Int J Med Sci 2022; 19(5):842-857. doi:10.7150/ijms.71703 This issue Cite

Research Paper

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

Yiting Wang1,3, Shuang Liu1, Shaoping Tian1, Runxuan Du2, Tianyu Lin1, Xuesong Xiao2, Rui Wang1, Ruibing Chen4, Hua Geng5,6, Saravanan Subramanian5,6, Yuanjie Niu2, Yong Wang2✉, Dan Yue1✉

1. Department of Microbiology, School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China
2. The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin Medical University, Tianjin 300211, China
3. Department of Clinical Laboratory, Tianjin Children's Hospital/Tianjin University Children's Hospital, Tianjin 300134, China
4. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
5. Center for Intestinal and Liver Inflammation Research, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
6. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

Citation:
Wang Y, Liu S, Tian S, Du R, Lin T, Xiao X, Wang R, Chen R, Geng H, Subramanian S, Niu Y, Wang Y, Yue D. C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation. Int J Med Sci 2022; 19(5):842-857. doi:10.7150/ijms.71703. https://www.medsci.org/v19p0842.htm
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Abstract

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Background: 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.

Methods: 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 in vitro. RNA stability assay was applied to characterize the mechanism of C1QBP regulating XDH transcription. In vivo, orthotopic tumor xenografts assay was performed to investigate the role of C1QBP in RCC progression.

Results: 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, C1QBP may affect XDH transcription by regulating the mRNA level of XDH transcriptional stimulators IL-6, TNF-α, and IFN-γ. 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.

Conclusion: C1QBP promotes the catabolism of hypoxanthine and elevates the apoptosis of RCC cells by modulating XDH-mediated ROS generation.

Keywords: Apoptosis, C1QBP, ROS, Renal cell carcinoma, XDH


Citation styles

APA
Wang, Y., Liu, S., Tian, S., Du, R., Lin, T., Xiao, X., Wang, R., Chen, R., Geng, H., Subramanian, S., Niu, Y., Wang, Y., Yue, D. (2022). C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation. International Journal of Medical Sciences, 19(5), 842-857. https://doi.org/10.7150/ijms.71703.

ACS
Wang, Y.; Liu, S.; Tian, S.; Du, R.; Lin, T.; Xiao, X.; Wang, R.; Chen, R.; Geng, H.; Subramanian, S.; Niu, Y.; Wang, Y.; Yue, D. C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation. Int. J. Med. Sci. 2022, 19 (5), 842-857. DOI: 10.7150/ijms.71703.

NLM
Wang Y, Liu S, Tian S, Du R, Lin T, Xiao X, Wang R, Chen R, Geng H, Subramanian S, Niu Y, Wang Y, Yue D. C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation. Int J Med Sci 2022; 19(5):842-857. doi:10.7150/ijms.71703. https://www.medsci.org/v19p0842.htm

CSE
Wang Y, Liu S, Tian S, Du R, Lin T, Xiao X, Wang R, Chen R, Geng H, Subramanian S, Niu Y, Wang Y, Yue D. 2022. C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation. Int J Med Sci. 19(5):842-857.

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