Integrative Analysis of miRNA-mediated Competing Endogenous RNA Network Reveals the lncRNAs-mRNAs Interaction in Glioblastoma Stem Cell Differentiation

Abstract

Background: Competing endogenous RNA (ceRNA) networks play a pivotal role in tumor diagnosis and progression. Numerous studies have explored the functional landscape and prognostic significance of ceRNA interaction within differentiated tumor cells. Objective: We propose a new perspective by exploring ceRNA networks in the process of glioblastoma stem cell (GSC) differentiation. Methods: In this study, expression profiles of lncRNAs and mRNAs were compared between GSCs and differentiated glioblastoma cells. Using a comprehensive computational method, miRNAmediated and GSC differentiation-associated ceRNA crosstalk between lncRNAs and mRNAs was identified. A ceRNA network was then established to select potential candidates that regulate GSC differentiation. Results: Based on the specific ceRNA network related to GSC differentiation, we identified lnc MYOSLID: 11 as a ceRNA that regulated the expression of the downstream gene PXN by competitively binding with hsa-miR-149-3p. After Kaplan-Meier (KM) survival analysis, the expression of PXN gene (PPXN = 0.0015) and lnc MYOSLID: 11 (PMYOSLID: 11=0.041) showed significant correlation with glioblastoma in 160 patients from TCGA. Conclusion: This result sheds light on a potential way of studying the ceRNA network, which can provide clues for developing new diagnostic methods and finding therapeutic targets for clinical treatment of glioblastoma.