A Proteomic Approach Reveals That miR-423-5p Modulates Glucidic and Amino Acid Metabolism in Prostate Cancer Cells

Recently, we have demonstrated that miR-423-5p modulates the growth and metastases of prostate cancer (PCa) cells both in vitro and in vivo. Here, we have studied the effects of miR-423-5p on the proteomic profile in order to identify its intracellular targets and the affected pathways. Applying a quantitative proteomic approach, we analyzed the effects on the protein expression profile of miR-423-5p-transduced PCa cells. Moreover, a computational analysis of predicted targets of miR-423-5p was carried out by using several target prediction tools. Proteomic analysis showed that 63 proteins were differentially expressed in miR-423-5-p-transfected LNCaP cells if compared to controls. Pathway enrichment analysis revealed that stable overexpression of miR-423-5p in LNCaP PCa cells induced inhibition of glycolysis and the metabolism of several amino acids and a parallel downregulation of proteins involved in transcription and hypoxia, the immune response through Th17-derived cytokines, inflammation via amphorin signaling, and ion transport. Moreover, upregulated proteins were related to the S phase of cell cycle, chromatin modifications, apoptosis, blood coagulation, and calcium transport. We identified seven proteins commonly represented in miR-423-5p targets and differentially expressed proteins (DEPs) and analyzed their expression and influence on the survival of PCa patients from publicly accessible datasets. Overall, our findings suggest that miR-423-5p induces alterations in glucose and amino acid metabolism in PCa cells paralleled by modulation of several tumor-associated processes.

Automated summary

Recently, we have shown that miR-423-5p influences the growth and metastasis of prostate cancer cells. In this study, we investigated the effects of miR-423-5p on the proteomic profile to identify its targets and affected pathways. Proteomic analysis revealed differential expression of 63 proteins in miR-423-5p-transfected cells, and pathway enrichment analysis showed inhibition of glycolysis and amino acid metabolism, along with downregulation of proteins involved in transcription, hypoxia, immune response, inflammation, and ion transport. We also identified seven proteins commonly targeted by miR-423-5p and differentially expressed proteins, and analyzed their expression and impact on patient survival. Overall, miR-423-5p induces alterations in metabolism and tumor-associated processes in prostate cancer cells.