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环状非编码RNA NOLC1通过结合ESRP1并调节CDK1和RhoA的表达促进上皮性卵巢癌的肿瘤发生和进展。

Circ-NOLC1 promotes epithelial ovarian cancer tumorigenesis and progression by binding ESRP1 and modulating CDK1 and RhoA expression.

作者信息

Chen Shuo, Wu Wu, Li Qian-Hui, Xie Bu-Min, Shen Fan, Du Yu-Ping, Zong Zhi-Hong, Wang Li-Li, Wei Xiao-Qing, Zhao Yang

机构信息

Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.

Department of Obstetrics and Gynecology, Center for Reproductive Medicine/Department of Fetal Medicine and Prenatal Diagnosis, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.

出版信息

Cell Death Discov. 2021 Jan 22;7(1):22. doi: 10.1038/s41420-020-00381-0.

Abstract

Circular RNAs (circRNAs) play important roles in cancer tumorigenesis and progression, representing prognostic biomarkers and therapeutic targets. In this case, we demonstrated the role of circ-NOLC1 in epithelial ovarian cancer (EOC). Our results have shown that Circ-NOLC1 expression was higher in EOC tissues than in normal tissues, and was positively associated with FIGO stage, differentiation. Among ovarian cancer cell lines, circ-NOLC1 expression was the highest in A2780, and lowest in CAOV3. Overexpression of circ-NOLC1 in CAOV3 cells increased cell proliferation, migration, and invasion ability, whereas silencing of circ-NOLC1 in A2780 cells had the opposite effect: however, neither circ-NOLC1 downregulation nor overexpression influenced NOLC1 mRNA expression. In nude mice with subcutaneous tumors, circ-NOLC1 downregulation decreased tumor growth. Bioinformatic analysis and RNA-binding protein immunoprecipitation showed that circ-NOLC1 could bind to ESRP1. In addition, the overexpression of circ-NOLC1 significantly increased ESRP1, RhoA, and CDK1 protein and mRNA expression level; circ-NOLC1 downregulation had the opposite effects. The tumor-promoting effect of circ-NOLC1 was inhibited by knockdown of ESRP1, CDK1, or RhoA expression in circ-NOLC1-overexpressing cells, which might act by modulating RhoA and CDK1 expression. In conclusion, our study demonstrated that Circ-NOLC1 might promote EOC tumorigenesis and development by binding ESRP1 and modulating CDK1 and RhoA expression.

摘要

环状RNA(circRNAs)在癌症的发生和发展中发挥着重要作用,是预后生物标志物和治疗靶点。在此,我们阐述了circ-NOLC1在上皮性卵巢癌(EOC)中的作用。我们的结果表明,circ-NOLC1在EOC组织中的表达高于正常组织,且与国际妇产科联盟(FIGO)分期、分化呈正相关。在卵巢癌细胞系中,circ-NOLC1在A2780细胞中的表达最高,在CAOV3细胞中最低。在CAOV3细胞中过表达circ-NOLC1可增强细胞增殖、迁移和侵袭能力,而在A2780细胞中沉默circ-NOLC1则产生相反的效果:然而,circ-NOLC1的下调或过表达均不影响NOLC1 mRNA的表达。在皮下接种肿瘤的裸鼠中,circ-NOLC1的下调可抑制肿瘤生长。生物信息学分析和RNA结合蛋白免疫沉淀显示,circ-NOLC1可与ESRP1结合。此外,circ-NOLC1的过表达显著增加了ESRP1、RhoA和CDK1蛋白及mRNA的表达水平;circ-NOLC1的下调则产生相反的效果。在circ-NOLC1过表达的细胞中,敲低ESRP1、CDK1或RhoA的表达可抑制circ-NOLC1的促肿瘤作用,这可能是通过调节RhoA和CDK1的表达来实现的。总之,我们的研究表明,circ-NOLC1可能通过结合ESRP1并调节CDK1和RhoA的表达来促进EOC的发生和发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2d7/7822960/b979b3b6140b/41420_2020_381_Fig1_HTML.jpg

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