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环状RNA Circ_0013958通过调控miR-637/PLXNB2轴在卵巢癌中发挥肿瘤促进作用。

Circular RNA Circ_0013958 Functions as a Tumor Promoter in Ovarian Cancer by Regulating miR-637/PLXNB2 Axis.

作者信息

Liang Yanfei, Meng Kaiyi, Qiu Rui

机构信息

Department of Gynecology, The Second Nanning People's Hospital, Nanning, China.

出版信息

Front Genet. 2021 Jul 21;12:644451. doi: 10.3389/fgene.2021.644451. eCollection 2021.

Abstract

Circular RNAs (circRNAs) have emerged as important regulators in diverse human malignancies, including ovarian cancer (OC). This study was performed to explore the function and regulatory mechanism underlying circ_0013958 in OC progression. Quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay was applied to examine the expression of circ_0013958, microRNA-637 (miR-637), and Plexin B2 (PLXNB2). The target relationship between miR-637 and circ_0013958 or PLXNB2 was verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. Cell Counting Kit-8 (CCK-8) and colony formation assays were employed to detect cell viability and clonogenicity ability, respectively. Cell migration and invasion were analyzed by Transwell assay. Cell apoptosis was monitored by flow cytometry. The role of circ_0013958 was determined by xenograft tumor assay. Circ_0013958 and PLXNB2 were upregulated, while miR-637 was downregulated in OC tissues and cells. Circ_0013958 acted as a sponge for miR-637 to regulate the expression of PLXNB2 in OC cells. The repression effects of circ_0013958 knockdown on cell proliferation, migration, invasion, and apoptosis in OC cells were partly attenuated by the miR-637 inhibitor. And miR-637 targeted PLXNB2 to suppress OC cell proliferation, migration, and invasion. Moreover, circ_0013958 silencing blocked OC tumor growth . Circ_0013958 knockdown impeded OC development through modulating the miR-637/PLXNB2 axis, highlighting a therapeutic target for OC.

摘要

环状RNA(circRNAs)已成为包括卵巢癌(OC)在内的多种人类恶性肿瘤中的重要调节因子。本研究旨在探讨circ_0013958在OC进展中的功能及调控机制。采用定量实时聚合酶链反应(qRT-PCR)或蛋白质免疫印迹法检测circ_0013958、微小RNA-637(miR-637)和丛状蛋白B2(PLXNB2)的表达。通过双荧光素酶报告基因检测或RNA免疫沉淀(RIP)实验验证miR-637与circ_0013958或PLXNB2之间的靶向关系。分别采用细胞计数试剂盒-8(CCK-8)和集落形成实验检测细胞活力和克隆形成能力。通过Transwell实验分析细胞迁移和侵袭能力。采用流式细胞术监测细胞凋亡。通过异种移植瘤实验确定circ_0013958的作用。在OC组织和细胞中,circ_0013958和PLXNB2上调,而miR-637下调。circ_0013958作为miR-637的海绵,调节OC细胞中PLXNB2的表达。miR-637抑制剂部分减弱了circ_0013958敲低对OC细胞增殖、迁移、侵袭和凋亡的抑制作用。并且miR-637靶向PLXNB2以抑制OC细胞增殖、迁移和侵袭。此外,circ_0013958沉默可阻止OC肿瘤生长。circ_0013958敲低通过调节miR-637/PLXNB2轴阻碍OC发展,突出了OC的一个治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8334736/2d8126da59af/fgene-12-644451-g0001.jpg

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