Clinical significance and potential molecular mechanism of miRNA-222-3p in metastatic prostate cancer

Abstract

ABSTRACT The clinical significance and underlying molecular mechanism of miRNA-222-3p in metastatic prostate cancer (MPCa) remain unclear. The present study used a large number of cases (n = 1,502) based on miRNA chip and miRNA sequencing datasets to evaluate the expression and diagnostic potential of miRNA-222-3p in MPCa. We applied a variety of meta-analytic methods, including forest maps, sensitivity analysis, subgroup analysis and summary receiver operating characteristic curves, to prove the final results. MiRNA-222-3p was reduced in MPCa and had a moderate diagnostic potential in MPCa. We screened 118 miRNA-222-3p targets using three different methods including miRNA-222-3p transfected MPCa cell lines, online prediction databases and differently upregulated genes in MPCa. Moreover, functional enrichment analysis performed to explore the potential molecular mechanism of miRNA-222-3p showed that the potential target genes of miRNA-222-3p were significantly enriched in the p53 signal pathway. In the protein–protein interaction network analysis, SNAP91 was identified as a hub gene that may be closely related to MPCa. Gene chip and RNA sequencing datasets containing 1,237 samples were used to determine the expression level and diagnostic potential of SNAP91 in MPCa. SNAP91 was found to be overexpressed in MPCa and had a moderate diagnostic potential in MPCa. In addition, miRNA-222-3p expression was negatively correlated with SNAP91 expression in MPCa (r = −0.636, P = 0.006). These results demonstrated that miRNA-222-3p might play an important role in MPCa by negatively regulating SNAP91 expression. Thus, miRNA-222-3p might be a potential biomarker and therapeutic target of MPCa.