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

IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM
Lihong Guo, Xueqin Liu, Jie Zhang, Zhuixing Liu, Bohao Zhang, Yang Sun, Dandan Cui, Jinpeng Liu
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引用次数: 0

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.

Abstract Image

Circ_0028826 通过充当 miR-758-3p 的海绵来抑制 IDH2 的表达,从而促进 NSCLC 的生长和转移。
背景:非小细胞肺癌(NSCLC非小细胞肺癌(NSCLC)是世界上死亡率和发病率最高的癌症之一。环状 RNA(circRNA)是新发现的在各种癌症的发生和发展中起作用的因子。本研究旨在探讨 circ_0028826 在 NSCLC 发病过程中的功能作用和机制:方法:采用实时定量 PCR(RT-qPCR)技术检测 circ_0028826、IDH2 mRNA 和 miR-758-3p 的表达水平。用 Western 印迹法检测 IDH2、Bcl2、Bax 和 E-cadherin 蛋白水平。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、伤口愈合和透孔试验被用来评估细胞的增殖、凋亡、迁移和侵袭能力。使用双荧光素酶报告实验验证了 miR-758-3p 与 circ_0028826 或 IDH2 之间的相互作用。通过异种移植肿瘤模型检验了circ_0028826在体内的作用:结果:Circ_0028826在NSCLC中升高,其缺失可抑制NSCLC细胞的增殖、迁移和侵袭,并诱导细胞凋亡。在机制方面,circ_0028826通过靶向miR-758-3p增加了IDH2的表达。此外,circ_0028826敲除后还能通过靶向miR-758-3p调节IDH2,从而抑制体内肿瘤的生长:Circ_0028826通过调控miR-758-3p/IDH2轴促进了NSCLC的发展,为NSCLC的治疗提供了一种新策略。
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来源期刊
Clinical Respiratory Journal
Clinical Respiratory Journal 医学-呼吸系统
CiteScore
3.70
自引率
0.00%
发文量
104
审稿时长
>12 weeks
期刊介绍: Overview Effective with the 2016 volume, this journal will be published in an online-only format. Aims and Scope The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic. We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including: Asthma Allergy COPD Non-invasive ventilation Sleep related breathing disorders Interstitial lung diseases Lung cancer Clinical genetics Rhinitis Airway and lung infection Epidemiology Pediatrics CRJ provides a fast-track service for selected Phase II and Phase III trial studies. Keywords Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)
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