Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumor in digestive system. CircRNAs involve in lots of biological processes through interacting with miRNAs and their targeted mRNA. We obtained the circRNA gene expression profiles from Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) between PDAC samples and paracancerous tissues. Bioinformatics analyses, including GO analysis, KEGG pathway analysis and PPI network analysis, were conducted for further investigation. We also constructed circRNA‑microRNA-mRNA co-expression network. A total 291 differentially expressed circRNAs were screened out. The GO enrichment analysis revealed that up-regulated DEGs were mainly involved metabolic process, biological regulation, and gene expression, and down-regulated DEGs were involved in cell communication, single-organism process, and signal transduction. The KEGG pathway analysis, the upregulated circRNAs were enriched cGMP-PKG signaling pathway, and HTLV-I infection, while the downregulated circRNAs were enriched in protein processing in endoplasmic reticulum, insulin signaling pathway, regulation of actin cytoskeleton, etc. Four genes were identified from PPI network as both hub genes and module genes, and their circRNA‑miRNA-mRNA regulatory network also be constructed. Our study indicated possible involvement of dysregulated circRNAs in the development of PDAC and promoted our understanding of the underlying molecular mechanisms.
Cancer cells usually prefer glycolysis to support their proliferation. Our previous studies have shown that the long palate, lung, and nasal epithelial cell clone 1 (LPLUNC1) can up-regulate prohibitin 1 (PHB1) expression to inhibit the proliferation of nasopharyngeal carcinoma (NPC) cells. Given that PHB1 is an important regulator of cell energy metabolism, we explored whether and how LPLUNC1 regulated glucose glycolysis in NPC cells. LPLUNC1 or PHB1 over-expression decreased glycolysis and increased oxidative phosphorylation (OXPHOS)-related protein expression in NPC cells, accompanied by enhancing PHB1 and 14-3-3σ expression and promoting phosphorylated PHB1 nuclear translocation. Co-immunoprecipitation indicated that 14-3-3σ directly interacted with phosphorylated PHB1. PHB1 Y259A mutant over-expression abrogated the decreasing glycolysis and increasing OXPHOS-related protein expression induced by LPLUNC1 over-expression in NPC cells. LPLUNC1 over-expression also increased p53, but decreased c-Myc expression in NPC cells, which were crucial for the decrease in glycolysis and increase in OXPHOS-related protein expression induced by LPLUNC1 over-expression. Finally, we found that treatment with all-trans retinoic acid (ATRA) reduced the viability and clonogenicity of NPC cells, decreased glycolysis and increased OXPHOS-related protein xpression by enhancing LPLUNC1 expression in NPC cells. Therefore, the LPLUNC1-PHB1-p53/c-Myc axis decreased glycolysis in NPC cells and ATRA up-regulated LPLUNC1 expression, a promising drug for intervention of NPC.
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