The Study On Function And Functional Mechanism Of MCPIP1 In Cervical Cancer

According to the latest global cancer statistics,cervical cancer is the fourth most common malignancy in women worldwide.More than 600,000 new cases of cervical cancer and 340,000 deaths from cervical cancer in 2020,and the number is increasing every year.Currently,the treatment of cervical cancer is still dominated by hysterectomy,radiotherapy,and chemotherapy,but the overall prognosis is still unsatisfactory for patients with metastatic or recurrent disease.Therefore,in-depth study of the pathogenesis of cervical cancer and search for critical molecular targets are of great significance for the diagnosis and treatment of cervical cancer.MCPIP1,a well-studied member of the MCPIP protein family,can degrade various RNAs through its endoribonuclease activity.MCPIP1 plays a vital role in regulating inflammatory response,cell proliferation,apoptosis,angiogenesis,etc.Studies have shown that MCPIP1 is low expressed in various tumor tissues and cell lines,and the low expression of MCPIP1 can inhibit malignant tumor phenotypes by regulating cell cycle,cell invasion and migration,and angiogenesis.However,it remains unknown how MCPIP1 functions in cervical cancer.To explore the biological function of MCPIP1 in cervical cancer,we first constructed an inducible expression plasmid of MCPIP1.Our experiment results showed that MCPIP1 could inhibit the proliferation and migration of cervical cancer cells but promote apoptosis.Therefore,MCPIP1 may function as a tumor suppressor in cervical cancer.To clarify the molecular mechanism of the pro-apoptotic effect of MCPIP1 in cervical cancer cells,we firstly abolished the RNase activity of MCPIP1 through site-directed mutagenesis.Compared to wild-type MCPIP1,the MCPIP1 mutant D141 N without RNase activity could no longer inhibit the proliferation of cervical cancer cells nor promote apoptosis.Therefore,the pro-apoptotic effect of MCPIP1 in cervical cancer is dependent on its RNase activity.To identify the downstream effectors of MCPIP1 in cervical cancer,we focus the study on the IAP family members that degrade or restrain the activity of caspase-3.By q RT-PCR and Western Blot,we found that both the expression level of XIAP m RNA and protein is downregulated by MCPIP1,and the negative regulatory effect is dependent on MCPIP1’s RNase activity.Furthermore,we found that overexpression of XIAP can inhibit MCPIP1-induced cell apoptosis in MCPIP1 and XIAP coinfection experiments.In summary,we could that MCPIP1 can reduce the expression of XIAP and promote the activation of caspase-3,thereby promoting the apoptosis of cervical cancer cells.Based on the findings in our study,we revealed the molecular mechanism that MCPIP1 inhibits the expression of XIAP and promotes the apoptosis of cervical cancer cells.Our study may provide a theoretical reference for diagnosing and treatment of cervical cancer.