Underlying mechanisms of novel cuproptosis-related dihydrolipoamide branched-chain transacylase E2 (DBT) signature in sunitinib-resistant clear-cell renal cell carcinoma

Shiue Wei Lai, Pei Wei Weng, Vijesh Kumar Yadav, Narpati Wesa Pikatan, Chi Tai Yeh, Ming Shou Hsieh, Chu Lin Chou

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Renal cell carcinoma (RCC) is the predominant form of malignant kidney cancer. Sunitinib, a primary treatment for advanced, inoperable, recurrent, or metastatic RCC, has shown effectiveness in some patients but is increasingly limited by drug resistance. Recently identified cuproptosis, a copper-ion-dependent form of programmed cell death, holds promise in combating cancer, particularly drug-resistant types. However, its effectiveness in treating drug resistant RCC remains to be determined. Exploring cuproptosis's regulatory mechanisms could enhance RCC treatment strategies. Our analysis of data from the GEO and TCGA databases showed that the cuproptosis-related gene DBT is markedly under expressed in RCC tissues, correlating with worse prognosis and disease progression. In our study, we investigated copper CRGs in ccRCC, noting substantial expression differences, particularly in advanced-stage tumors. We established a connection between CRG expression levels and patient survival, positioning CRGs as potential therapeutic targets for ccRCC. In drug resistant RCC cases, we found distinct expression patterns for DBT and GLS CRGs, linked to renal cell carcinomas, sunitinib, cuproptosis, drug resistance treatment resistance. Our experiments demonstrated that increasing DBT expression significantly reduces RCC cell growth and spread, underscoring its potential as a therapeutic target.

Original languageEnglish
Pages (from-to)2679-2698
Number of pages20
JournalAging
Volume16
Issue number3
DOIs
Publication statusPublished - 2024

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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