[Interaction of SENP6 with PINK1 Promotes Temozolomide Resistance in Neuroglioma Cells via Inducing the Mitophagy].

Temozolomide resistance is a major cause of recurrence and poor prognosis in neuroglioma. Recently, growing evidence has suggested that mitophagy is involved in drug resistance in various tumor types. However, the role and molecular mechanisms of mitophagy in temozolomide resistance in glioma remain unclear. In this study, mitophagy levels in temozolomide-resistant and -sensitive cell lines were evaluated. The mechanisms underlying the regulation of mitophagy were explored through RNA sequencing, and the roles of differentially expressed genes in mitophagy and temozolomide resistance were investigated. We found that mitophagy promotes temozolomide resistance in glioma. Specifically, small ubiquitin-like modifier specific protease 6 (SENP6) promoted temozolomide resistance in glioma by inducing mitophagy. Protein-protein interactions between SENP6 and the mitophagy executive protein PTEN-induced kinase 1 (PINK1) resulted in a reduction in small ubiquitin-like modifier 2 (SUMO2)ylation of PINK1, thereby enhancing mitophagy. Our study demonstrates that by inducing mitophagy, the interaction of SENP6 with PINK1 promotes temozolomide resistance in glioblastoma. Therefore, targeting SENP6 or directly regulating mitophagy could be a potential and novel therapeutic target for reversing temozolomide resistance in glioma.

[Study on the correlation between subgroup of blood lipid with degree of coronary artery stenosis in patients with coronary atherosclerotic heart disease].

Objective: To study the correlation between low-density lipoprotein particles (LDL-P) with other lipoprotein indexes. To explore the correlation between LDL-P and its subgroup particles(LDL1-P-LDL6-P) with the degree of coronary artery stenosis in patients with coronary atherosclerotic heart disease(CHD) combining with the result of coronary arteriography. To explore the value of lipoprotein subgroup granules in preventing the severity of coronary artery stenosis in CHD patients. Methods: Cross-sectional study. A total of 259 patients without lipid-lowering drugs for coronary angiography in the department of cardiology of TEDA International Cardiovascular Hospital during 3 months from August 2019 to December 2019 were collected, and 52 healthy subjects were recruited during the same period. The level of high sensitivity C-reactive protein (hs-CRP) and other biochemical indexes were detected by automatic biochemical analyzer. The level of LDL-P and other biochemical indexes were detected by nuclear magnetic resonance spectroscopy(NMRS). The relation between various biomarkers levels with coronary artery stenosis degree was analyzed. Analysis of variance and nonparametric tests were used to compare the differences of indexes among each group. Pearson correlation analysis was used to determine the correlation among the measured indexes. Logistic regression was used for multi-factor analysis, ROC curve was used to evaluate the diagnostic value of related indexes. Results: LDL-P was highly correlated with low-density lipoprotein cholesterol (LDL-C),apolipoprotein B (ApoB) and total cholesterol (TC) (r= 0.927, P<0.001; r=0.921, P<0.001; r=0.844, P<0.001). LDL-P, LDL4-P, LDL5-P and LDL6-P in patients with severe coronary stenosis were higher than those in patients with mild coronary stenosis(U=4 172.000, Z=4.256, P<0.001; t=2.573, P=0.011; U=3 995.000, Z=4.621, P<0.001;t=5.223, P<0.001), LDL-P and LDL6-P were higher than those of patients with moderate coronary stenosis (U=1 159.000, Z=2.294, P=0.022; t=2.075, P=0.041). High levels of hs-CRP, LDL5-P and LDL6-P were risk factors for the degree of coronary stenosis(OR=1.095, P=0.036;OR=1.015, P=0.046;OR=1.012, P=0.039). ROC analysis showed that the AUC of LDL-P, LDL5-P and LDL6-P on coronary stenosis was 0.67, 0.68 and 0.69, respectively. Hs-CRP combined with LDL5-P and LDL6-P had the greatest effect on the degree of coronary stenosis (AUC= 0.70). Conclusions: LDL-P is highly correlated with LDL-C. The levels of LDL-P and LDL6-P were significantly higher in patients with severe stenosis than in patients with mild and moderate stenosis. hs-CRP, LDL5-P and LDL6-P can be used as new risk factors for the degree of coronary stenosis and may be further used as risk predictors. The combined detection of hs-CRP, LDL5-P and LDL6-P is helpful for the diagnosis of the severity of coronary stenosis, and may further become risk predictors.