Dataset Information

Clinical value and potential targets of miR-224-5p in hepatocellular carcinoma validated by a TCGA- and GEO- based study.

ABSTRACT: OBJECTIVE:to explore clinical value and potential targets of MicroRNA-224-5p in the tumorigenesis and progression of hepatocellular carcinoma (HCC). METHODS:We evaluated the clinical value of MicroRNA-224-5p from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Meanwhile, target genes of MicroRNA-224-5p were predicted by bioinformatics method. The target genes of MicroRNA-224-5p were finally analyzed in Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and Protein-Protein Interaction (PPI) network annotation. RESULTS:MicroRNA-224-5p expression level in HCC was higher than in non-tumor tissues (SMD=1.24; 95% CI, 0.68 to 1.81; P<0.0001) and MicroRNA-224-5p might represent a diagnostic marker (overall AUC=0.92; 95% CI, 0.90 to 0.94). 262 target genes were acquired by overlapping 4927 genes predicted by more than four computational prediction tools with 1,123 down-regulated DEGs in HCC. Furthermore, gene sets enrichment analysis of the 262 overlapping genes was implemented. The mostly significant GO terms within the overlapping target genes of MicroRNA-224-5p were cellular response to chemical stimulus, plasma membrane part and coenzyme binding. KEGG pathway annotation showed the overlapping genes mostly took part in metabolic pathways. In PPI analysis, one hub gene, GNA14, stood out cause for the significant negative correlation with MicroRNA-224. CONCLUSION:MicroRNA-224-5p is upregulated in HCC and may be a prospective biomarker for diagnosis. Moreover, MicroRNA-224-5p might play an oncogenic role in HCC by targeting GNA14.

SUBMITTER: Zhang L

PROVIDER: S-EPMC6965914 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical value and potential targets of miR-224-5p in hepatocellular carcinoma validated by a TCGA- and GEO- based study.

Zhang Lu L Huang Lanshan L Liang Haiwei H Zhang Rui R Chen Gang G Pang Yuyan Y Feng Zhenbo Z

International journal of clinical and experimental pathology 20170901 9

<h4>Objective</h4>to explore clinical value and potential targets of MicroRNA-224-5p in the tumorigenesis and progression of hepatocellular carcinoma (HCC).<h4>Methods</h4>We evaluated the clinical value of MicroRNA-224-5p from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Meanwhile, target genes of MicroRNA-224-5p were predicted by bioinformatics method. The target genes of MicroRNA-224-5p were finally analyzed in Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Gen ...[more]

PMID: 31966887

Similar Datasets

Project description: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.

Project description:Increasing evidence has demonstrated that microRNA (miR)‑133a‑3p is an important regulator of hepatocellular carcinoma (HCC). In the present study, the diagnostic role of miR‑133a‑3p in HCC, and the potential functional pathways, were both explored based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expression Omnibus (GEO) database and ArrayExpress database. The data related to HCC and matched adjacent normal tissues were also downloaded from The Cancer Genome Atlas (TCGA). Published studies reporting the association between miR‑133a‑3p expression and HCC were reviewed from multiple databases. By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR‑133a‑3p expression and clinicopathological features of HCC. Eventually, putative targets of miR‑133a‑3p in HCC were selected for further bioinformatics prediction. A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR‑133a‑3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=‑0.54; 95% confidence interval (CI), ‑0.74 to ‑0.35; P<0.001]. Consistently, the level of miR‑133a‑1 in HCC was reduced markedly compared to normal tissues (P<0.001) based on TCGA data, and the AUC value of low miR‑133a‑1 expression for HCC diagnosis was 0.670 (P<0.001). Furthermore, the combined SMD of all datasets (GEO, TCGA and literature) suggested that significant difference was observed between the HCC group and the normal control group, and lower miR‑133a‑3p expression in HCC group was noted (SMD=‑0.69; 95% CI, ‑1.10 to ‑0.29; P=0.001). In addition, the authors discovered five key genes of the calcium signaling pathway (NOS1, ADRA1A, ADRA1B, ADRA1D and TBXA2R) that may probably be targeted by miR‑133a‑3p in HCC. The study reveals that miR‑133a‑3p may function as a tumor suppressor in HCC. The prospective novel pathways and key genes of miR‑133a‑3p could offer potential biomarkers for HCC; however, the predictions require further confirmation.

Dataset Information

Clinical value and potential targets of miR-224-5p in hepatocellular carcinoma validated by a TCGA- and GEO- based study.

Publications

Clinical value and potential targets of miR-224-5p in hepatocellular carcinoma validated by a TCGA- and GEO- based study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets