Upregulation of circ-ASPH contributes to glioma cell proliferation and aggressiveness by targeting the miR-599/AR/SOCS2-AS1 signaling pathway

Abstract

Glioma (GM) is the most common type of malignant brain tumor with a high recurrence rate. Circular RNAs (circRNAs) play a key role in mediating tumorigenesis. However, the functions and mechanisms of circRNAs in GM are still not fully understood. A circRNA microarray was performed to identify differentially expressed circRNAs in GM and non-cancerous specimens. Reverse transcription-quantitative PCR was used to detect circ-aspartyl/asparaginyl β-hydroxylase (ASPH) expres- sion in GM tissues and cells. The clinical importance of circ-ASPH was investigated using Kaplan-Meier analysis. The functions of circ-ASPH were investigated in LN229 and U87MG cells. Bioinformatics, RNA immunoprecipitation, RNA pull-down and luciferase reporter assays were used to explore the mechanisms of circ-ASPH in GM. circ-ASPH levels were upregulated in GM specimens and cells. The prognostic role of circ-ASPH was identified in patients with GM. Loss/gain of function assays demonstrated that circ-ASPH increased cell proliferation, migration and inva- sion in GM cells. Mechanistically, circ-ASPH counteracted microRNA (miR)-599-mediated androgen receptor (AR) suppression by acting as a sponge for miR-599. Rescue assays indicated that circ-ASPH facilitated cell progression by regulating AR expression. Moreover, AR activated long non-coding RNA suppressor of cytokine signaling 2-anti- sense RNA 1 (SOCS2-AS1) expression in GM cells. Taken together, circ-ASPH/miR-599/AR/SOCS2-AS1 signaling may be a promising biomarker/therapeutic target for GM.