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circTAB2 通过海绵吸附 miR-3142 来上调 GLIS2 抑制肺癌增殖、迁移和侵袭。

circTAB2 inhibits lung cancer proliferation, migration and invasion by sponging miR-3142 to upregulate GLIS2.

机构信息

Medical College, Guangxi University, Nanning, 530004, China.

Beijing Institute of Biotechnology, Beijing, 100071, China.

出版信息

Apoptosis. 2023 Apr;28(3-4):471-484. doi: 10.1007/s10495-022-01805-1. Epub 2022 Dec 27.

Abstract

Circular RNAs (circRNAs) are a specialized circular structure, are deregulated in cancers and play essential roles in biological processes involved in tumor progression. However, the mechanism by which circRNAs affect lung tumorigenesis and progression remains largely unexplored. To investigate the role of circRNA in lung cancer, circRNA expression profile was screened by bioinformatics analysis. The levels of circTAB2, miR-3142, and GLIS family zinc finger 2 (GLIS2) were measured by quantitate real-time (qRT-PCR) or western blot. Cell proliferation, apoptosis, migration and invasion were detected by EdU, flow cytometry, and transwell assays, respectively. Bioinformatics, western blot, RIP, pull down, dual luciferase reporter and rescue experiments were used to verify the direct relationship between miR-3142 and circTAB2 or GLIS2. The xenograft assays were used to assess the role of circTAB2 in vivo.CircTAB2 exhibited low expression in cancer tissues. Gain and loss-of-function assays indicated that circTAB2 could inhibit cell proliferation, migration and invasion. Functional studies revealed that circTAB2 acted as a miRNA sponge, directly interacted with miR-3142 and consequently regulated GLIS2 /AKT. Taken together, circTAB2 serves as an inhibitory role in lung cancer through a novel circTAB2 /miR-3142 /GLIS2 /AKT pathway and could be exploited a novel marker in lung cancer.

摘要

环状 RNA(circRNAs)是一种特殊的环状结构,在癌症中失调,并在涉及肿瘤进展的生物学过程中发挥重要作用。然而,circRNAs 影响肺肿瘤发生和进展的机制在很大程度上仍未得到探索。为了研究 circRNA 在肺癌中的作用,通过生物信息学分析筛选 circRNA 表达谱。通过定量实时(qRT-PCR)或 Western blot 测量 circTAB2、miR-3142 和 GLIS 家族锌指 2(GLIS2)的水平。通过 EdU、流式细胞术和 Transwell 测定分别检测细胞增殖、凋亡、迁移和侵袭。生物信息学、Western blot、RIP、下拉、双荧光素酶报告基因和挽救实验用于验证 miR-3142 和 circTAB2 或 GLIS2 之间的直接关系。使用异种移植实验来评估 circTAB2 在体内的作用。circTAB2 在癌组织中表达水平较低。获得和功能丧失实验表明,circTAB2 可以抑制细胞增殖、迁移和侵袭。功能研究表明,circTAB2 作为 miRNA 海绵,直接与 miR-3142 相互作用,从而调节 GLIS2/AKT。总之,circTAB2 通过一种新的 circTAB2/miR-3142/GLIS2/AKT 通路在肺癌中发挥抑制作用,并且可以作为肺癌的一种新型标志物。

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