Background:Cervical cancer is primarily associated with persistent infection by high-risk human papillomaviruses(HR-HPVs),whose oncoproteins modulate key cellular pathways involved in proliferation and apoptosis.Merke...Background:Cervical cancer is primarily associated with persistent infection by high-risk human papillomaviruses(HR-HPVs),whose oncoproteins modulate key cellular pathways involved in proliferation and apoptosis.Merkel cell polyomavirus(MCPyV)has also been detected in cervical tissues,and its small T(sT)protein shares functional similarities with HR-HPV oncoproteins,suggesting a potential role in tumorigenesis.Methods:This study investigated whether MCPyV sT reduces 5-fluorouracil(5-FU)-induced apoptosis and in-fluences HPV16 oncogene expression and proliferation in Ca Ski cells.The MCPyV sT gene was cloned into a mammalian expression vector,transfected into Ca Ski cells,and confirmed by western blotting.Cytotoxicity as-says assessed the effects of MCPyV sT on 5-FU-treated cells,while RT-qPCR quantified viral oncogene expression.Annexin V/PI flow cytometry and Ki-67 immunostaining were used to evaluate apoptosis and proliferation.Results:MCPyV sT expression enhanced cell viability,increased the IC50 of 5-FU,and significantly reduced 5-FU-induced apoptosis.It also markedly upregulated HPV E5 and E6/E7 mRNA levels(p<0.001)and promoted proliferation.The combined presence of MCPyV sT and HPV oncoproteins synergistically increased resistance to 5-FU-induced apoptosis,oncogene expression,and cell growth.Conclusions:These findings underscore the potential cooperative effects of viral oncoproteins from distinct viruses in driving therapeutic resistance,highlighting the need for further research into their molecular interactions to inform targeted cervical cancer treatments.展开更多
文摘Background:Cervical cancer is primarily associated with persistent infection by high-risk human papillomaviruses(HR-HPVs),whose oncoproteins modulate key cellular pathways involved in proliferation and apoptosis.Merkel cell polyomavirus(MCPyV)has also been detected in cervical tissues,and its small T(sT)protein shares functional similarities with HR-HPV oncoproteins,suggesting a potential role in tumorigenesis.Methods:This study investigated whether MCPyV sT reduces 5-fluorouracil(5-FU)-induced apoptosis and in-fluences HPV16 oncogene expression and proliferation in Ca Ski cells.The MCPyV sT gene was cloned into a mammalian expression vector,transfected into Ca Ski cells,and confirmed by western blotting.Cytotoxicity as-says assessed the effects of MCPyV sT on 5-FU-treated cells,while RT-qPCR quantified viral oncogene expression.Annexin V/PI flow cytometry and Ki-67 immunostaining were used to evaluate apoptosis and proliferation.Results:MCPyV sT expression enhanced cell viability,increased the IC50 of 5-FU,and significantly reduced 5-FU-induced apoptosis.It also markedly upregulated HPV E5 and E6/E7 mRNA levels(p<0.001)and promoted proliferation.The combined presence of MCPyV sT and HPV oncoproteins synergistically increased resistance to 5-FU-induced apoptosis,oncogene expression,and cell growth.Conclusions:These findings underscore the potential cooperative effects of viral oncoproteins from distinct viruses in driving therapeutic resistance,highlighting the need for further research into their molecular interactions to inform targeted cervical cancer treatments.
