Mechanism And Clinical Significance Of TMEM33 In The Progression Of Glioma

BackgroundGlioma is the most common intracranial malignant tumor.It is one of the most challenging cancers because of its rapid progression.Endoplasmic reticulum stress is considered to play a key role in tumor invasion and progression,and has broad prospects in tumor targeted therapy.Transmembrane specific protein 33（TMEM33）is a new endoplasmic reticulum transmembrane protein molecule and endoplasmic reticulum stress inducing protein,which plays an important role in endoplasmic reticulum stress.In our previous studies,we found that the expression level of TMEM33 was significantly up-regulated in glioma.Therefore,we deeply explore the mechanism and clinical significance of TMEM33 in the progression of glioma.ObjectiveTo study the expression and clinical significance of TMEM33 in glioma;To clarify the mechanism of TMEM33 on glioma proliferation,invasion and immune response by regulating endoplasmic reticulum stress response;It provides potential targets for clinical treatment of glioma.Methods1.The data of 313 patients in the Chinese glioma Genome Atlas（CGGA）database were retrospectively analyzed from the aspects of onset age,molecular typing,pathological grade,IDH mutation,1p / 19 q co deletion and TMEM33 expression level.2.In vitro cultured T98 G and U251 gliomas,si RNA was used to down regulate the expression of TMEM33.The IC50 value was measured by CCK8.3.The effects of TMEM33 expression on cell cycle and apoptosis of T98 G and U251 glioma cells were detected by flow cytometry.4.Western blotting was used to detect the effect of tmem33 expression on perk and ire1 a signaling pathways;The expression level of PD-L1 was detected to determine the effect of TMEM33 on cellular immune response.Results1.By analyzing the information of 313 patients with glioma in CGGA database,the results showed that the expression level of TMEM33 was higher in WHO grade III and IV（P < 0.05）;In different molecular types,the expression level of TMEM33 in glioblastoma was higher（P < 0.05）;The survival time of glioma patients in the low expression group of TMEM33 was significantly longer than that in the high expression group（P < 0.001）;High expression of tmem33 is a factor that increases the risk of death in patients with glioma（HR 1.974,P < 0.001）.2.The results of CCK8 showed that the proliferation activity of glioma cells with low expression of TMEM33 was lower（P < 0.001）;The results of Edu and colony formation experiment showed that down-regulation of tmem33 could significantly inhibit the proliferation and differentiation of glioma cells;3.The results of flow cytometry showed that down regulating the expression of TMEM33 could induce glioma apoptosis（P < 0.001）.4.Western blotting showed that after down regulating TMEM33,it increased the expression of IRE1 signal pathway,inhibited the expression of PERK signal pathway and inhibited the expression of PD-L1 protein.ConclusionsTMEM33 affects the development of glioma cells by regulating endoplasmic reticulum stress response.It is an influencing factor affecting the survival and prognosis of glioma patients and the target of drug therapy.