Autophagy-Associated Markers LC3-II, ULK2 and microRNAs miR-21, miR-126 and miR-374 as a Potential Prognostic Indicator for Glioma Patients

Abstract

Autophagy has a dual role in gliomagenesis in a microRNA modulated environment. We investigated the potential relevance of autophagy in glioma development and survival by exploring the association of autophagy-associated genes and microRNAs in low- and high-grade gliomas. Real-time PCR (qPCR) was used to determine the expression of genes and microRNAs in 50 glioma tissues while Formalin-fixed paraffin-embedded tissues of the same patients were used for immunohistochemistry. The Mann-Whitney U-test test, Spearman correlation test and Kaplan-Meier survival analysis were performed to evaluate the expression, association, and overall survival in patients respectively. The expression of LC3, AKT and miR-21 were increased in high-grade glioma compared to low-grade glioma while ULK2 expression was decreased in high-grade glioma. A strong-positive correlation was observed for ULK2 with UVRAG, PTEN, miR-7 and miR-100, while moderate correlation with mTOR, Beclin1, miR-30, miR-204, miR-374, miR-21 and miR-126 in low grade glioma, while a moderate positive correlation between ULK2 and PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, AKT and miR-374, and between AKT and ULK1, VPS34, UVRAG, and miR-7 in high-grade gliomas. The low ULK2 and LC3 expression group was significantly associated with better overall survival in gliomas while miR-21 overexpression showed a poor prognosis in glioma patients. Therefore, miR-21, ULK2, and LC3 may serve as prognostic biomarkers for survival outcomes in glioblastoma.