Role And Mechanism Of STC1 In The Survival And Stemness Maintenance Of Glioma Cells

The incidence of brain tumors is very young,and the main malignant brain tumors are gliomas.According to the degree of malignancy of gliomas,it can be divided into four grades from Ⅰ to Ⅳ,among which grade Ⅳ is the highest degree of malignancy.Glioblastoma(GBM)belongs to grade Ⅳ glioma with high degree of malignancy,and the tumor cells are differentiated.The degree is low,the patient’s prognosis is poor,the median survival time is only about 14 months,and the fate of relapse is hard to escape after treatment.Although a variety of new treatment methods have been developed for cancer,such as immunotherapy,nano-delivery technology,etc.,the special location of glioma and the existence of the blood-brain barrier(BBB)limit the application of many therapie.Cancer Stem Cell(CSC)is a special group of tumors with similar characteristics of stem cells.It plays an important role in tumor occurrence,resistance to treatment,and recurrence.Such cells have been isolated from many solid tumors such as glioma,breast cancer,colorectal cancer.Therefore,targeted therapy for CSC based on the characteristics of CSC is expected to slow down the rate of malignant tumor progression and improve the prognosis of patients.In this study,a three-dimensional soft fibrin gel system was constructed using fibrinogen and thrombin,and this system was used to enrich glioma stem cells(GSC)from the glioblastoma(GBM)cell line DBTRG-05 MG,and the stemness of the enriched GSCs was verified.In order to explore the difference between GSC and GBM cells,we performed transcriptome sequencing and biometric analysis on the these two different population of cells,screened out genes that are differentially expressed in GSC and GBM cells,and selected STC1 as the target gene for in-depth study.We have obtained the following results:1.The cells enriched by the three-dimensional soft fibrin gel system have stronger stemness,such as high expression of GSC markers,stronger tolerance to Temozolomide(TMZ),and stronger in vivo tumorigenic ability.2.We analyzed the expression of GSC and common glioma cells at the transcription level,performed the enrichment analysis for significantly differentially expressed genes,and obtained some pathways that may play an important role in GSC.3.STC1 is highly expressed in GBM samples from patients,and the expression level of STC1 in GSC is higher than that of ordinary glioma cells.4.Overexpression of STC1 can increase the expression of some GSC markers of the glioma cell lines DBTRG-05 MG,U-87 MG,U251,increase the ability to form spheroids and the resistance to TMZ.Knockdown of STC1 will reduce the expression of some GSC markers in the glioma cell lines DBTRG-05 MG and U-87 MG,and increase the sensitivity to TMZ.5.Overexpression of STC1 results in increased expression of MTMG in U-87 MG cells,which could be one of the mechanisms that underlying the fact that STC1 can increase the resistance of GBM cells to TMZ treatment.Our study shows the efficiency of the three-dimensional soft fibrin gel system in the enrichment of GSC,and the results of RNA-Seq reveal some of the molecules and pathways that may play an important role in GSC.Our experiments have also proved that STC1 can promote the stemness characteristics of glioma cells and play a very important role in resisting TMZ.However,the specific mechanism of STC1 enhancing the resistance of glioma cells to TMZ treatment needs further exploration.