李晶,岳婷,平伟,向春华.基于生物信息学探讨REG4对肺腺癌A549、H1299细胞增殖、迁移的影响机制.[J].中南医学科学杂志.,2025,(2):195-200. |
基于生物信息学探讨REG4对肺腺癌A549、H1299细胞增殖、迁移的影响机制 |
Exploring the mechanism of the influences of REG4 on the proliferation and migration of lung adenocarcinoma A549, H1299 cells based on bioinformatics |
投稿时间:2024-09-17 修订日期:2025-01-14 |
DOI:10.15972/j.cnki.43-1509/r.2025.02.002 |
中文关键词: LUAD REG4 生物信息学 [ |
英文关键词:LUAD REG4 bioinformatics A549 cell H1299 cell cell proliferation cell migration |
基金项目:国家自然科学基金青年基金(81902347) |
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中文摘要: |
目的基于生物信息学探讨REG4对肺腺癌(LUAD)A549、H1299细胞增殖、迁移的影响机制。 方法从UCSC下载泛癌数据集;从GEO数据库中下载4个成人LUAD芯片数据集(GSE27262、GSE116959、GSE32863、GSE31210)。比较REG4在各数据集癌组织和癌旁组织中的表达水平。STRING数据库构建PPI网络,Cytoscape软件提取REG4相关基因,KEGG分析REG4相关信号通路。取本院临床标本进行验证。将LUAD细胞株A549细胞、H1299细胞随机分为小干扰RNA阴性(对照)组和si-REG4(沉默)组,qRT-PCR检测细胞REG4 mRNA表达。CCK-8检测各组细胞增殖能力,流式细胞术检测各组凋亡率,Transwell检测各组细胞迁移能力。Western blotting检测REG4、磷脂酰肌醇3激酶(P13K)和丝氨酸/苏氨酸激酶(Akt)及其磷酸化蛋白的表达。 结果数据集癌组织中REG4表达水平高于癌旁组织。KEGG通路主要富集于PI3K/Akt信号通路。临床验证结果与数据集结果一致。LUAD细胞株A549细胞、H1299细胞中REG4呈高表达(P<0.05)。与对照组相比,沉默组A549细胞、H1299细胞REG4蛋白表达水平以及细胞增殖、迁移能力降低(P<0.05),细胞凋亡率升高(P<0.05)。REG4靶向正调控p-PI3K、p-Akt表达。 结论基于生物信息学和临床验证明确REG4在LUAD中高表达,沉默REG4对A549、H1299细胞增殖、迁移具有抑制作用,对细胞凋亡具有促进作用,可能与通过抑制PI3K、Akt磷酸化有关。 |
英文摘要: |
AimTo explore the mechanism of the influences of REG4 on the proliferation and migration of lung adenocarcinoma (LUAD) A549, H1299 cells based on bioinformatics. MethodsPan-cancer data were downloaded from UCSC. Four sets of adult LUAD microarray datasets (GSE27262, GSE116959, GSE32863, GSE31210) were obtained from the GEO database. The expression levels of REG4 in cancer tissues and adjacent tissues across different datasets were compared. A PPI network was constructed by using the STRING database, and REG4-associated proteins were analyzed by using Cytoscape software. KEGG pathway analysis was performed to identify the signaling pathways associated with REG4. Validation was performed by using clinical data from our hospital. LUAD cell lines (A549 and H1299) were divided into siRNA-negative (control) and si-REG4 (silence) groups. REG4 mRNA expression was detected via qRT-PCR. Cell proliferation, apoptosis rates and migration ability were assessed by CCK-8 assay, flow cytometry, and Transwell assay, respectively. Western blotting was applied to measure the protein expression of REG4, phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase (Akt), and their phosphorylated proteins. ResultsREG4 expression was higher in tumor tissues than in adjacent tissues across all datasets. KEGG analysis revealed enrichment in the PI3K/Akt signaling pathway. Clinical validation results aligned with the datasets findings. REG4 was highly expressed in LUAD cell lines A549 and H1299 cells (P<0.05). In silence groups, REG4 protein expression and cell proliferation, migration ability were decreased (P<0.05), while cell apoptosis rates were increased (P<0.05). REG4 positively regulated p-PI3K and p-Akt expression. ConclusionBased on bioinformatics and clinical validation, it is clear that REG4 is highly expressed in LUAD. Silencing REG4 has inhibitory effects on A549, H1299 cell proliferation and migration, and promotes cell apoptosis, which may be related to the inhibition of PI3K and Akt phosphorylation. |
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