Deregulated expression and subcellular localization of CPSF6, a circRNA-binding protein, promote malignant development of esophageal squamous cell carcinoma.
Deregulated expression and subcellular localization of CPSF6, a circRNA-binding protein, promote malignant development of esophageal squamous cell carcinoma.
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circRNA结合蛋白CPSF6的表达失调和亚细胞定位促进食管鳞状细胞癌的恶性发展
DOI：
10.21147/j.issn.1000-9604.2022.01.02
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发表时间：
2022-02-28
期刊：
影响因子：
--
通讯作者：
Zhan Q
中科院分区：
文献类型：
--
作者：
Guo S;Wang G;Zhao Z;Li D;Song Y;Zhan Q
切割和聚腺苷酸化特异性因子 6 (CPSF6) 已被证明是不同类型癌症中的癌蛋白。然而，CPSF6 在食管鳞状细胞癌（ESCC）中的功能尚未得到研究。在这里，我们的目的是研究 CPSF6 在 ESCC 中的潜在临床价值和生物学功能。为了确定 ESCC 患者中 CPSF6 的表达水平，我们分析了已发表的数据，进行了定量实时聚合酶链反应 (RT-qPCR) 和免疫组织化学测定。 Kaplan-Meier 曲线和对数秩检验用于生存分析。对CPSF6相关基因进行GO和KEGG分析。进行细胞增殖、集落形成和异种移植实验来验证CPSF6对ESCC的影响。此外，还进行了细胞周期和细胞凋亡测定以证实CPSF6和circCPSF6的功能。 RNA Pulldown 和放射免疫沉淀 (RIP) 测定用于确认 circCPSF6 (hsa_circ_0000417) 和 CPSF6 蛋白之间的相互作用。通过RT-qPCR确定CPSF6蛋白与circCPSF6之间的调控关系。我们发现 CPSF6 在 ESCC 组织中表达上调，并且细胞质 CPSF6 的过度表达与不良预后相关。 GO和KEGG分析表明CPSF6主要影响ESCC的细胞分裂。进一步的实验表明CPSF6在体外促进细胞增殖和集落形成。异种移植试验表明，CPSF6 的敲除显着降低了体内肿瘤生长速率。随后，我们验证了 CPSF6 的消耗会导致细胞周期停滞和细胞凋亡。最后，我们验证了 CPSF6 作为一种 circRNA 结合蛋白，与其环状同种型 circCPSF6 (hsa_circ_0000417) 相互作用并对其进行调节，其缺失还导致 ESCC 中的细胞周期停滞和细胞凋亡。 这些发现让我们认识到细胞质 CPSF6 蛋白的过度表达与 ESCC 的不良预后相关，并且 CPSF6 可能至少部分通过调节 circCPSF6 表达而发挥癌蛋白的作用。
Cleavage and polyadenylation specific factor 6 (CPSF6) has been documented as an oncoprotein in different types of cancer. However, functions of CPSF6 have not been investigated yet in esophageal squamous cell carcinoma (ESCC). Here, we aimed to investigate the potential clinical values and biological functions of CPSF6 in ESCC. For determining the expression level of CPSF6 in ESCC patients, we analyzed published data, performed quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry assays. Kaplan-Meier curves and log-rank tests were used for survival analyses. GO and KEGG analyses were done for CPSF6-related genes. Cell proliferation, colony formation and xenograft assays were conducted to verify the effects of CPSF6 on ESCC. In addition, cell cycle and apoptosis assays were also performed to manifest the functions of CPSF6 and circCPSF6. RNA pulldown and radioimmunoprecipitation (RIP) assays were used for confirming the interaction between circCPSF6 (hsa_circ_0000417) and CPSF6 protein. The regulatory relationship between CPSF6 protein and circCPSF6 was determined by RT-qPCR. We found that CPSF6 was upregulated in ESCC tissues and overexpression of cytoplasmic CPSF6 was associated with poor prognosis. GO and KEGG analyses suggested that CPSF6 could mainly affect cell division in ESCC. Further experiments manifested that CPSF6 promoted cell proliferation and colony formationin vitro. Xenograft assay showed that knockdown of CPSF6 significantly decreased tumor growth rate in vivo. Subsequently, we verified that depletion of CPSF6 led to cell cycle arrest and apoptosis. Finally, we validated that CPSF6, as a circRNA-binding protein, interacted with and regulated its circular isoform circCPSF6 (hsa_circ_0000417), of which depletion also resulted in cell cycle arrest and cell apoptosis in ESCC. These findings gave us insight that overexpression of cytoplasmic CPSF6 protein is associated with poor prognosis in ESCC and CPSF6 may function as an oncoprotein, at least in part, through regulating circCPSF6 expression.
