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下调的反义长链非编码RNA促进肺腺癌的发展。

Downregulated antisense lncRNA contributes to the development of lung adenocarcinoma.

作者信息

Chiang Hung-Hsing, Ong Chai-Tung, Chang Chao-Yuan, Wu Kuan-Li, Wu Yu-Yuan, Lai Jia-Chen, Shen Tzu-Yen, Hung Jen-Yu, Lee Hsiao-Chen, Tsai Ying-Ming, Hsu Ya-Ling

机构信息

Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung 807, Taiwan.

Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University Kaohsiung 807, Taiwan.

出版信息

Am J Cancer Res. 2024 Feb 15;14(2):854-868. doi: 10.62347/THCL6758. eCollection 2024.

Abstract

The poor outcome of patients with lung adenocarcinoma (LUAD) highlights the importance to identify novel effective prognostic markers and therapeutic targets. Long noncoding RNAs (lncRNAs) have generally been considered to serve important roles in tumorigenesis and the development of various types of cancer, including LUAD. Here, we aimed to investigate the role of in LUAD and to explore its potential mechanisms by performing comprehensive bioinformatic analyses. The regulatory effect of on the expression of was validated by siRNA-based silencing. The effect of miR-421 on the modulation of was determined by miRNA mimics and inhibitors transfection. was expressed at lower levels in tumor parts and negatively correlated with unfavorable prognosis in LUAD patients. It exerted functions as a tumor suppressor gene by competitively binding to oncomir, miR-421, thereby attenuating expression. Transfection of lung cancer A549 cells with miR-421 mimics decreased the expression of . Transfection of lung cancer A549 cells with miR-421 inhibitors increased the expression of with lower cellular functions as proliferation and migration via epithelial-mesenchymal transition. In addition, inhibition of by siRNA transfection decreased the levels of , supporting the /miR-421/NR3C1 cascade. Moreover, the bioinformatic analysis also showed that could interact with the RNA-binding proteins (RBPs), CELF2 and QKI, consequently regulating RNA expression and processing. Taken together, we identified that and its indirect target can act as novel biomarkers for determining the prognosis of patients with LUAD, and further study is required.

摘要

肺腺癌(LUAD)患者的不良预后凸显了识别新型有效预后标志物和治疗靶点的重要性。长链非编码RNA(lncRNAs)通常被认为在包括LUAD在内的各种肿瘤的发生和发展中发挥重要作用。在此,我们旨在通过进行全面的生物信息学分析来研究[具体lncRNA名称未给出]在LUAD中的作用,并探索其潜在机制。通过基于小干扰RNA(siRNA)的沉默验证了[具体lncRNA名称未给出]对[另一基因名称未给出]表达的调控作用。通过转染miRNA模拟物和抑制剂确定了miR - 421对[具体lncRNA名称未给出]调控的影响。[具体lncRNA名称未给出]在肿瘤组织中表达较低,且与LUAD患者的不良预后呈负相关。它通过竞争性结合致癌miRNA miR - 421发挥肿瘤抑制基因的功能,从而减弱[另一基因名称未给出]的表达。用miR - 421模拟物转染肺癌A549细胞可降低[具体lncRNA名称未给出]的表达。用miR - 421抑制剂转染肺癌A549细胞可增加[具体lncRNA名称未给出]的表达,同时通过上皮 - 间质转化降低细胞增殖和迁移等功能。此外,通过siRNA转染抑制[具体lncRNA名称未给出]可降低[另一基因名称未给出]的水平,支持了[具体lncRNA名称未给出]/miR - 421/NR3C1级联反应。此外,生物信息学分析还表明[具体lncRNA名称未给出]可与RNA结合蛋白(RBPs)CELF2和QKI相互作用,从而调节RNA的表达和加工。综上所述,我们发现[具体lncRNA名称未给出]及其间接靶点[另一基因名称未给出]可作为判断LUAD患者预后的新型生物标志物,还需要进一步研究。

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