Bal Albayrak Merve Gülsen, Korak Tuğcan, Kasap Murat, Akpinar Gürler
Department of Medical Biology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkiye.
Turk J Med Sci. 2024 Aug 19;54(6):1369-1380. doi: 10.55730/1300-0144.5920. eCollection 2024.
BACKGROUND/AIM: Lung cancer, a predominant contributor to cancer mortality, is characterized by diverse etiological factors, including tobacco smoking and genetic susceptibilities. Despite advancements, particularly in nonsmall-cell lung cancer (NSCLC), therapeutic options for lung squamous cell carcinoma (LUSC) are limited. Transposable elements (TEs) and their regulatory proteins, such as tigger transposable element derived (TIGD) family proteins, have been implicated in cancer development. TIGD1, upregulated in various cancers, including LUSC, lacks a defined function. The aim of our study was to elucidate the biological functions, associated pathways, and interacting proteins of TIGD1.
The GSE229260 microarray dataset was investigated using the GEO2R tool to identify the differentially expressed genes (DEGs) in TIGD1 silenced in A549 lung cancer cells in contrast to controls. Enrichment analyses and protein-protein interaction (PPI) network construction were performed to uncover key pathways using KEGG and STRING analyses. Hub genes were determined through the intersection of DEGs with lung cancer-related genes via Cytoscape software and the cytoHubba plug-in, and their functions were analyzed. Immune and stromal scores of hub genes were also evaluated using the ESTIMATE algorithm.
Analyzing microarray data from TIGD1-silenced A549 NSCLC cells, a total of 13 upregulated DEGs and 1 downregulated DEGs were identified. The TIGD1-associated DEGs revealed significant involvement in crucial molecular pathways, including the PI3K/AKT, FOXO, and p53 signaling pathways. The hub genes AKT1, BRAF, SRC, GAPDH, CCND1, CDKN2A, CTNNB1, KRAS, MYC, and TP53 emerged as central regulators of cell proliferation, apoptosis, and protein metabolism. The hub genes exhibited negative correlations with immune and stromal components in the tumor microenvironment, suggesting their potential as biomarkers for lung cancer therapy.
This study elucidates the potential functions of TIGD1 in lung cancer and identifies promising biomarker candidates associated with TIGD1 gene expression, presenting potential therapeutic targets for lung cancer therapies.
背景/目的：肺癌是导致癌症死亡的主要原因，其病因多种多样，包括吸烟和遗传易感性。尽管取得了进展，尤其是在非小细胞肺癌（NSCLC）方面，但肺鳞状细胞癌（LUSC）的治疗选择仍然有限。转座元件（TEs）及其调控蛋白，如源自触发转座元件（TIGD）家族的蛋白，与癌症发展有关。TIGD1在包括LUSC在内的多种癌症中上调，但其功能尚不明确。本研究的目的是阐明TIGD1的生物学功能、相关通路和相互作用蛋白。
使用GEO2R工具研究GSE229260芯片数据集，以鉴定与对照相比在A549肺癌细胞中沉默TIGD1后差异表达的基因（DEGs）。使用KEGG和STRING分析进行富集分析和蛋白质-蛋白质相互作用（PPI）网络构建，以揭示关键通路。通过Cytoscape软件和cytoHubba插件，通过将DEGs与肺癌相关基因相交来确定枢纽基因，并分析其功能。还使用ESTIMATE算法评估枢纽基因的免疫和基质评分。
分析来自沉默TIGD1的A549 NSCLC细胞的芯片数据，共鉴定出13个上调的DEGs和1个下调的DEGs。与TIGD1相关的DEGs显示出显著参与关键分子通路，包括PI3K/AKT、FOXO和p53信号通路。枢纽基因AKT1、BRAF、SRC、GAPDH、CCND1、CDKN2A、CTNNB1、KRAS、MYC和TP53成为细胞增殖、凋亡和蛋白质代谢的核心调节因子。枢纽基因与肿瘤微环境中的免疫和基质成分呈负相关，表明它们作为肺癌治疗生物标志物的潜力。
本研究阐明了TIGD1在肺癌中的潜在功能，并鉴定出与TIGD1基因表达相关的有前景的生物标志物候选物，为肺癌治疗提供了潜在的治疗靶点。
