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环状RNA Circ_0002762通过激活RelA/核因子κB(Nf-κB)信号通路促进宫颈鳞状细胞癌的细胞迁移和侵袭。

Circular RNA Circ_0002762 promotes cell migration and invasion in cervical squamous cell carcinoma via activating RelA/nuclear factor kappa B (Nf-kB) signalling pathway.

作者信息

Ji Lei, Chen Youguo, Chen Xiaoping

机构信息

Department of Obstetrics and Gynecology, Yancheng First People's Hospital of Jiangsu Province, Yancheng, Jiangsu, China.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

出版信息

RNA Biol. 2025 Dec;22(1):1-13. doi: 10.1080/15476286.2025.2478539. Epub 2025 Mar 24.

Abstract

Cervical cancer is a leading cause of cancer-related deaths, with cervical squamous cell carcinoma (CSCC) accounting for a majority of cases. Circular RNAs (circRNAs) have been repeatedly suggested as crucial effectors in modulating the development of multiple malignancies. The expression of circ_0002762 was predicted to be high in CSCC tissues in GEO dataset, but the functional role and underlying regulatory mechanism of circ_0002762 in CSCC was unclear. By series of functional assays and mechanism assays, supported by bioinformatics analysis, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis and western blot assays, we identified that circ_0002762 aberrantly up-regulated in CSCC, promoting CSCC cell migration and invasion. Mechanically, circ_0002762 was transcriptionally activated by Fork head box A1 (FOXA1). Moreover, the involvement of nuclear factor kappa B (NF-kB) signalling in circ_0002762 regulation mechanism in CSCC cells was ascertained. Additionally, circ_0002762, predominantly accumulated in cell cytoplasm, was proved to recruit Mov10 RISC complex RNA helicase (MOV10) to enhance RelA mRNA stability, thus affecting CSCC cell migration and invasion. In summary, FOXA1-mediated circ_0002762 up-regulation could enhance the migratory and invasive abilities of CSCC cells via the MOV10/RelA/NF-kB pathway.

摘要

宫颈癌是癌症相关死亡的主要原因,其中宫颈鳞状细胞癌(CSCC)占大多数病例。环状RNA(circRNA)一再被认为是调节多种恶性肿瘤发生发展的关键因子。在GEO数据集中预测circ_0002762在CSCC组织中的表达较高,但circ_0002762在CSCC中的功能作用和潜在调控机制尚不清楚。通过一系列功能实验和机制实验,并得到生物信息学分析、逆转录定量实时聚合酶链反应(RT-qPCR)分析和蛋白质免疫印迹实验的支持,我们发现circ_0002762在CSCC中异常上调,促进CSCC细胞迁移和侵袭。机制上,circ_0002762由叉头框A1(FOXA1)转录激活。此外,还确定了核因子κB(NF-κB)信号通路参与CSCC细胞中circ_0002762的调控机制。此外,主要积聚在细胞质中的circ_0002762被证明可募集Mov10 RNA诱导沉默复合体解旋酶(MOV10)以增强RelA mRNA稳定性,从而影响CSCC细胞迁移和侵袭。总之,FOXA1介导的circ_0002762上调可通过MOV10/RelA/NF-κB途径增强CSCC细胞的迁移和侵袭能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb4a/11934174/6f6f89a1409e/KRNB_A_2478539_UF0001_OC.jpg

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