MicroRNA‑422a functions as a tumor suppressor in glioma by regulating the Wnt/β‑catenin signaling pathway via RPN2.

Abstract

MicroRNAs (miRs), which act as crucial regulators of oncogenes and tumor suppressors, have been confirmed to play a significant role in the initiation and progression of various malignancies, including glioma. The present study analyzed the expression and roles of miR-422a in glioma, and reverse transcription-quantitative PCR confirmed that miR-422a expression was significantly lower in glioblastoma multiforme (GBM) samples and cell lines compared with the low-grade glioma samples and the H4 cell line, respectively. miR-422a overexpression suppressed proliferation and invasion, and induced apoptosis in LN229 and U87 cell lines. Luciferase reporter assay, western blotting and RNA immunoprecipitation analysis revealed that ribophorin II (RPN2) is a direct functional target of miR-422a. Additionally, the overexpression of RPN2 partially reversed the miR-422a-mediated inhibitory effect on the malignant phenotype. Mechanistic investigation demonstrated that the upregulation of miR-422a inhibited β-catenin/transcription factor 4 transcriptional activity, at least partially through RPN2, as indicated by in vitro and in vivo experiments. Furthermore, RPN2 expression was inversely correlated with miR-422a expression in GBM specimens and predicted patient survival in the Chinese Glioma Genome Atlas, UALCAN, Gene Expression Profiling Interactive Analysis databases. In conclusion, the present data reveal a new miR-422a/RPN2/Wnt/β-catenin signaling axis that plays critical roles in glioma tumorigenesis, and it represents a potential therapeutic target for GBM.