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
Affiliations
Mingyong Li
The First Affiliated Hospital, Department of Urology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Guoqiang Zhu
The First Affiliated Hospital, Department of Urology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Yiqi Liu
The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Xuefeng Li
The First Affiliated Hospital, Department of Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Yuxia Zhou
The First Affiliated Hospital, Department of Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Cheng Li
The First Affiliated Hospital, Department of Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Minglei Wang
Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China
Jin Zhang
Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, China
Zhenping Wang
The First Affiliated Hospital, Department of Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Shuangfeng Tan
The First Affiliated Hospital, Department of Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Wenqi Chen
Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, University of South China, 421000 Hengyang, Hunan, China; Corresponding author. Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, University of South China, 421000, Hengyang, Hunan, China.
Hu Zhang
The First Affiliated Hospital, Department of Urology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China; Corresponding author. The First Affiliated Hospital, Department of Urology, Hengyang Medical School, University of South China, 69 Chuanshan Road, Shigu District, Hengyang, Hunan, 421001, China.
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.
