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鉴定 LncRNA CARD8-AS1 作为肺腺癌进展的潜在预后生物标志物。

Identification of LncRNA CARD8-AS1 as a Potential Prognostic Biomarker Associated With Progression of Lung Adenocarcinoma.

机构信息

Department of Respiratory, Shanghai General Hospital - Songjiang South Campus, Shanghai, China.

Department of Respiratory, Shanghai General Hospital - Jiading Campus, Shanghai, China.

出版信息

Br J Biomed Sci. 2022 Jun 23;79:10498. doi: 10.3389/bjbs.2022.10498. eCollection 2022.

Abstract

Long non-coding RNAs (lncRNAs) exhibit crucial roles in human tumors. However, the role of lncRNA CARD8-AS1 in lung adenocarcinoma remains elusive. This study investigated the role of CARD8-AS1 in lung adenocarcinoma. The expression of CARD8-AS1 was detected by RT-qPCR analysis and confirmed using an online database. The clinical value of CARD8-AS1 was evaluated using the Kaplan-Meier curve and multivariate Cox regression analyses. The effects of CARD8-AS1 on cancer cell proliferation, migration, and invasion potential were assessed through several cellular experiments. Western blot assay was used to measure Bcl-2 and Bax protein levels. The interaction among CARD8-AS1, miR-650, and Bax, was assessed using a dual-luciferase reporter assay. The expression of CARD8-AS1 was decreased in lung adenocarcinoma tissues and cell lines ( < 0.001). Low expression of CARD8-AS1 was related to tumor size ( = 0.042), TNM stage ( = 0.021), lymph node metastasis ( = 0.025), and poor overall survival ( < 0.05). Elevated expression of CARD8-AS1 could suppress cellular viability, migration potential, and invasion ability ( < 0.05). The Bcl-2 protein levels were decreased while Bax levels were increased by overexpression of CARD8-AS1 ( < 0.001). miR-650 may thus be a direct target of CARD8-AS1 and Bax may be a direct target of miR-650. CARD8-AS1 expression was downregulated in lung adenocarcinoma and associated with several clinical parameters. CARD8-AS1 exerted tumor-suppressive effects by targeting the miR-650 and then regulating Bax expression. CARD8-AS1/miR-650 may serve as novel prognostic biomarkers and potential therapeutic targets for the treatment of lung adenocarcinoma.

摘要

长链非编码 RNA(lncRNA)在人类肿瘤中发挥着关键作用。然而,lncRNA CARD8-AS1 在肺腺癌中的作用仍不清楚。本研究探讨了 CARD8-AS1 在肺腺癌中的作用。通过 RT-qPCR 分析检测 CARD8-AS1 的表达,并使用在线数据库进行验证。通过 Kaplan-Meier 曲线和多变量 Cox 回归分析评估 CARD8-AS1 的临床价值。通过几种细胞实验评估 CARD8-AS1 对癌细胞增殖、迁移和侵袭潜力的影响。Western blot 检测 Bcl-2 和 Bax 蛋白水平。使用双荧光素酶报告基因实验评估 CARD8-AS1、miR-650 和 Bax 之间的相互作用。CARD8-AS1 在肺腺癌组织和细胞系中的表达降低(<0.001)。CARD8-AS1 低表达与肿瘤大小(=0.042)、TNM 分期(=0.021)、淋巴结转移(=0.025)和总体生存不良有关(<0.05)。CARD8-AS1 过表达可抑制细胞活力、迁移潜力和侵袭能力(<0.05)。Bcl-2 蛋白水平降低,Bax 蛋白水平升高(<0.001)。因此,miR-650 可能是 CARD8-AS1 的直接靶标,Bax 可能是 miR-650 的直接靶标。CARD8-AS1 在肺腺癌中表达下调,与多个临床参数相关。CARD8-AS1 通过靶向 miR-650 然后调节 Bax 表达发挥肿瘤抑制作用。CARD8-AS1/miR-650 可能作为肺腺癌新的预后生物标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3b9/9302548/d309e7c585b0/bjbs-79-10498-g001.jpg

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