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环状RNA Hsa_circ_0020850沉默通过调控miR-195-5p/胰岛素受体底物2轴抑制肺腺癌发展

circRNA Hsa_circ_0020850 Silence Represses the Development of Lung Adenocarcinoma via Regulating miR-195-5p/IRS2 Axis.

作者信息

Xin Tuye, Li Shuangshuang, Zhang Ying, Kamali Xiayizha, Liu Hui, Jia Tengfei

机构信息

Department of Respiration, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, People's Republic of China.

Department of Gastrointestinal Cancer Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Oct 28;12:10679-10692. doi: 10.2147/CMAR.S257764. eCollection 2020.

Abstract

BACKGROUND

The dysregulated circular RNAs (circRNAs) are relevant to lung adenocarcinoma development. Nevertheless, the function and mechanism of hsa_circ_0020850 (circ_0020850) in lung adenocarcinoma development are uncertain.

METHODS

A total of 35 lung adenocarcinoma patients were recruited, and the tumor and normal tissue samples were harvested. A549 and PC-9 cells were exhibited for the experiments in vitro. circ_0020850, microRNA-195-5p (miR-195-5p) and insulin receptor substrate 2 (IRS2) abundances were detected via quantitative reverse transcription-polymerase chain reaction or Western blot. Cell proliferation, apoptosis, migration and invasion were measured via cell counting kit-8 (CCK8) assay, colony formation, flow cytometry, transwell and Western blot. The relationship between miR-195-5p and circ_0020850 or IRS2 was tested via dual-luciferase reporter analysis. The function of circ_0020850 on cell growth in vivo was measured via xenograft model.

RESULTS

circ_0020850 expression was enhanced in lung adenocarcinoma tissues and cells. circ_0020850 silence suppressed cell proliferation, migration and invasion and facilitated apoptosis. miR-195-5p was targeted via circ_0020850, and its knockdown reversed the inhibitive effect of circ_0020850 silence on lung adenocarcinoma development. IRS2 was targeted via miR-195-5p, and miR-195-5p inhibited cell proliferation, migration and invasion and induced apoptosis via decreasing IRS2. circ_0020850 knockdown decreased IRS2 expression via regulating miR-195-5p. circ_0020850 down-regulation decreased lung adenocarcinoma xenograft tumor growth.

CONCLUSION

circ_0020850 knockdown repressed lung adenocarcinoma cell proliferation, migration and invasion and promoted apoptosis via regulating miR-195-5p and IRS2.

摘要

背景

环状RNA(circRNAs)失调与肺腺癌发展相关。然而,hsa_circ_0020850(circ_0020850)在肺腺癌发展中的功能和机制尚不清楚。

方法

共招募35例肺腺癌患者,采集肿瘤组织和正常组织样本。体外实验采用A549和PC-9细胞。通过定量逆转录-聚合酶链反应或蛋白质免疫印迹法检测circ_0020850、微小RNA-195-5p(miR-195-5p)和胰岛素受体底物2(IRS2)的丰度。通过细胞计数试剂盒-8(CCK8)检测、集落形成、流式细胞术、Transwell实验和蛋白质免疫印迹法测量细胞增殖、凋亡、迁移和侵袭。通过双荧光素酶报告基因分析检测miR-195-5p与circ_0020850或IRS2之间的关系。通过异种移植模型检测circ_0020850对体内细胞生长的作用。

结果

circ_0020850在肺腺癌组织和细胞中表达增强。circ_0020850沉默抑制细胞增殖、迁移和侵袭,并促进细胞凋亡。circ_0020850靶向miR-195-5p,其敲低可逆转circ_0020850沉默对肺腺癌发展的抑制作用。IRS2是miR-195-5p的靶标,miR-195-5p通过降低IRS2抑制细胞增殖、迁移和侵袭并诱导细胞凋亡。circ_0020850敲低通过调节miR-195-5p降低IRS2表达。circ_0020850下调可降低肺腺癌异种移植瘤的生长。

结论

circ_0020850敲低通过调节miR-195-5p和IRS2抑制肺腺癌细胞增殖、迁移和侵袭,并促进细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158a/7604289/d6328feb1130/CMAR-12-10679-g0001.jpg

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