Background: Merkel Cell Polyomavirus (MCPvV) is the primary cause of Merkel Cell Carcinoma (MCC), a rare yet highly aggressive type of skin cancer. Tumour suppressor gene INPP4B is significantly downregulated in MCC and other cancers, subsequently, this activates the PI3K/Akt/mTOR signalling pathway, which ultimately leads to uncontrolled cellular proliferation. In this study, we assessed the effect of MCV early region on INPP4B expression and cellular proliferation. We hypothesize that the large T-Antigen (LT) or truncated Large T-antigen (∆LT) of the MCV early region downregulates INPP4B expression, thus inducing cell proliferation.
Methods: The pLXSN constructs containing either MCPyV full length early region (FL), LT or ∆LT, were transfected into HEK-293, HeLaT cells and primary fibroblasts. The changes in INPP4B expression after transfection were assessed using qPCR.
Result: Transfection of FL, LT or ∆LT in HEK293 and HeLa cells significantly downregulated INPP4B expression. In contrast, the expression of INPP4B expression was upregulated in fibroblasts transfected with FL or LT, and no changes were observed in primary fibroblasts transfected with ∆LT.
Conclusion: The difference in INPP4B expression between the cell lines indicate that INPP4B is already dysregulated in transformed cells. The upregulation of INPP4B expression in primary cells represents natural infection. The absence of INPP4B upregulation in ∆LT suggests that the presence of C-terminus of the MCV early region, which is truncated in ∆LT through truncation, is important in the regulation of INPP4B expression.