关键词: Bioinformatics Envelope protein LUAD PBM SARS-CoV-1

来  源:   DOI:10.1016/j.micinf.2024.105381

Abstract:
BACKGROUND: In both lung adenocarcinoma (LUAD) and severe acute respiratory syndrome (SARS), uncontrolled inflammation can be detected in lung tissue. The PDZ-binding motif (PBM) in the SARS-CoV-1 E protein has been demonstrated to be a virulence factor that induces a cytokine storm.
METHODS: To identify gene expression fluctuations induced by PBM, microarray sequencing data of lung tissue infected with wild-type (SARS-CoV-1-E-wt) or recombinant virus (SARS-CoV-1-E-mutPBM) were analyzed, followed by functional enrichment analysis. To understand the role of the screened genes in LUAD, overall survival and immune correlation were calculated.
RESULTS: A total of 12 genes might participate in the initial and developmental stages of LUAD through expression variation and mutation. Moreover, dysregulation of a total of 12 genes could lead to a poorer prognosis. In addition, the downregulation of MAMDC2 and ITGA8 by PBM could also affect patient prognosis. Although the conserved PBM (-D-L-L-V-) can be found at the end of the carboxyl terminus in multiple E proteins of coronaviruses, the specific function of each protein depends on the entire amino acid sequence.
CONCLUSIONS: In summary, PBM containing the SARS-CoV-1 E protein promoted the carcinogenesis of LUAD by dysregulating important gene expression profiles and subsequently influencing the immune response and overall prognosis.
摘要:
背景:在肺腺癌(LUAD)和严重急性呼吸综合征(SARS)中,可以在肺组织中检测到不受控制的炎症。SARS-CoV-1E蛋白中的PDZ结合基序(PBM)已被证明是诱导细胞因子风暴的毒力因子。
方法:为了确定PBM诱导的基因表达波动,分析了感染野生型(SARS-CoV-1-E-wt)或重组病毒(SARS-CoV-1-E-mutPBM)的肺组织的微阵列测序数据,其次是功能富集分析。为了了解所筛选的基因在LUAD中的作用,计算总生存期和免疫相关性.
结果:共有12个基因可能通过表达变异和突变参与LUAD的初始和发育阶段。此外,共有12个基因失调可能导致预后较差.此外,PBM下调MAMDC2和ITGA8也可能影响患者预后.尽管保守的PBM(-D-L-L-V-)可以在冠状病毒的多个E蛋白的羧基末端发现,每种蛋白质的特定功能取决于整个氨基酸序列。
结论:总之,含有SARS-CoV-1E蛋白的PBM通过调节重要基因表达谱并随后影响免疫反应和总体预后来促进LUAD的致癌作用。
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