Luciferase Reporter Cell Line - ACHN

Complement component 1 Q subcomponent-binding protein (C1QBP) plays a pivotal role in cancer progression and metabolic processes. Studies have demonstrated that reactive oxygen species (ROS) derived from xanthine dehydrogenase (XDH) not only accelerate tumor growth but also induce gene mutations or exert cytotoxic effects. However, the specific role of C1QBP in the metabolism, oxidative stress, and apoptosis of renal cell carcinoma (RCC) cells remains unexplored. Here, metabolomic analyses reveal that C1QBP significantly reduces intracellular hypoxanthine levels in RCC cells. C1QBP promotes the mRNA and protein expression of XDH-the enzyme responsible for hypoxanthine catabolism. Concurrently, C1QBP may influence the transcriptional process of XDH by modulating the mRNA levels of XDH transcriptional activators, such as IL-6, TNF-α, and IFN-γ. Furthermore, compared to adjacent normal tissues, RCC tumor tissues exhibit lower expression levels of both C1QBP and XDH; notably, the downregulation of these two proteins correlates positively with higher Fuhrman grades. By regulating XDH, C1QBP significantly elevates ROS levels and apoptotic rates, while also upregulating the expression of apoptosis-related proteins, including cleaved Caspase-3 and the Bax/Bcl-2 ratio.

To elucidate the role of C1QBP in the in vivo progression of renal cell carcinoma (RCC), researchers constructed an orthotopic tumor xenograft model with implantation of stable C1QBP overexpression and control ACHN cells with luciferase into the left kidney capsule of BALB/c nude mice. Eight weeks later, the mice were administered an intraperitoneal injection of luciferin, and in vivo imaging was performed to assess the bioluminescence intensity of the primary tumors. The results demonstrated that, compared to the control group, the mice in the C1QBP-overexpression group exhibited lower bioluminescence intensity (Figure 1A, B). Subsequently, the researchers harvested the primary tumors from both groups of mice; the results revealed that the tumor weight in the C1QBP-overexpression group was significantly lower (Figure 1C), suggesting that C1QBP plays a pivotal role in the in vivo growth of RCC tumors. Furthermore, they conducted immunohistochemical (IHC) staining analysis on tissue sections of the primary renal tumors. The results indicated that the expression level of XDH was upregulated in the C1QBP-overexpression group (Figure 1D), suggesting that C1QBP is capable of enhancing XDH expression. Additionally, in the C1QBP-overexpression group, the researchers detected an upregulation in the expression of Caspase-3 and Bax, while the expression of Bcl-2 was downregulated (Figure 1D). Collectively, these data indicate that C1QBP participates in the regulation of RCC tumor growth in vivo.

Figure 1. C1QBP suppresses RCC tumor growth and regulates the expression of XDH and apoptotic proteins in vivo. (Wang, Yiting, et al., 2022)