Human cytomegalovirus UL82 promotes colorectal cancer cell proliferation through inhibiting the ubiquitination of OGDH via ANGPT2

Abstract

Human cytomegalovirus (HCMV) infection and its association with tumorigenesis and tumor progression have garnered increasing attention. Previous research results have indicated that the detection rate of HCMV UL82 is higher in colorectal cancer (CRC) tissues and is correlated with poor prognosis in patients, yet the underlying mechanisms remain unclear. In this study, a cell model transfected with UL82 was established. Through in vitro and in vivo experiments, it was found that UL82 promoted the proliferation of CRC cells. Transcriptomic and metabolomic analyses revealed that UL82 could influence CRC glucose metabolism and cell proliferation by upregulating the key TCA cycle enzyme OGDH. Additionally, UL82 also affected CRC cell proliferation by upregulating the expression of ANGPT2, and silencing ANGPT2 resulted in a reduction in OGDH protein levels. Finally, through the investigation of the ubiquitin-mediated degradation pathway of OGDH, it was demonstrated that ANGPT2 inhibited the protein degradation of OGDH via deubiquitination, thereby maintaining its stability. In summary, UL82 promotes CRC cell proliferation by upregulating ANGPT2, which inhibits the ubiquitin-mediated degradation of OGDH, suggesting that targeting the UL82/ANGPT2/OGDH axis may offer a potential clinical strategy for the diagnosis of CRC.