C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation

• Published in: International journal of medical sciences 2022-01, Vol.19 (5), p.842-857
• Main Authors: Wang, Yiting, Liu, Shuang, Tian, Shaoping, Du, Runxuan, Lin, Tianyu, Xiao, Xuesong, Wang, Rui, Chen, Ruibing, Geng, Hua, Subramanian, Saravanan, Niu, Yuanjie, Wang, Yong, Yue, Dan
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - genetics; Cancer therapies; Carcinoma, Renal Cell - pathology; Carrier Proteins - metabolism; Cold; Dehydrogenases; Humans; Hypoxanthines; Kidney cancer; Kidney Neoplasms - pathology; Metabolism; Metabolites; Metastasis; Mitochondrial Proteins - genetics; Patients; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Research Paper; RNA, Messenger; Xanthine Dehydrogenase - genetics; Xanthine Dehydrogenase - metabolism
• ISSN: 1449-1907
• DOI: 10.7150/ijms.71703

Complement component 1 Q subcomponent binding protein (C1QBP) plays a vital role in the progression and metabolism of cancer. Studies have shown that xanthine dehydrogenase (XDH)-derived reactive oxygen species (ROS) accelerates tumor growth, and also induces mutations or produces cytotoxic effects concurrently. However, the role of C1QBP in metabolism, oxidative stress, and apoptosis of renal cell carcinoma (RCC) cells have not yet been explored. Metabolomics assay was applied to investigate the role of C1QBP in RCC metabolism. C1QBP knockdown and overexpression cells were established via lentiviral infection and subjected to apoptosis and ROS assay . RNA stability assay was applied to characterize the mechanism of regulating transcription. , orthotopic tumor xenografts assay was performed to investigate the role of C1QBP in RCC progression. Metabolomics investigation revealed that C1QBP dramatically diminished the hypoxanthine content in RCC cells. C1QBP promoted the mRNA and protein expression of hypoxanthine catabolic enzyme XDH. Meanwhile, may affect transcription by regulating the mRNA level of transcriptional stimulators , , and . Moreover, the expression of C1QBP and XDH was lower in RCC tumors compared with the tumor-associated normal tissues, and their down-regulation was associated with higher Fuhrman grade. C1QBP significantly increased ROS level, apoptosis, and the expression of apoptotic proteins such as cleaved caspase-3 and bax/bcl2 via regulating XDH. C1QBP promotes the catabolism of hypoxanthine and elevates the apoptosis of RCC cells by modulating XDH-mediated ROS generation.