关键词: Apoptosis CTBP1-DT KIRC Lipid Tumor Microenvironment lncRNA

Mesh : Humans Apoptosis Alcohol Oxidoreductases / genetics metabolism Biomarkers, Tumor / genetics metabolism Cell Line, Tumor DNA-Binding Proteins / genetics metabolism Cell Proliferation Carcinoma, Renal Cell / genetics pathology metabolism immunology Kidney Neoplasms / genetics pathology immunology metabolism Cell Movement Gene Expression Regulation, Neoplastic RNA, Long Noncoding / genetics Lipids Prognosis Male Female

来  源:   DOI:10.1016/j.gene.2024.148403

Abstract:
Recently, mounting evidence has highlighted the essential function of the C-terminal binding protein-1 divergent transcript (CTBP1-DT) in malignancies. However, its role in kidney renal clear cell carcinoma (KIRC) remains largely unknown. Our study aimed to identify the potential function of CTBP1-DT in KIRC. RT-qPCR, Kaplan-Meier survival analysis, Cox regression analysis, and nomogram analysis were utilized to determine the expression and effects of CTBP1-DT on survival. The subcellular localization of CTBP1-DT was determined using RNA fluorescence in situ hybridization (FISH). To investigate the functions of CTBP1-DT in regulating KIRC cell proliferation, migration, invasion, lipid synthesis, and apoptosis, we conducted CCK8, EdU, Transwell, and Oil Red O staining and cell apoptosis staining assays. The relationships between CTBP1-DT and the tumor microenvironment were investigated with multiple bioinformatics analysis algorithms and databases, including CYBERSORT, TIMER2, Spearman correlation test, tumor mutation burden (TMB), microsatellite instability (MSI), and immunophenoscore (IPS). According to our results, CTBP1-DT is a lncRNA located in the nucleus that is significantly upregulated in KIRC and is correlated with better clinical outcomes. Downregulating CTBP1-DT inhibited cell viability, migration, invasion, and lipid synthesis but triggered cell apoptosis. Additionally, we explored the potential effect of CTBP1-DT in regulating immune cell infiltration in KIRC and other malignancies. Furthermore, CTBP1-DT could be used to predict the effectiveness of targeted drugs and immune checkpoint inhibitors. In conclusion, we identified CTBP1-DT as a potential immunological biomarker and discovered the potential role of CTBP1-DT in regulating lipid synthesis and apoptosis resistance.
摘要:
最近,越来越多的证据强调了C端结合蛋白-1发散转录本(CTBP1-DT)在恶性肿瘤中的基本功能。然而,其在肾肾透明细胞癌(KIRC)中的作用尚不清楚.我们的研究目的是确定CTBP1-DT在KIRC中的潜在功能。RT-qPCR,Kaplan-Meier生存分析,Cox回归分析,和列线图分析用于确定CTBP1-DT的表达和对生存的影响。使用RNA荧光原位杂交(FISH)确定CTBP1-DT的亚细胞定位。探讨CTBP1-DT对KIRC细胞增殖的调控作用,迁移,入侵,脂质合成,和细胞凋亡,我们进行了CCK8EdU,Transwell,和油红O染色和细胞凋亡染色测定。利用多种生物信息学分析算法和数据库研究CTBP1-DT与肿瘤微环境的关系,包括CYBERSORT,TIMER2,Spearman相关检验,肿瘤突变负荷(TMB),微卫星不稳定性(MSI),和免疫表型(IPS)。根据我们的结果,CTBP1-DT是位于细胞核中的lncRNA,其在KIRC中显著上调并且与更好的临床结果相关。下调CTBP1-DT抑制细胞活力,迁移,入侵,和脂质合成,但引发细胞凋亡。此外,我们探讨了CTBP1-DT在KIRC和其他恶性肿瘤中调节免疫细胞浸润的潜在作用。此外,CTBP1-DT可用于预测靶向药物和免疫检查点抑制剂的有效性。总之,我们将CTBP1-DT鉴定为潜在的免疫学生物标志物,并发现CTBP1-DT在调节脂质合成和抗凋亡中的潜在作用.
公众号