Upregulation of GPNCA is associated with poor prognosis through enhancement of tumor growth via regulating GSK3B

Abstract

AbstractGPNCA is a long non-coding RNA with unknown functions. In this study, using data from 9 cancers obtained from The Cancer Genome Atlas (TCGA), GPNCA was identified as overexpressed in cancer vs. normal tissues. The upregulation of GPNCA was associated with poor overall prognosis in colon, liver, renal clear cell and breast cancers. The upregulation of GPNCA was partly due to enhanced H3K27ac occupancy on its promoter region via EP300 and KAT2A/GCN5. The overexpression of GPNCA was positively related to tumor metastasis in colon cancer and poor disease-free and recurrence-free survival in colon and liver cancer. Both gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis indicated that GPNCA was closely linked to regulation of gene transcription and post-transcriptional modifications, which was further supported by in vitro cell cytoplasmic and nuclear RNA purification assessments. Furthermore, GPNCA was associated with cell growth. Our in vitro experiments demonstrated that GPNCA silencing inhibited tumor growth via inhibiting its nearby gene GSK3B. Taken together, these findings highlight GPNCA as a biomarker for cancer diagnosis and a potential target for future cancer drug development.