MCPIP1 Promotes Cell Proliferation,Migration,and Angiogenesis Of Glioma By Regulating VEGFA/ERK Pathway

Gliomas are statistically very common tumors of extremely high malignancy in recent years and are primary intracranial tumors,accounting for 75% of all primary malignant brain tumors in adults,and have a poor five-year prognosis.The main clinical treatment for glioma today is surgical resection followed by radiation and chemotherapy.A growing number of studies have shown that glioma development is associated with abundant angiogenesis.However,little is known about how angiogenesis is regulated during the development of glioma.In this study,we found that MCPIP1,which is highly expressed in glioma,promotes angiogenesis through VEGFA/ERK-mediated signaling pathway,providing some clues to the molecular mechanism of angiogenesis during glioma development.Firstly,we obtained glioma patient data through databases CGGA and GAPIE,and correlated the expression of MCPIP1 with the survival rate of glioma patients,,and the results showed that MCPIP1 was negatively correlated with the survival rate of patients,and then we used western blot,histochemistry and PCR techniques to detect MCPIP1 in glioma patient tissues and glioma cell lines mRNA expression,and the results showed that the pathological content of MCPIP1 was higher than that of normal brain tissue,and the expression of MCPIP1 in tumor cells was higher than that of the control group,and the above experimental results indicated that MCPIP1 might inhibit glioma cell growth.;To further verify this,we purchased MCPIP1 knockdown lentivirus infected glioma cell lines U87 MG and U251 MG and screened stable transgenic strains by CCK-8,EDU staining,cell scratch assay,Transwell invasion and migration,and we found that MCPIP1 downregulation inhibited the proliferation,invasion and migration of glioma cells.Since further development of glioma is associated with angiogenesis and VEGFA promotes angiogenesis,we first analyzed the correlation between MCPIP1 expression and VEGFA in the database of glioma patients,and the results showed that MCPIP1 was positively correlated with VEGFA expression,and next we further verified by tubule formation and Western blot experiments,and the results showed that MCPIP1 can upregulate the expression of VEGFA in glioma and promote the secretion of VEGFA to the periphery.The above experimental results indicate that glioma MCPIP1 affects angiogenesis by regulating the expression of VEGFA.Mechanistically,we found that VEGFA stimulates angiogenesis through ERK pathway.Finally,the results of subcutaneous tumorigenesis experiments in nude mice showed that the tumor growth volume was significantly reduced after MCPIP1 knockdown,and the expression levels of VEGFA and CD34 were significantly decreased,and blocking the expression and secretion of VEGFA could inhibit angiogenesis in the MCPIP1-mediated xenograft model.The results of the above in vivo tumorigenic experiments in mice showed that the knockdown of MCPIP1 resulted in smaller tumor growth volume and reduced angiogenesis.In this study,we found that overexpression of MCPIP1 in glioma cells is a promoter of glioma angiogenesis.Furthermore,the above results demonstrate that MCPIP1 regulation of the VEGFA/ERK pathway plays an integral role in angiogenesis and glioma progression,suggesting that targeting MCPIP1 may be a potential selective therapeutic strategy for glioma.