No abstract

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.

Previous studies have investigated the association between HOXA13 and non-small cell lung cancer. However, the role of HOXA13 expression in the occurrence and progression of lung adenocarcinoma (LUAD) has not yet been investigated. In the present study, HOXA13-related data mining of The Cancer Genome Atlas (TCGA), polymerase chain reaction (PCR) data from our cases and the case information in Oncomine was conducted for validation. The expression data of HOXA13 in lung cancer cell lines were also collected from the Cancer Cell Line Encyclopedia (CCLE) database for further verification. A comprehensive meta-analysis of the expression of HOXA13 was also performed, integrating the data of TCGA, in-house PCR and Oncomine. Genes that were co-expressed with HOXA13 were subsequently identified through cBioPortal and Multi Experiment Matrix (MEM), and the potential role and mechanism of HOXA13 in LUAD was investigated. The expression value of HOXA13 in the LUAD group, which comprised 237 cases, was 3.74±2.694, significantly higher than its expression value in the non-cancerous group (0.92±0.608, P<0.001). The pooled SMD for HOXA13 was 0.346 (95% CI, 0.052–0.640; P=0.068; I2=51.3%; P=0.021), The meta-analysis of diagnostic tests revealed that the area under the summary receiver operating characteristic curve (SROC) was 0.78 (95% CI, 0.75–0.82). The results demonstrated that HOXA13 is highly expressed in LUAD. In addition to the studies on HOXA13 expression in tissues, the expression data of HOXA13 in lung cancer cell lines were also collected from the CCLE database for further verification of these conclusions. Genes that were co-expressed with HOXA13 were identified for pathway analysis. The most enriched Gene Ontology terms in the genes co-expressed with HOXA13 were positive regulation of transcription from RNA polymerase II promoter, signal transduction and positive regulation of GTPase activity in biological process; cytoplasm, integral component of membrane and plasma membrane in cellular component; and significantly involved in protein binding, transcription factor activity, sequence-specific DNA binding and sequence-specific DNA binding in molecular function. Kyoto Encyclopedia of Genes and Genomes analysis revealed that these target genes were clearly involved in Pathways in cancer, Proteoglycans in cancer and cAMP signaling pathway. The hub genes obtained from the four protein-protein interaction networks were associated with HOXA13. The results of the bioinformatics research in the present study revealed that HOXA13 may influence the expression of these hub genes in such a way as to promote the occurrence and development of LUAD. In conclusion, the expression of HOXA13 in patients with LUAD and its potential clinical value were analyzed comprehensively in the present study using data from a variety of sources. Through bioinformatics analysis, evidence that HOXA13 may promote the occurrence and development of LUAD was obtained.