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Oncogenic value of microRNA-15b-5p in hepatocellular carcinoma and a bioinformatics investigation.

ABSTRACT: 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.

SUBMITTER: Pan WY

PROVIDER: S-EPMC6341845 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Oncogenic value of microRNA-15b-5p in hepatocellular carcinoma and a bioinformatics investigation.

Pan Wen-Ya WY Zeng Jiang-Hui JH Wen Dong-Yue DY Wang Jie-Yu JY Wang Peng-Peng PP Chen Gang G Feng Zhen-Bo ZB

Oncology letters 20181122 2

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 Expres ...[more]

PMID: 30675229

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Project description:To investigate the prospective roles and the clinicopathological application of microRNA-21-5p (miR-21-5p) in hepatocellular carcinoma (HCC), the present review is based on 24 studies and bioinformatics investigation. Firstly, HCC-associated miR-21-5p data were aggregated from literature databases and two public genomic data repositories, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Potential target genes of miR-21-5p in HCC were identified using TCGA and GEO, Natural Language Processing and 14 online software packages. The oncogenic roles of these target genes was probed for understanding using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Hub genes were further investigated by protein-protein interaction network (PPI) analysis. Comprehensive meta-analysis, including 10 microarrays from GEO datasets, 13 literature studies and TCGA-based RNA sequencing data, indicated a reliable diagnostic capacity of miR-21-5p [area under the curve (AUC), 0.887; sensitivity, 0.78% and specificity, 0.79%]. The healthy control group (AUC, 0.926; sensitivity, 0.87% and specificity, 0.82%) demonstrated high diagnostic capacity of miR-21-5p compared with the chronic hepatitis B infection group (AUC, 0.904; sensitivity, 0.75% and specificity, 0.84%). A total of 10 significant enrichment pathways were indicated by KEGG analysis, with cytokine-cytokine receptor interaction exhibiting the highest score. A total of 5 genes, hepatocyte growth factor, forkhead box O1 (FOXO1), thrombospondin 1, estrogen receptor 1 (ESR1) and C-X-C motif chemokine ligand 12 were selected from 39 overlapping genes, according to the PPI network. Target genes were assembled in GO terms associated with 'response to chemical stimulus', 'cell surface' and 'growth factor binding'. In particular, low expression of FOXO1 and ESR1 was associated with miR-21-5p expression. In conclusion, upregulated expression of miR-21-5p may be a functional regulator of the metabolism or apoptosis in HCC and a novel tumor marker for the early diagnosis of HCC.

Project description:Thyroid carcinoma (THCA) is a malignant tumor of the endocrine system. Previous studies have revealed the vital roles of microRNAs (miRNAs/miRs) in THCA procession. The present study aimed to explore the effects of miR?15b?5p on the progression of THCA and its targeting mechanism. The data of THCA and healthy samples were firstly collected from starbase2.0 and used to analyze the relationship of miR?15b?5p with THCA. Dual?luciferase assay was performed to detect the direct interaction between miR?15b?5p and the predicted target gene GDP dissociation inhibitor 2 (GDI2). The effects of miR?15b?5p and GDI2 on the overall survival of patients with THCA were analyzed using Kaplan?Meier analysis with log rank test. Cell Counting Kit?8 and Transwell assays were conducted to assess the impacts of miR?15b?5p and GDI2 on the proliferation and invasion of THCA cells. Reverse transcription?quantitative PCR and western blot analyses were performed to analyze the expression levels of the related miRNAs and proteins, respectively. miR?15b?5p was found to be downregulated both in THCA tissues and cells, and the low expression of miR?15b?5p was associated with the short overall survival time of patients. Moreover, the upregulation or downregulation of miR?15b?5p could inhibit or enhance the proliferation and invasion of THCA cells, respectively. miR?15b?5p reduced the protein expression levels of matrix metalloproteinase (MMP)2 and MMP9, which were related to cell invasion. Furthermore, GDI2, which was enhanced in THCA and related to the poor prognosis of patients with THCA, was identified as the target gene of miR?15b?5p and negatively regulated by miR?15b?5p. Additional experiments demonstrated that GDI2 overexpression could significantly reduce the antitumor effect of miR?15b?5p and its inhibitory action on the expression levels of MMP2 and MMP9. Thus, the results indicated a potential tumor suppressive role of miR?15b?5p in THCA, which was mainly exerted by targeting GDI2 and modulating MMP2 and MMP9. These findings will increase the understanding on the pathogenesis of THCA and provide novel candidates for THCA therapy.

Dataset Information

Oncogenic value of microRNA-15b-5p in hepatocellular carcinoma and a bioinformatics investigation.

Publications

Oncogenic value of microRNA-15b-5p in hepatocellular carcinoma and a bioinformatics investigation.

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