Downregulation of miR-224-5p in prostate cancer and its relevant molecular mechanism via TCGA, GEO database and in silico analyses

The function of the expression of microRNA (miR)-224-5p in prostate adenocarcinoma (PCa) remains to be elucidated, therefore, the present study aimed to investigate the clinical significance and potential molecular mechanism of miR-224-5p in PCa. Data on the expression of miR-224-5p in PCa were extracted from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), ArrayExpress and previous literature, and meta-analyses with standardized mean difference (SMD) and summary receiver operating characteristic (sROC) methods were performed for statistical analyses. The prospective target genes of miR-224-5p were collected by overlapping the differentially expressed mRNAs in TCGA and GEO, and target genes predicted by miRWalk2.0. Subsequently, in silico analysis was performed to examine the associated pathways of miR-224-5p in PCa. The expression of miR-224-5p was markedly lower in PCa; the overall SMD was −0.562, and overall sROC area under the curve was 0.80. In addition, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the prospective target genes of miR-224-5p were largely enriched in the amino sugar and nucleotide sugar metabolism signaling pathway, and three genes [UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), hexokinase 2 (HK2) and chitinase 1 (CHIT1)] enriched in this pathway showed higher expression (P<0.05). In addition, key genes in the protein-protein interaction network analysis [DNA topoisomerase 2-α (TOP2A), ATP citrate lyase (ACLY) and ribonucleotide reductase regulatory subunit M2 (RRM2)] exhibited significantly increased expression (P<0.05). The results suggested that the downregulated expression of miR-224-5p may be associated with the clinical progression and prognosis of PCa. Furthermore, miR-224-5p likely exerts its effects by targeting genes, including UAP1, HK2, CHIT1, TOP2A, ACLY and RRM2. However, in vivo and in vitro experiments are required to confirm these findings.