Heliyon (Mar 2024)

Integrated genomic and proteomic analyses identify PYGL as a novel experimental therapeutic target for clear cell renal cell carcinoma

  • Mingyong Li,
  • Guoqiang Zhu,
  • Yiqi Liu,
  • Xuefeng Li,
  • Yuxia Zhou,
  • Cheng Li,
  • Minglei Wang,
  • Jin Zhang,
  • Zhenping Wang,
  • Shuangfeng Tan,
  • Wenqi Chen,
  • Hu Zhang

Journal volume & issue
Vol. 10, no. 6
p. e28295

Abstract

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Sunitinib, the first-line targeted therapy for metastatic clear cell renal cell carcinoma (ccRCC), faces a significant challenge as most patients develop acquired resistance. Integrated genomic and proteomic analyses identified PYGL as a novel therapeutic target for ccRCC. PYGL knockdown inhibited cell proliferation, cloning capacity, migration, invasion, and tumorigenesis in ccRCC cell lines. PYGL expression was increased in sunitinib-resistant ccRCC cell lines, and CP-91149 targeting the PYGL could restore drug sensitivity in these cell lines. Moreover, chromatin immune-precipitation assays revealed that PYGL upregulation is induced by the transcription factor, hypoxia-inducible factor 1α. Overall, PYGL was identified as a novel diagnostic biomarker by combining genomic and proteomic approaches in ccRCC, and sunitinib resistance to ccRCC may be overcome by targeting PYGL.

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