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Circ_0028826通过充当miR-758-3p的海绵以解除对异柠檬酸脱氢酶2(IDH2)表达的抑制,从而促进非小细胞肺癌的生长和转移。

Circ_0028826 Promotes Growth and Metastasis of NSCLC via Acting as a Sponge of miR-758-3p to Derepress IDH2 Expression.

作者信息

Guo Lihong, Liu Xueqin, Zhang Jie, Liu Zhuixing, Zhang Bohao, Sun Yang, Cui Dandan, Liu Jinpeng

机构信息

Department of Oncology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi, China.

出版信息

Clin Respir J. 2024 Aug;18(8):e13802. doi: 10.1111/crj.13802.

Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) is one of the cancers with the highest mortality and morbidity in the world. Circular RNAs (circRNAs) are newly identified players in carcinogenesis and development of various cancers. This study is aimed at exploring the functional effects and mechanism of circ_0028826 in the development of NSCLC.

METHODS

Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of circ_0028826, IDH2 mRNA, and miR-758-3p. IDH2, Bcl2, Bax, and E-cadherin protein levels were detected using a western blot. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, and transwell assays were used to assess the capacities of proliferation, apoptosis, migration, and invasion. Interaction between miR-758-3p and circ_0028826 or IDH2 was validated using a dual-luciferase reporter assay. The role of circ_0028826 in vivo was checked based on a xenograft tumor model.

RESULTS

Circ_0028826 was elevated in NSCLC, and its absence inhibited NSCLC cell proliferation, migration, invasion, and induced apoptosis. In terms of mechanism, circ_0028826 increased IDH2 expression by targeting miR-758-3p. In addition, circ_0028826 knockdown also regulated IDH2 by targeting miR-758-3p to inhibit tumor growth in vivo.

CONCLUSION

Circ_0028826 promoted the development of NSCLC via regulation of the miR-758-3p/IDH2 axis, providing a new strategy for NSCLC treatment.

摘要

背景

非小细胞肺癌(NSCLC)是全球死亡率和发病率最高的癌症之一。环状RNA(circRNAs)是在各种癌症的发生和发展中新发现的参与者。本研究旨在探讨circ_0028826在NSCLC发生发展中的功能作用及机制。

方法

采用实时定量PCR(RT-qPCR)检测circ_0028826、异柠檬酸脱氢酶2(IDH2)mRNA和miR-758-3p的表达水平。使用蛋白质免疫印迹法检测IDH2、Bcl-2、Bax和E-钙黏蛋白的蛋白水平。采用细胞计数试剂盒-8(CCK-8)、5-乙炔基-2'-脱氧尿苷(EdU)、流式细胞术、伤口愈合实验和Transwell实验评估细胞的增殖、凋亡、迁移和侵袭能力。使用双荧光素酶报告基因实验验证miR-758-3p与circ_0028826或IDH2之间的相互作用。基于异种移植肿瘤模型检测circ_0028826在体内的作用。

结果

circ_0028826在NSCLC中表达升高,缺失circ_0028826可抑制NSCLC细胞的增殖、迁移、侵袭并诱导细胞凋亡。机制方面,circ_0028826通过靶向miR-758-3p增加IDH2的表达。此外,敲低circ_0028826还通过靶向miR-758-3p调节IDH2,从而抑制体内肿瘤生长。

结论

circ_0028826通过调控miR-758-3p/IDH2轴促进NSCLC的发展,为NSCLC治疗提供了新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a93/11306285/c63b3c49a45d/CRJ-18-e13802-g002.jpg

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