Aging
Navigate
Submit an Article
Research Paper|Volume 16, Issue 3|pp 2679—2701

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

Shiue-Wei Lai1, Pei-Wei Weng2,3,4, Vijesh Kumar Yadav5, Narpati Wesa Pikatan5, Chi-Tai Yeh5,6, Ming-Shou Hsieh7,8, Chu-Lin Chou9,10,11,12
  • 1Division of Hematology/Oncology, Department of Internal Medicine, Tri-service General Hospital, National Defense Medical Center, Taipei, Taiwan
  • 2Department of Orthopaedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • 3Department of Orthopaedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
  • 4Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
  • 5Department of Medical Research, Taipei Medical University Shuang-Ho Hospital, Taipei, Taiwan
  • 6Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung, Taiwan
  • 7Department of Dentistry, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
  • 8School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan
  • 9Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • 10Taipei Medical University-Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
  • 11Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan
  • 12Division of Nephrology, Department of Internal Medicine, Hsin Kuo Min Hospital, Taipei Medical University, Taoyuan City, Taiwan
* Equal contribution
Received: May 23, 2023Accepted: November 30, 2023Published: February 1, 2024
https://doi.org/10.18632/aging.205504

Copyright: © 2024 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 treatment resistance. Our experiments demonstrated that increasing DBT expression significantly reduces RCC cell growth and spread, underscoring its potential as a therapeutic target. This research sheds new light on the role of CRGs in ccRCC and their impact on drug resistance.