ANLN的下调通过焦亡激活抑制肺腺癌的进展。

IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Molecular medicine reports Pub Date : 2023-09-01 DOI:10.3892/mmr.2023.13064
Li Sheng, Yanhai Kang, Denglin Chen, Linyang Shi
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引用次数: 1

摘要

肺腺癌(LUAD)的分子靶向治疗取得了重大进展。然而,复杂的分子模式和LUAD的高度异质性限制了这些疗法对特定患者亚群的疗效;因此,有必要探索新的LUAD治疗靶点。应用基因表达谱交互分析数据库分析anillin (ANLN)在LUAD中的表达水平。此外,使用Kaplan - Meier绘图仪评估ANLN基因表达与患者生存结果之间的关系。随后,在A549和H1299细胞系中转染小干扰RNA (small interfering RNA, siRNA)敲低ANLN,然后分别进行TUNEL、集落形成和Transwell实验,评估细胞死亡、集落形成和迁移。此外,采用western blot分析ANLN敲除后caspase - 1、白细胞介素(IL - 18)、IL - 1β、NLR家族pyrin结构域3 (NLRP3)、凋亡相关斑点样蛋白(含有CARD结构域ASC)和裂解气皮蛋白D (GSDMD)的表达水平。结果显示,与邻近正常样本相比,LUAD组织中ANLN mRNA的表达显著增加。随着临床分期的推进,ANLN的表达水平呈上升趋势。此外,与低ANLN表达水平的患者相比,高ANLN表达水平的患者表现出较差的总生存率。随后的ANLN敲除实验表明,A549和H1299细胞的细胞死亡率升高,集落形成和迁移减少。此外,ANLN敲低导致A549和H1299细胞中焦亡相关分子的蛋白表达水平升高,包括caspase - 1、NLRP3、cleaved - GSDMD、IL - 1β、ASC和IL - 18。综上所述,ANLN是LUAD的一个重要基因和一个有希望的治疗靶点。它作为治疗靶点的潜力使其成为进一步探索LUAD新治疗策略的有趣候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Knockdown of ANLN inhibits the progression of lung adenocarcinoma via pyroptosis activation.

Significant advancements have been achieved in the area of molecular targeted therapy for lung adenocarcinoma (LUAD). However, the complex molecular patterns and high heterogeneity of LUAD confine the efficacy of these therapies to a specific subset of patients; therefore, it is necessary to explore novel targets for LUAD treatment. The expression levels of anillin (ANLN) in LUAD were analyzed using the Gene Expression Profiling Interactive Analysis database. Furthermore, the association between ANLN gene expression and patient survival outcomes was evaluated using the Kaplan‑Meier Plotter. Subsequently, small interfering RNA (siRNA) transfection was performed to knock down ANLN in A549 and H1299 cell lines, after which, TUNEL, colony formation and Transwell assays were conducted to assess cell death, colony formation and migration, respectively. Additionally, western blot analysis was performed to analyze the expression levels of caspase‑1, interleukin (IL)‑18 (IL‑18), IL‑1β, NLR family pyrin domain‑containing 3 (NLRP3), apoptosis‑associated speck‑like protein containing a CARD domain (ASC) and cleaved gasdermin D (GSDMD) following ANLN knockdown. The results revealed that ANLN mRNA expression was significantly increased in LUAD tissues compared with adjacent normal samples. Furthermore, the expression levels of ANLN displayed an increasing trend with advancing clinical stage. Furthermore, patients with high ANLN expression levels exhibited poor overall survival rates compared with those with low ANLN expression levels. Subsequent ANLN knockdown experiments indicated elevated cell death rate, and reduced colony formation and migration in both A549 and H1299 cells. Additionally, ANLN knockdown resulted in increased protein expression levels of pyroptosis‑associated molecules, including caspase‑1, NLRP3, cleaved‑GSDMD, IL‑1β, ASC and IL‑18 in both A549 and H1299 cells. In conclusion, ANLN represents an important gene and a promising therapeutic target for LUAD. Its potential as a therapeutic target makes it an interesting candidate for further exploration in the development of novel treatment strategies for LUAD.

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来源期刊
Molecular medicine reports
Molecular medicine reports 医学-病理学
CiteScore
7.60
自引率
0.00%
发文量
321
审稿时长
1.5 months
期刊介绍: Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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