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

Abstract

Background Clear cell renal cell carcinoma (ccRCC) is 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 noncoding 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 burdens 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. The essential genes FDX1 and DLST of cuproptosis were detected by western blot. 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 a significant difference in tumor mutation burden between the groups, which 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 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 that the proliferation and migration of t ACHN cells in the LINC02154 knockdown group were inhibited. The western blot results showed that the knockdown of LINC02154 significantly affected the expression of FDX1 and DLST, critical genes of cuproptosis. Conclusion Finally, we demonstrated that LINC02154 and our constructed risk signature could predict outcomes and have potential clinical value.

Bioinformatics analysis and experimental validation of m6A and cuproptosis-related lncRNA NFE4 in clear cell renal cell carcinoma

“…constructed a five-lncRNA risk model based on cuproptosis- and m6A-related lncRNAs [ 57 ]. In KIRC, LINC02154 is identified to be a cuproptosis-linked gene [ 47 ]. However, here, it was found that NFE4 was a novel cuproptosis- and m6A-related lncRNA.…”

Identification of a new gene signature for prognostic evaluation in cervical cancer: based on cuproptosis-associated angiogenesis and multi-omics analysis

“…For example, pazopanib has improved PFS and OS in patients with advanced or recurrent cervical cancer, while AMG.706 (motesanib) inhibits angiogenesis in recurrent ovarian cancer and CEP.701 (lestaurtinib) inhibits the growth of cervical cancer cells [ 60 – 62 ]. Studies have shown differences in IC50 values of drugs such as pazopanib, sorafenib, sunitinib, and imatinib among different CuRA subgroups of clear cell renal cell carcinoma, bladder cancer, and triple-negative breast cancer [ 63 – 65 ]. Our study also suggested that in the high CuRA score group, IC50 values of PARP inhibitors ABT.888 (Veliparib), AZD.2281 (Olaparib), and MS.275 (Entinostat) were higher, indicating that these drugs were effective bythe cuproptosis-dependent angiogenesis pathway These studies supported our results of drug sensitivity analysis and suggested that research on anti-cuproptosis-related angiogenesis targeted drugs may bring new treatment ideas and expand the application of drugs in the current dilemma.…”

CD276 enhances sunitinib resistance in clear cell renal cell carcinoma by promoting DNA damage repair and activation of FAK-MAPK signaling pathway

“…ALP and ALBI are widely utilized markers in diverse medical settings. Elevated ALP levels can serve as an indication of bone metastasis in cancer patients, including ccRCC, which is potentially associated with the role of CD276 in cancer progression and metastatic potential [ 40 ]. These findings highlight its potential as a target for cancer immunotherapy [ 41 ].…”