MicroRNA?422a functions as a tumor suppressor in glioma by regulating the Wnt/??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 ??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/??catenin signaling axis that plays critical roles in glioma tumorigenesis, and it represents a potential therapeutic target for GBM.

SUBMITTER: Sun J 

PROVIDER: S-EPMC7550978 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature