title: PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway.
abstract: Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p. Overexpression of PRRT2 strongly impaired the cell viability and promoted cell apoptosis and these anti-tumor effects could be largely reversed by microRNA-30a-5p. Mechanistically, PRRT2 expression was closely correlated genes involved in unfolded protein response (UPR) pathway and introduction of PRRT2 inhibited gene expression in the three branches of UPR, including PERK axis, IRE1 axis and ATF6 axis. Taken together, our findings identify PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention.
authors.affiliation: Department of Neurology, Dong Ying People's Hospital, Dongying City 257091, Shan dong Province, PR China. Electronic address: docghbi12@126.com.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Bi
authors.affiliation: Department of Neurosurgery, Dong Ying People's Hospital, Dongying City 257091, Shan dong Province, PR China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Endocrinology, Dong Ying People's Hospital, Dongying City 257091, Shan dong Province, PR China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Obstetrics, Dong Ying People's Hospital, Dongying City 257091, Shan dong Province, PR China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Qu
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D015398:Signal Transduction / Q000235:genetics; D056811:Unfolded Protein Response / Q000235:genetics*; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; C546086:MIRN30b microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human; C460640:EIF2AK3 protein, human; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D012194:RNA-Directed DNA Polymerase; D004722:Endoribonucleases
keywords: GBM; PRRT2; Unfolded protein response; microRNA-30a-5p