The Expression And Significance Of MSI2 In Glioma

Objective:Glioma originate from a primary malignancy of the neuroepithelium.In the intracranial central nervous system,the incidence of this tumor is as high as 40%.Glioblastoma is characterized by abnormal proliferation,invasiveness,anti-apoptosis,invasive growth,etc.Therefore,surgical resection is difficult and prognosis is poor.Although there have been improvements in glioblastoma surgery,chemotherapy,and radiotherapy,its efficacy has not been significantly improved.In spite of adopting comprehensive treatment methods in recent years(surgery full cut + conformal split radiotherapy + temozolomide chemotherapy),the survival time of patients with glioblastoma(WHO IV)is still less than 15 months,so looking for effective against the glial cells The specific molecular sites of tumors increase the prognosis of glioma patients,which is highly favored by researchers.As an evolutionarily conserved RNA-binding protein,MSI2 activates Wnt signaling by inhibiting DKK1 expression,thereby ensuring that cytosolic ?-catenin levels are not degraded,and accumulation of excess ?-catenin translocates into nuclear TCF/LEF transcription Factor binding activates the transcriptional activity of target genes such as c-myc and cyclinD1,which affects cell growth,differentiation,and migration,eventually leading to tumorigenesis.MSI2 is highly expressed in various solid tumors(including liver cancer,colon adenocarcinoma,uveal melanoma,gastric cancer,bladder cancer,lung cancer,pancreatic cancer)and promotes the progression of solid tumors.However,as of now,the relationship between the MSI2 gene and glioma has not been reported in the literature.This article aims to explore the expression of MSI2 in glioma and its correlation with this tumor.The Wnt/?-catenin signaling pathway is evolutionarily conserved in organisms and plays a key role in the development of neural stem cells and embryos.Because the key proteins of this pathway are mainly encoded by important oncogenes and tumor suppressor genes,the abnormal activation of this pathway plays an important role in the formation and progression of tumors.Studies have shown that inappropriate activation of the Wnt/?-catenin signaling pathway contributes to the progression of glioma.Methods:In this experiment,Western blot was used to detect the expression of MSI2 protein in glioma cell lines(U373,U87 and U251).The RT-PCR method was used to verify whether the MSI2 mRNA expression in three cell lines(U373,U87 and U251)was consistent with the MSI2 protein expression level.The expression of MSI2 in 68 cases of brain glioma and 6 cases of normal brain tissue was detected by immunohistochemistry.The correlation between the expression of this protein and the pathological grade of the tumor was also studied.Results:(1)Western blot analysis showed that MSI2 protein was more highly expressed in U251 cell line than other two cell lines(U373,U87).(2)RT-PCR showed that the expression of MSI2 mRNA was higher in U251 cell lines than in the other two cell lines(U373,U87),and the consistency between RT-PCR and Western blot was consistent.(3)The results of immunohistochemistry showed that:(1)MSI2 is not expressed in normal brain tissue and is commonly overexpressed in gliomas.(2)With the increase of malignant degree and pathological grade of glioma,the expression level of MSI2 protein also increased,and its expression level was positively correlated with the malignant grade of the tumor.Conclusion:Studies have shown that MSI2 is expressed in glioma cell lines and its results are consistent with RT-PCR and Western blot results.MSI2 protein is commonly expressed in glioma tissues,and its expression level is positively correlated with the pathological grade of the tumor.This suggests that MSI2 is closely related to the formation and progression of gliomas.Therefore,molecular targeting MSI2 gene may provide a theoretical basis and thinking for the treatment of glioma disease.