Bioinformatics analysis and experimental validation of cuproptosis- related lncRNA LINC02154 in clear cell renal cell carcinoma

Abstract

Abstract Background Clear cell renal cell carcinoma (ccRCC) is very common in urinary system tumors. Cuproptosis is a non-apoptotic cell death pathway. Copper binds to fatty acylated mitochondrial proteins and activates various forms of cell death. LncRNA LINC02154 is significantly highly expressed in cells and tissues of many types of tumors, and the risk signature of LINC02154 in some tumors has been validated for effectiveness. Methods We constructed a risk prognostic signature by obtaining differentially expressed long non-coding RNAs (lncRNAs) associated with ccRCC outcomes and cuproptosis from The Cancer Genome Atlas (TCGA). We used TCGA to construct training and testing sets to analyze the risk signature and the impact of LINC02154, and we performed relevant survival analyses. Tumor mutational burden were analyzed in different LINC02154 expression groups and risk score groups. We next analyzed the immune microenvironment of LINC20154. We performed LINC20154-related drug sensitivity analyses. We also investigated the cellular function of LINC02154 in the ACHN cell line and performed CCK-8 assay, EdU, wound-healing assay, and Transwell assay Results We demonstrated that LINC02154’s impact on outcomes was statistically significant. We also demonstrated the association of different ages, genders, stages, and grades with LINC02154 and risk models. The results showed that there was a significant difference in tumor mutation burden between the groups, and this difference was closely related to clinical prognosis. We found differences in immune cells among groups with different levels of LINC02154 expression and significant differences in immune function, immunotherapeutic positive markers, and critical steps of the immune cycle. The sensitivity analysis was showed that differential expression of LINC02154 discriminated between sensitivity to axitinib, doxorubicin, gemcitabine, pazopanib, sorafenib, sunitinib, and temsirolimus. This difference was also present in the high risk group and low risk group. We demonstrated the proliferation and migration of t ACHN cells in the LINC02154 knockdown group were inhibited. Conclusion Finally, we demonstrated that LINC02154 and our constructed risk signature can predict outcomes and have potential clinical value.