The Mechanism Of OLFML2A Regulating The Cell Cycle Of Brain Glioma

Background:By clarifying the influence of OLFML2 A on the cell cycle of glioma,exploring the molecular mechanism of OLFML2 A regulating the cell cycle of glioma,confirming the intermediate molecules of OLFML2 A regulating the cell cycle,and evaluating the relationship between the key molecules in this signaling mechanism and the clinical prognosis of glioma patients,we aimed to provide a theoretical basis for intervening in the cell cycle for the treatment of glioma.Methods:1.Bioinformatics analysis was used to evaluate the expression levels of OLFML2 A,TSC22D1and CDK4 in glioma tissues and their correlation with clinical factors.2.Flow cytometry was performed to analyze the changes in cell cycle in glioma cells after knockdown OLFML2 A by lentiviral vectors,and we detected the expression changes of TSC22D1 and CDK4 were through Western Blot and q RT-PCR.3.Rescue experiments was designed with a TSC22D1 inhibitor to verify the specific mechanism by which OLFML2 A regulates the cell cycle.4.Intracranial tumor transplantation nude mouse models were constructed to assess the effect of knocking down OLFML2 A on glioma cells in vivo.Results:1.Compared to normal brain tissue,OLFML2 A is significantly upregulated in glioma tissue,and its upregulation indicated poor prognosis for patients.2.After knocking down OLFML2 A,the proportion of G1 phase cells in the glioma cells increased,while the proportion of S phase cells decreased compared to the control group,and glioma cells of the OLFML2 A knockdown group has a weakened ability to proliferate.3.Knocking down OLFML2 A also reduced the expression of CDK4,a key molecule at the G1/S checkpoint in glioma cells.4.Compared to normal brain tissue,TSC22D1 was significantly downregulated in glioma tissue,and its downregulation indicated poor prognosis for patients.5.Knocking down OLFML2 A significantly increased TSC22D1 expression in glioma cells.6.Adding TSC22D1 inhibitor to the OLFML2 A knockdown cell culture system could partly reverse the effects caused by knocking down OLFML2 A.7.Animal transplantation experiments confirmed that knocking down OLFML2 A inhibited tumor growth in vivo,and increased TSC22D1 expression level while inhibiting CDK4 expression level.Conclusion: OLFML2 A could affect glioma cell cycle and proliferation by upregulating CDK4 expression level both in vitro and in vivo.The mechanism of this effect is that OLFML2 A could downregulate the expression level of TSC22D1.