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影响因子：
64.8
作者：
Cancer Genome Atlas Research Network;Analysis Working Group: Asan University;BC Cancer Agency;Brigham and Women’s Hospital;Broad Institute;Brown University;Case Western Reserve University;Dana-Farber Cancer Institute;Duke University;Greater Poland Cancer Centre;Harvard Medical School;Institute for Systems Biology;KU Leuven;Mayo Clinic;Memorial Sloan Kettering Cancer Center;National Cancer Institute;Nationwide Children’s Hospital;Stanford University;University of Alabama;University of Michigan;University of North Carolina;University of Pittsburgh;University of Rochester;University of Southern California;University of Texas MD Anderson Cancer Center;University of Washington;Van Andel Research Institute;Vanderbilt University;Washington University;Genome Sequencing Center: Broad Institute;Washington University in St. Louis;Genome Characterization Centers: BC Cancer Agency;Broad Institute;Harvard Medical School;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of North Carolina;University of Southern California Epigenome Center;University of Texas MD Anderson Cancer Center;Van Andel Research Institute;Genome Data Analysis Centers: Broad Institute;Brown University:;Harvard Medical School;Institute for Systems Biology;Memorial Sloan Kettering Cancer Center;University of California Santa Cruz;University of Texas MD Anderson Cancer Center;Biospecimen Core Resource: International Genomics Consortium;Research Institute at Nationwide Children’s Hospital;Tissue Source Sites: Analytic Biologic Services;Asan Medical Center;Asterand Bioscience;Barretos Cancer Hospital;BioreclamationIVT;Botkin Municipal Clinic;Chonnam National University Medical School;Christiana Care Health System;Cureline;Duke University;Emory University;Erasmus University;Indiana University School of Medicine;Institute of Oncology of Moldova;International Genomics Consortium;Invidumed;Israelitisches Krankenhaus Hamburg;Keimyung University School of Medicine;Memorial Sloan Kettering Cancer Center;National Cancer Center Goyang;Ontario Tumour Bank;Peter MacCallum Cancer Centre;Pusan National University Medical School;Ribeirão Preto Medical School;St. Joseph’s Hospital &Medical Center;St. Petersburg Academic University;Tayside Tissue Bank;University of Dundee;University of Kansas Medical Center;University of Michigan;University of North Carolina at Chapel Hill;University of Pittsburgh School of Medicine;University of Texas MD Anderson Cancer Center;Disease Working Group: Duke University;Memorial Sloan Kettering Cancer Center;National Cancer Institute;University of Texas MD Anderson Cancer Center;Yonsei University College of Medicine;Data Coordination Center: CSRA Inc.;Project Team: National Institutes of Health
通讯作者：
Project Team: National Institutes of Health
DOI：
10.21147/j.issn.1000-9604.2020.06.09
发表时间：
2020-12-31
期刊：
Chinese journal of cancer research = Chung-kuo yen cheng yen chiu
影响因子：
--
作者：
Li M;Shao D;Zhou J;Gu J;Qin J;Chen W;Wei W
通讯作者：
Wei W
starBase v2.0：从大规模 CLIP-Seq 数据中解码 miRNA-ceRNA、miRNA-ncRNA 和蛋白质-RNA 相互作用网络
影响因子：
14.9
作者：
Li JH;Liu S;Zhou H;Qu LH;Yang JH
通讯作者：
Yang JH
影响因子：
24.5
作者：
Li J;Chen Z;Tian L;Zhou C;He MY;Gao Y;Wang S;Zhou F;Shi S;Feng X;Sun N;Liu Z;Skogerboe G;Dong J;Yao R;Zhao Y;Sun J;Zhang B;Yu Y;Shi X;Luo M;Shao K;Li N;Qiu B;Tan F;Chen R;He J
通讯作者：
He J
影响因子：
44.1
作者：
Cui Y;Chen H;Xi R;Cui H;Zhao Y;Xu E;Yan T;Lu X;Huang F;Kong P;Li Y;Zhu X;Wang J;Zhu W;Wang J;Ma Y;Zhou Y;Guo S;Zhang L;Liu Y;Wang B;Xi Y;Sun R;Yu X;Zhai Y;Wang F;Yang J;Yang B;Cheng C;Liu J;Song B;Li H;Wang Y;Zhang Y;Cheng X;Zhan Q;Li Y;Liu Z
通讯作者：
Liu Z