Li Mingyong, Zhu Guoqiang, Liu Yiqi, Li Xuefeng, Zhou Yuxia, Li Cheng, Wang Minglei, Zhang Jin, Wang Zhenping, Tan Shuangfeng, Chen Wenqi, Zhang Hu
The First Affiliated Hospital, Department of Urology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
Heliyon. 2024 Mar 16;10(6):e28295. doi: 10.1016/j.heliyon.2024.e28295. eCollection 2024 Mar 30.
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.
舒尼替尼是转移性透明细胞肾细胞癌（ccRCC）的一线靶向治疗药物，但由于大多数患者会产生获得性耐药，因此面临着重大挑战。综合基因组和蛋白质组分析确定PYGL是ccRCC的一个新的治疗靶点。敲低PYGL可抑制ccRCC细胞系的细胞增殖、克隆能力、迁移、侵袭和肿瘤发生。在对舒尼替尼耐药的ccRCC细胞系中，PYGL表达增加，而靶向PYGL的CP-91149可恢复这些细胞系的药物敏感性。此外，染色质免疫沉淀试验表明，转录因子缺氧诱导因子1α可诱导PYGL上调。总体而言，通过在ccRCC中结合基因组和蛋白质组方法，确定PYGL为一种新的诊断生物标志物，靶向PYGL可能克服ccRCC对舒尼替尼的耐药性。
