Dataset Information

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

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?? (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.

SUBMITTER: Gan BL

PROVIDER: S-EPMC6196605 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Gan Bin-Liang BL Zhang Li-Jie LJ Gao Li L Ma Fu-Chao FC He Rong-Quan RQ Chen Gang G Ma Jie J Zhong Jin-Cai JC Hu Xiao-Hua XH

Oncology reports 20181003 6

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 ...[more]

PMID: 30542718

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Project description:Recent studies have indicated that homeobox A3 (HOXA3) functions as a carcinogen in colon cancer and the methylation level of HOXA3 is significantly increased in lung adenocarcinoma (LUAD) tissues. However, at least to the best of our knowledge, few studies to date have been performed on HOXA3 in non-small cell lung cancer (NSCLC). Therefore, further studies on HOXA3 expression in NSCLC and the potential regulatory mechanisms are urgently required. In this study, HOXA3 expression in 55 tissues of cases of NSCLC and corresponding non-lung cancer tissues was detected by reverse transcription-quantitative PCR (RT-qPCR). In addition, the clinical significance of HOXA3 expression in NSCLC was evaluated using the Cancer Genome Atlas (TCGA) database. Bioinformatics analysis was then performed to elucidate the potential molecular mechanisms of action of HOXA3. Furthermore, the potential target microRNAs (miRNAs or miRs) of HOXA3 were predicted using miRWalk2.0. Based on Gene Expression Omnibus (GEO) and TGCA databases, standardized mean difference (SMD) and sROC methods were used for meta-analyses of the expression of potential target miRNAs of HOXA3 in NSCLC to evaluate their association with HOXA3. The results revealed that the HOXA3 expression levels in NSCLC, LUAD and lung squamous cell carcinoma (LUSC) were 0.1130±0.1398, 0.1295±0.16890 and 0.0906±0.0846, respectively. These values were all decreased compared with the normal tissues (0.1877±0.1975, 0.2337±0.2405 and 0.1249±0.0873, respectively, P<0.05). The TCGA database also revealed the low expression trend of HOXA3. The downregulation of HOXA3 may play an important role in the progression and the poor prognosis of LUAD. The TCGA database also suggested that HOXA3 in LUAD and LUSC tissues exhibited certain mutational levels. In addition, the methylation levels in the NSCLC, LUAD and LUSC tissues significantly increased [NSCLC: fold change (FC), 1.3226; P<0.001; LUAD: FC, 1.2712; P<0.001; and LUSC: FC, 1.3786; P<0.001]. According to the analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the co-expression HOXA3 genes were mainly associated with the focal adhesion signalling pathway and the ECM-receptor interaction signalling pathway. Furthermore, the predicted miRNA, miR-372-3p, exhibited a high expression in both the NSCLC and LUAD tissues (P<0.05). On the whole, the findings of this study indicate that low HOXA3 expression may play a certain role in LUAD; however, its association with LUSC still requires further investigation. HOXA3 function may be achieved through different pathways or target miRNAs. However, the specific underlying mechanisms need to be confirmed through various functional studies.

Dataset Information

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

Publications

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

Similar Datasets

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