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环状RNA circ_0006089通过靶向miR-143-3p调控IGF1R表达,促进胃癌增殖、迁移和侵袭。

Circular RNA circ_0006089 regulates the IGF1R expression by targeting miR-143-3p to promote gastric cancer proliferation, migration and invasion.

作者信息

Wang Xian, Song Zhou, Meng Qingyu, Xia Shaoyou, Wang Chunxi, Huang Xiaohui

机构信息

Department of General Surgery, First Medical Center, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.

Department of General Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, China.

出版信息

Cell Cycle. 2022 May 11:1-14. doi: 10.1080/15384101.2022.2075197.

Abstract

Circular RNAs (circRNAs) figure prominently in regulating the progression of a variety of human malignancies. This study was performed to probe how circ_0006089 functioned in gastric cancer (GC). CircRNA expression profile GSE83521 was downloaded from Gene Expression Omnibus (GEO) database, and circRNAs and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure circ_0006089, microRNA-143-3p (miR-143-3p) and insulin-like growth factor 1 receptor (IGF1R) mRNA expressions in GC tissues and cell lines. Kaplan-Meier curves were used to detect the relationship between circ_0006089 expression and overall survival time of GC patients. Cell counting kit-8 (CCK-8) and 5-bromo-2-deoxyuridine (BrdU) assays were employed to detect the proliferative ability of GC cells after circ_0006089 was overexpressed or knocked down. Wound healing assay and Transwell assay were executed to examine the migration and invasion ability of GC cells. Western blot was adopted to detect IGF1R protein expressions. Circ_0006089 expression was up-regulated in GC samples and cell lines. And high circ_0006089 expression was associated with shorter survival time in GC patients. Circ_0006089 overexpression in GC cells significantly accelerated GC cell proliferation, migration and invasion, whereas circ_0006089 knockdown resulted in the opposite effects. Additionally, miR-143-3p was validated as a downstream target of circ_0006089, and circ_0006089 could positively regulate IGF1R expression via repressing miR-143-3p. Circ_0006089 is highly expressed in GC, and it promotes the malignancy of GC cells via modulating miR-143-3p/IGF1R axis, suggesting that circ_0006089 may serve as a promising therapeutic target for GC.

摘要

环状RNA(circRNAs)在调控多种人类恶性肿瘤的进展中起着重要作用。本研究旨在探究circ_0006089在胃癌(GC)中的作用机制。从基因表达综合数据库(GEO)下载circRNA表达谱GSE83521,并对circRNAs进行分析。采用定量实时聚合酶链反应(qRT-PCR)检测circ_0006089、微小RNA-143-3p(miR-143-3p)和胰岛素样生长因子1受体(IGF1R)mRNA在GC组织和细胞系中的表达。使用Kaplan-Meier曲线检测circ_0006089表达与GC患者总生存时间的关系。采用细胞计数试剂盒-8(CCK-8)和5-溴-2'-脱氧尿苷(BrdU)检测法检测circ_0006089过表达或敲低后GC细胞的增殖能力。进行伤口愈合检测和Transwell检测以检查GC细胞的迁移和侵袭能力。采用蛋白质免疫印迹法检测IGF1R蛋白表达。circ_0006089在GC样本和细胞系中表达上调。并且高circ_0006089表达与GC患者较短的生存时间相关。circ_0006089在GC细胞中的过表达显著加速了GC细胞的增殖、迁移和侵袭,而circ_0006089的敲低则产生相反的效果。此外,miR-143-3p被验证为circ_0006089的下游靶点,并且circ_0006089可通过抑制miR-143-3p正向调节IGF1R表达。circ_0006089在GC中高表达,并通过调节miR-143-3p/IGF1R轴促进GC细胞的恶性增殖,这表明circ_0006089可能是GC的一个有前景的治疗靶点。

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