferation and invasiveness of HCC. RBM15-mediated m6A modification contributed to a post-transcriptional activation of YES proto-oncogene 1 (YES1) in an insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)-dependent manner. In addition, YES1 was confirmed as an oncogene in HCC cells by activating the mitogen-activated protein kinase (MAPK) pathway. In conclusion, RBM15-mediated m6A modification might facilitate the progression of HCC via the IGF2BP1–YES1–MAPK axis. RBM15 may be a promising biomarker in the outcome prediction of HCC.
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在原发性和复发性叶绿体肿瘤中，MED12，TERT启动子和RBM15突变。
影响因子：
8.8
作者：
Garcia-Dios DA;Levi D;Shah V;Gillett C;Simpson MA;Hanby A;Tomlinson I;Sawyer EJ
通讯作者：
Sawyer EJ
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影响因子：
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作者：
Hamanaka, Natsuki;Nakanishi, Yoshito;Mio, Toshiyuki
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Mio, Toshiyuki
影响因子：
50.3
作者：
Li Z;Weng H;Su R;Weng X;Zuo Z;Li C;Huang H;Nachtergaele S;Dong L;Hu C;Qin X;Tang L;Wang Y;Hong GM;Huang H;Wang X;Chen P;Gurbuxani S;Arnovitz S;Li Y;Li S;Strong J;Neilly MB;Larson RA;Jiang X;Zhang P;Jin J;He C;Chen J
通讯作者：
Chen J
DOI：
10.1186/s13046-021-01871-4
发表时间：
2021-02-26
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Wang X;Tian L;Li Y;Wang J;Yan B;Yang L;Li Q;Zhao R;Liu M;Wang P;Sun Y
通讯作者：
Sun Y