Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma.
Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma.
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肝细胞癌中裂解和多腺苷酸化特异性因子 1 通过选择性多腺苷酸化和剪接促进肿瘤进展
DOI：
10.3389/fcell.2021.616835
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发表时间：
2021
影响因子：
5.5
通讯作者：
Yun JP
中科院分区：
文献类型：
--
作者：
Chen SL;Zhu ZX;Yang X;Liu LL;He YF;Yang MM;Guan XY;Wang X;Yun JP
选择性多聚腺苷酸化（阿帕）是mRNA 3′非翻译区（3′ UTR）切割和多聚腺苷酸化（CPA）的重要转录后调控机制。在肝细胞癌（HCC）中报告了几例异常阿帕事件。然而，阿帕背后的调控机制仍不清楚。在这项研究中，我们发现，裂解和多聚腺苷酸化特异性因子1（CPSF 1）的表达，CPA复合物的主要组成部分，在肝癌组织中显着增加，并与不利的生存结果。CPSF 1的敲低抑制HCC细胞增殖和迁移，而CPSF 1的过表达引起相反的效果。基于对HepG2.2.15细胞的Iso-Seq和RNA-seq数据的综合分析，我们鉴定了一系列在CPSF 1敲低后具有差异3′ UTR长度的转录物。这些转录本与基因转录、细胞骨架维持和内膜系统运输等生物学功能有关。此外，敲除CPSF 1诱导增加选择性剪接（AS）事件除了阿帕。总之，这项研究为我们理解HCC的转录后调控机制提供了新的见解，并暗示CPSF 1可能是HCC的潜在预后生物标志物和治疗靶点。
Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism required for cleavage and polyadenylation (CPA) of the 3′ untranslated region (3′ UTR) of mRNAs. Several aberrant APA events have been reported in hepatocellular carcinoma (HCC). However, the regulatory mechanisms underlying APA remain unclear. In this study, we found that the expression of cleavage and polyadenylation specific factor 1 (CPSF1), a major component of the CPA complex, was significantly increased in HCC tissues and correlated with unfavorable survival outcomes. Knockdown of CPSF1 inhibited HCC cell proliferation and migration, whereas overexpression of CPSF1 caused the opposite effect. Based on integrative analysis of Iso-Seq and RNA-seq data from HepG2.2.15 cells, we identified a series of transcripts with differential 3′ UTR lengths following the knockdown of CPSF1. These transcripts were related to the biological functions of gene transcription, cytoskeleton maintenance, and endomembrane system transportation. Moreover, knockdown of CPSF1 induced an increase in alternative splicing (AS) events in addition to APA. Taken together, this study provides new insights into our understanding of the post-transcriptional regulatory mechanisms in HCC and implies that CPSF1 may be a potential prognostic biomarker and therapeutic target for HCC.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Lee SH;Singh I;Tisdale S;Abdel-Wahab O;Leslie CS;Mayr C
通讯作者：
Mayr C
影响因子：
10.5
作者：
Lutz, CS;Murthy, KGK;Alwine, JC
通讯作者：
Alwine, JC
影响因子：
7.3
作者：
Martinson, Harold G.
通讯作者：
Martinson, Harold G.