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论文题目: SRSF2 Regulates Alternative Splicing to Drive Hepatocellular Carcinoma Development
英文论文题目: SRSF2 Regulates Alternative Splicing to Drive Hepatocellular Carcinoma Development
第一作者: Luo, CL; Cheng, YM; Liu, YG; Chen, LL; Liu, LN; Wei, N; Xie, ZQ; Wu, WW; Feng, Y
英文第一作者: Luo, CL; Cheng, YM; Liu, YG; Chen, LL; Liu, LN; Wei, N; Xie, ZQ; Wu, WW; Feng, Y
联系作者: Feng, Y (reprint author), Chinese Acad Sci, Inst Nutr Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Feng, Y (reprint author), Chinese Acad Sci, Inst Nutr Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2017
卷: 77
期: 5
页码: 1168-1178
摘要: 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.
英文摘要: 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.
刊物名称: CANCER RESEARCH
英文刊物名称: CANCER RESEARCH
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学科: Oncology
英文学科: Oncology
影响因子: 9.122
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论文类别: Article
英文论文类别: Article
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