SRSF2 Regulates Alternative Splicing to Drive Hepatocellular Carcinoma Development
SRSF2 Regulates Alternative Splicing to Drive Hepatocellular Carcinoma Development
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SRSF2 调节选择性剪接以驱动肝细胞癌的发展。
DOI：
10.1158/0008-5472.can-16-1919
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发表时间：
2017-03-01
期刊：
影响因子：
11.2
通讯作者：
Feng, Ying
中科院分区：
文献类型：
--
作者：
Luo, Chunling;Cheng, Yuanming;Feng, Ying
异常的 RNA 剪接被认为有助于癌症发病机制，但其潜在机制仍不清楚。在此，我们报告剪接因子 SRSF2 在人类肝细胞癌 (HCC) 中频繁上调，该事件与患者不良预后相关。 RNA-seq 和其他分子分析用于识别 SRSF2 调节的选择性剪接事件。 SRSF2 在替代外显子内的结合与其在 RNA 中的包含相关，而 SRSF2 在侧翼组成性外显子中的结合与替代外显子的排除相关。值得注意的是，在 HCC 临床标本中，SRSF2 上调的癌症相关剪接变体被发现对于肝癌细胞的发病机制和进展至关重要，其中 SRSF2 表达通过控制这些变体的表达来增加细胞增殖和致瘤潜力。我们的研究结果确定 SRSF2 是癌症中 RNA 剪接失调的关键调节因子，作为 HCC 患者的候选预后因素可能具有临床意义。癌症研究； 77(5)； 1168-78。 ©2017 AACR。
Aberrant RNA splicing is recognized to contribute to cancer pathogenesis, but the underlying mechanisms remain mainly obscure. Here, we report that the splicing factor SRSF2 is upregulated frequently in human hepatocellular carcinoma (HCC), where this event is associated with poor prognosis in patients. RNA-seq and other molecular analyses were used to identify SRSF2-regulated alternative splicing events. SRSF2 binding within an alternative exon was associated with its inclusion in the RNA, whereas SRSF2 binding in a flanking constitutive exon was associated with exclusion of the alternative exon. Notably, cancer-associated splice variants upregulated by SRSF2 in clinical specimens of HCC were found to be crucial for pathogenesis and progression in hepatoma cells, where SRSF2 expression increased cell proliferation and tumorigenic potential by controlling expression of these variants. Our findings identify SRSF2 as a key regulator of RNA splicing dysregulation in cancer, with possible clinical implications as a candidate prognostic factor in patients with HCC. Cancer Res; 77(5); 1168-78. ©2017 AACR.