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miR-15b-5p has frequently been reported to function as a biomarker in some malignancies; however, the function of miR-15b-5p in hepatocellular carcinoma (HCC) and its molecular mechanism are still not well understood. The present study was designed to confirm the clinical value of miR-15b-5p and further explore its underlying molecular mechanism. A comprehensive investigation of the clinical value of miR-15b-5p in HCC was investigated by data mining The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets as well as literature. In addition, intersected target genes of miR-15b-5p were predicted using the miRWalk database and differentially expressed genes of HCC from TCGA. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out. Then, a protein-protein interaction network (PPI) was constructed to reveal the interactions between some hub target genes of miR-15b-5p. The miR-15b-5p expression level in HCC was predominantly overexpressed compared with non-HCC tissues samples (SMD=0.618, 95% CI: 0.207, 1.029; P<0.0001) based on 991 HCC and 456 adjacent non-HCC tissue samples. The pooled summary receiver operator characteristic (SROC) of miR-15b-5p was 0.81 (Q*=0.74), and the pooled sensitivity and specificity of miR-15b-5p in HCC were 72% (95% CI: 69–75%) and 68% (95% CI: 65–72%), respectively. Bioinformatically, 225 overlapping genes were selected as prospective target genes of miR-15b-5p in HCC, and profoundly enriched GO terms and KEGG pathway investigation in silico demonstrated that the target genes were associated with prostate cancer, proximal tubule bicarbonate reclamation, heart trabecula formation, extracellular space, and interleukin-1 receptor activity. Five genes (ACACB, RIPK4, MAP2K1, TLR4 and IGF1) were defined as hub genes from the PPI network. The high expression of miR-15b-5p could play an essential part in hepatocarcinogenesis through diverse regulation approaches. [ABSTRACT FROM AUTHOR]

In order to determine the diagnostic efficacy of microRNA (miR)-122-5p and to identify the potential molecular signaling pathways underlying the function of miR-122-5p in hepatocellular carcinoma (HCC), the expression profiles of data collected from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and literature databases were analyzed, along with any associations between clinicopathological characteristics and the diagnostic value of miR-122-5p in HCC. The intersection of 12 online prediction databases and differentially expressed genes from TCGA and GEO were utilized in order to select the prospective target genes of miR-122-5p in HCC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI) analyses were subsequently performed based on the selected target genes. The average expression level of miR-122-5p was decreased in HCC patients compared with controls from TCGA database (P<0.001), and the downregulation of miR-122-5p was significantly associated with HCC tissues (P<0.001), tumor vascular invasion (P<0.001), metastasis (P=0.001), sex (P=0.006), virus infection status (P=0.001) and tissue (compared with serum; P<0.001) in cases from the GEO database. The pooled sensitivity and specificity for miR-122-5p to diagnose HCC were 0.60 [95% confidence interval (CI), 0.48–0.71] and 0.81 (95% CI, 0.70–0.89), respectively. The area under the curve (AUC) value was 0.76 (95% CI, 0.72–0.80), while in Meta-DiSc 1.4, the AUC was 0.76 (Q*=0.70). The pooled sensitivity and specificity were 0.60 (95% CI, 0.57–0.62) and 0.79 (95% CI, 0.76–0.81), respectively. A total of 198 overlapping genes were selected as the potential target genes of miR-122-5p, and 7 genes were defined as the hub genes from the PPI network. Cell division cycle 6 (CDC6), minichromosome maintenance complex component 4 (MCM4) and MCM8, which serve pivotal functions in the occurrence and development of HCC, were the most significant hub genes. The regulation of cell proliferation for cellular adhesion and the biosynthesis of amino acids was highlighted in the GO and KEGG pathway analyses. The downregulation of miR-122-5p in HCC demonstrated diagnostic value, worthy of further attention. Therefore, miR-122-5p may function as a tumor suppressor by modulating genome replication. [ABSTRACT FROM AUTHOR]

Background To practically verify the clinical value of miR-26a-5p and thoroughly explore its target genes as well as its potential functions in hepatocellular carcinoma (HCC). Methods HCC and adjacent non-cancerous hepatic tissues of 95 HCC patients were collected for analysis using reverse transcription quantitative real-time PCR (qRT-PCR). For the bioinformatics analysis, we identified potential target genes for miR-26a-5p from differentially expressed genes (DEGs) in Gene Expression Omnibus (GEO) data sets and miRWalk predicted database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein–protein interaction (PPI) analyses were applied to analyze the prospective mechanisms of the predicted target genes. Results MiR-26a-5p showed a significantly lower expression level in HCC tissues (1.56 ± 1.07) than adjacent benign liver tissues (2.28 ± 1.06, P < 0.001). The area under the curve (AUC) of the receiver operating characteristic (ROC) was 0.665 (95% CI: 0.588–0.743, P < 0.001). Significant correlations between miR-26a-5p expression and clinicopathological features such as gender (r = 0.275, P < 0.01), clinical TNM stage (r = −0.306, P < 0.01), and metastasis (r = −0.321, P < 0.01) were observed. To examine potential target genes, we obtained 175 genes for further function analysis, by attaining the intersection of 2062 up-regulated DEGs and 1390 online-predicted target genes. The GO and KEGG pathway annotation indicated focal adhesion, regulation of actin cytoskeleton and the PI3K-Akt signaling pathway as significant prospective mechanisms. The PPI network indicated that NRAS was the most essential hub gene in the whole network. Conclusion Down-regulated miR-26a-5p was closely correlated with the status of metastasis and the progression of HCC. MiR-26a-5p might play protective roles by targeting diverse genes and pathways. [ABSTRACT FROM AUTHOR]