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Nat Cell Biol:第二军医大孙树汉教授研究组找到新促癌因子

摘要 : 2017年5月29日,国际学术权威刊物自然出版集团旗下子刊《Nature Cell Biology》杂志上在线发表了第二军医大学医学遗传学教研室孙树汉教授研究组题为“The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1”的研究论文

2017年5月29日,国际学术权威刊物自然出版集团旗下子刊《Nature Cell Biology》杂志上在线发表了第二军医大学医学遗传学教研室孙树汉教授研究组题为“The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1”的研究论文,论文报道了MBNL3这剪接因子能促进癌症发生,导致肝细胞癌HCC患者预后不良,表明了剪接因子和剪接事件可以作为潜在的治疗靶点。

文章中,研究人员发现一种剪接因子:MBNL3能促进癌症发生,导致肝细胞癌HCC患者预后不良。研究人员发现敲除MBNL3几乎完全能消除肝细胞癌肿瘤发生,这对于肝细胞癌患者来说无疑是一个福音。肝细胞癌(Hepatocellular carcinoma, HCC)是目前我国致死率居第二位的恶性肿瘤,侵袭力强,易转移,预后差,五年预后存活率仅有10~20%。

MBNL属于Muscleblind样蛋白(muscleblind-like proteins,MBNL),之前的研究显示这种蛋白在肌肉和眼睛的发育过程中发挥了重要的功能,而最新研究通过转录组分析表明,MBNL3能诱导lncRNA-PXN-AS1 4号外显子增加,这也表明了lncRNA在其中扮演的作用。

这项研究总体来说将剪接因子,剪接事件与肿瘤发生,以及lncRNA联系在了一起,表明了剪接因子和剪接事件可以作为潜在的治疗靶点。

原文链接:

The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1

原文摘要:

Understanding the roles of splicing factors and splicing events during tumorigenesis would open new avenues for targeted therapies. Here we identify an oncofetal splicing factor, MBNL3, which promotes tumorigenesis and indicates poor prognosis of hepatocellular carcinoma patients. MBNL3 knockdown almost completely abolishes hepatocellular carcinoma tumorigenesis. Transcriptomic analysis revealed that MBNL3 induces lncRNA-PXN-AS1 exon 4 inclusion. The transcript lacking exon 4 binds to coding sequences of PXN mRNA, causes dissociation of translation elongation factors from PXN mRNA, and thereby inhibits PXN mRNA translation. In contrast, the transcript containing exon 4 preferentially binds to the 3′ untranslated region of PXN mRNA, protects PXN mRNA from microRNA-24–AGO2 complex-induced degradation, and thereby increases PXN expression. Through inducing exon 4 inclusion, MBNL3 upregulates PXN, which mediates the pro-tumorigenic roles of MBNL3. Collectively, these data demonstrate detailed mechanistic links between an oncofetal splicing factor, a splicing event and tumorigenesis, and establish splicing factors and splicing events as potential therapeutic targets.

来源: Nature Cell Biology 浏览次数:0

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