Background: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma.Methods: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy.Results: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling.Conclusion: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.

Background Obesity is reported to be tightly correlated the development of chronic kidney disease (CKD). However, whether there exists causation is unknown, and it remains controversial about the role of obesity in CKD is protective or destructive. In this study, we try to infer the causal relationship between life course adiposity and CKD, to provide a rationale for obesity management in CKD patients.Methods A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship of life course adiposity traits including including body mass index (BMI), childhood BMI, body fat percentage (BF), birth weight (BW), waist circumference, hip circumference and waist-to-hip ratio (WHR) to CKD. Significant single nucleotide polymorphisms from genome-wide association study on human adiposity traits were utilized as exposure instruments, and summary statistics of CKD as outcome. The causal relationship was evaluated by inverse variance weighted, MR Egger regression and weighted median methods, and further verified by extensive sensitivity analyses.Results Genetically determined one standard deviation increase in adult BMI was associated with higher risk of CKD in all four MR methods. And other indexes including childhood BMI, body fat percentage, and waist/hip circumference also have a causal effect on the risk of CKD. The results were robust under all sensitivity analyses.Conclusions There exist causal effect of life course adiposity on the risk of CKD. A genetic predisposition to higher adult BMI may increase the risk of CKD.

Purpose: Glioma is a common type of malignant tumor in the brain, of which glioblastoma (GBM) is the most aggressive and lethal form. Despite current progress in the clinical treatment, the prognosis of GBM is still not satisfied, mainly due to the genomic alternations and complicated gene regulatory network. MEOX2 was originally identified as a homeobox transcriptional factor, that was reported to play a role in several types of cancers. However, the expression pattern and biological functions of MEOX2 in glioma are not well elucidated. This study aims to clarify the role of MEOX2 in glioma.Methods: Bioinformatic analysis from TCGA and CGGA databases was used to investigate the correlation of MEOX2 with glioma malignancy and clinical prognosis. The expression of MEOX2 was confirmed from clinical samples by qPCR and western blot. Lentivirus-mediated MEOX2 overexpression and knockdown were employed to investigate the biological functions of MEOX2 in glioma malignant behaviors. RNA-seq and signaling investigations were performed to reveal the molecular mechanisms.Results: Bioinformatic data from public databases and our cohort showed that MEOX2 expression was highly associated with glioma malignancy and could predict the poor prognosis. MEOX2 positively regulates glioma cell proliferation, migration/invasion and chemoresistance to temozolomide. Mechanistically, MEOX2 regulates gene profiles related to PI3K/AKT/mTORC1 pathways and thus promotes glioma malignancy.Conclusion: Our work identifies the novel function of MEOX2 in gliomas, and provides a potential target for glioma prognosis and clinical interventions.

Background: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma. Methods: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy. Results: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown increased mitochondrial oxidative damage and decreased pro-survival AKT signaling. Conclusion: Our work identifies the oncogenic role of MTCH2 in gliomas, and establishes the causal relationship between MTCH2 expression and glioma malignancy, which may provide a potential target for future interventions.

Background: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma.Methods: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy.Results: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling.Conclusion: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.