Identify CTBP1-DT as an immunological biomarker that promotes lipid synthesis and apoptosis resistance in KIRC

• Published in: Gene Vol. 914; p. 148403
• Main Authors: Li, Haolin, Fei, Mintian, Zhang, Yi, Xu, Qili, Feng, Rui, Cao, Jing, Qu, Yan, Xiao, Haibing
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2024
• Subjects: Apoptosis; CTBP1-DT; KIRC; Lipid; lncRNA; Tumor Microenvironment; lncRNAs; HOTAIR; lncRNA; CDCA3; Tumor Microenvironment; IPS; PFS; RT-qPCR; CEP55; MSI; OS; USP22; ASOs; TMB; GO; GSEA; KIRC; Lipid; TCGA; MMP11; CTBP1-DT; RCC; SNHG12; ZNF217; Apoptosis
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2024.148403

•CTBP1-DT is a lncRNA located in the nucleus that is significantly upregulated in clear cell renal cell carcinoma.•Downregulate CTBP1-DT could inhibit cell lipid content.•CTBP1-DT is linked with immune cell infiltration in clear cell renal cell carcinoma, especially macrophages. 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.