SND1作为肺腺癌癌基因和预后标志物的鉴定与分析

Identification and Analysis of SND1 as an Oncogene and Prognostic Biomarker for Lung Adenocarcinoma

背景与目的 转录因子(transcription factor,TF)可以结合特异性序列,对下游基因起到促进或抑制的作用,对肿瘤的发生、迁移、侵袭等生物学过程都有重要的影响。葡萄球菌含核酸酶结构域l(Staphylococcal nuclease-containing structural domain 1,SND1)作为一种转录共激活因子,被认为是肿瘤治疗的一个潜在靶点。然而,其在肺腺癌(lung adenocarcinoma,LUAD)中的表达及作用尚不清楚。本研究主要探索SND1作为LUAD癌基因在LUAD中的作用。方法 从癌症基因组图谱(The Cancer Genome Atlas,TCGA)、基因表达综合数据库(Gene Expression Omnibus,GEO)、临床蛋白质组肿瘤分析联盟(Clinical Proteomic Tumor Analysis Consortium,CPTAC)和人类蛋白图库(Human Protein Atlas,HPA)等数据库获取数据,探讨SND1表达与LUAD患者预后、免疫细胞浸润和亚细胞定位的关系;利用EdU法、CCK-8法、流式细胞术、细胞划痕实验、Transwell实验、蛋白印迹实验等体外实验探讨SND1在LUAD中的功能作用。结果 在LUAD中SND1的表达上调,且与患者预后不良有关。SND1主要存在于LUAD细胞的细胞质中。富集分析表明SND1与细胞周期密切相关,包括DNA复制和染色体分离等。免疫细胞浸润分析显示,SND1与多种免疫细胞群有关,包括T细胞、B细胞、细胞毒性细胞和树突状细胞。体外研究表明沉默SND1可抑制LUAD细胞的增殖、侵袭和迁移,下调SND1可阻断G1期细胞周期进程。结论 SND1可能是LUAD重要的预后生物标志物,其可促进LUAD细胞的增殖和迁移。

Background and objective Transcription factor(TF)can bind specific sequences that either promotes or represses the transcription of target genes,and exerts important effects on tumorigenesis,migration,invasion.Staphylococcal nuclease-containing structural domain 1(SND1),which is a transcriptional co-activator,is considered as a promising target for tumor therapy.However,its role in lung adenocarcinoma(LUAD)remains unclear.This study aims to explore the role of SND1 in LUAD.Methods Data from The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),Clinical Proteomic Tumor Analysis Consortium(CPTAC),and Human Protein Atlas(HPA)database was obtained to explore the association between SND1 and the prognosis,as well as the immune cell infiltration,and subcellular localization in LUAD tissues.Furthermore,the functional role of SND1 in LUAD was verified in vitro.EdU assay,CCK-8 assay,flow cytometry,scratch assay,Transwell assay and Western blot were performed. Results SND1 was found to be upregulated and high expression of SND1is correlated with poor prognosis of LUAD patients. In addition, SND1 was predominantly present in the cytoplasm of LUAD cells. Enrichment analysis showed that SND1 was closely associated with the cell cycle, as well as DNA replication, and chromosome segregation. Immune infiltration analysis showed that SND1 was closely associated with various immune cell populations, including T cells, B cells, cytotoxic cells and dendritic cells. In vitro studies demonstrated that silencing of SND1 inhibited cell proliferation, invasion and migration of LUAD cells. Besides, cell cycle was blocked at G1 phase by down-regulating SND1. Conclusion SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.