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An Encapsulation of Gene Signatures for Hepatocellular Carcinoma, MicroRNA-132 Predicted Target Genes and the Corresponding Overlaps.

ABSTRACT: Previous studies have demonstrated that microRNA-132 plays a vital part in and is actively associated with several cancers, with its tumor-suppressive role in hepatocellular carcinoma confirmed. The current study employed multiple bioinformatics techniques to establish gene signatures for hepatocellular carcinoma, microRNA-132 predicted target genes and the corresponding overlaps.Various assays were performed to explore the role and cellular functions of miR-132 in HCC and a successive panel of tasks was completed, including NLP analysis, miR-132 target genes prediction, comprehensive analyses (gene ontology analysis, pathway analysis, network analysis and connectivity analysis), and analytical integration. Later, HCC-related and miR-132-related potential targets, pathways, networks and highlighted hub genes were revealed as well as those of the overlapped section.MiR-132 was effective in both impeding cell growth and boosting apoptosis in HCC cell lines. A total of fifty-nine genes were obtained from the analytical integration, which were considered to be both HCC- and miR-132-related. Moreover, four specific pathways were unveiled in the network analysis of the overlaps, i.e. adherens junction, VEGF signaling pathway, neurotrophin signaling pathway, and MAPK signaling pathway.The tumor-suppressive role of miR-132 in HCC has been further confirmed by in vitro experiments. Gene signatures in the study identified the potential molecular mechanisms of HCC, miR-132 and their established associations, which might be effective for diagnosis, individualized treatments and prognosis of HCC patients. However, combined detections of miR-132 with other bio-indicators in clinical practice and further in vitro experiments are needed.

SUBMITTER: Zhang X

PROVIDER: S-EPMC4965135 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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An Encapsulation of Gene Signatures for Hepatocellular Carcinoma, MicroRNA-132 Predicted Target Genes and the Corresponding Overlaps.

Zhang Xin X Tang Wei W Chen Gang G Ren Fanghui F Liang Haiwei H Dang Yiwu Y Rong Minhua M

PloS one 20160728 7

<h4>Objectives</h4>Previous studies have demonstrated that microRNA-132 plays a vital part in and is actively associated with several cancers, with its tumor-suppressive role in hepatocellular carcinoma confirmed. The current study employed multiple bioinformatics techniques to establish gene signatures for hepatocellular carcinoma, microRNA-132 predicted target genes and the corresponding overlaps.<h4>Methods</h4>Various assays were performed to explore the role and cellular functions of miR-13 ...[more]

PMID: 27467251

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Project description:AimMolecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs).MethodsWe investigated the expression pattern of 13 miRNAs in purified CD133+ cells separated from the peripheral blood of healthy volunteers, chronic hepatitis C (CHC), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients a long with bone marrow samples from the healthy volunteers and the LC patients using custom miScript miRNA PCR array.ResultsThe differential expression of the 13 studied miRNAs in CD133+ cells separated from the HCC patients' peripheral blood compared to the controls revealed that miR-602, miR-181b, miR-101, miR-122, miR-192, miR-125a-5p, and miR-221 were significantly up regulated (fold change = 1.8, 1.7, 2, 5.4, 1.6, 2.9 & 1.5 P value = 0.039, 0.0019, 0.0013, 0.0370, 00024, 0.000044 &0.000007 respectively). As for the HCC group compared to the CHC group; miR-602, miR-122, miR-181b, miR-125a-5p, and miR-192 were significantly up regulated (fold change = 13, 3.1, 2.8, 1.6 & 1.56, P value = 0.01, 0.001, 0.000004, 0.002 & 0.007 respectively). Upon comparing the HCC group to the LC group; miR-199a-3p, miR-192, miR-122, miR-181b, miR-224, miR-125a-5p, and miR-885-5p were significantly up regulated (fold change = 5, 6.7, 2.3, 3, 2.5, 4.2 & 39.5 P value = 0.001025, 0.000024, 0.000472, 0.000278, 0.000004, 0.000075 & 0.0000001 respectively) whereas miR-22 was significantly down regulated (fold change = 0.57 P value = 0.00002). Only, miR-192, miR-122, miR-181b and miR-125a-5p were significant common miRNAs in CD133+ cells of the HCC group compared to the other non-malignant groups.ConclusionWe identified a miRNA panel comprised of four miRNAs (miR-192, miR-122, miR-181b and miR-125a-5p) that may serve as a molecular tool for characterization of the CD133+ cells associated with different stages of hepatocarinogensis. This panel may aid in developing a new target therapy specific for those CD133+ cells.

Project description:Cancer-associated fibroblasts (CAFs) contribute to tumor progression, and microRNAs (miRs) play an important role in regulating the tumor-promoting properties of CAFs. The objectives of this study were to clarify the specific miR expression profile in CAFs of hepatocellular carcinoma (HCC) and identify its target gene signatures. Small-RNA-sequencing data were generated from nine pairs of CAFs and para-cancer fibroblasts isolated from human HCC and para-tumor tissues, respectively. Bioinformatic analyses were performed to identify the HCC-CAF-specific miR expression profile and the target gene signatures of the deregulated miRs in CAFs. Clinical and immunological implications of the target gene signatures were evaluated in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA_LIHC) database using Cox regression and TIMER analysis. The expressions of hsa-miR-101-3p and hsa-miR-490-3p were significantly downregulated in HCC-CAFs. Their expression in HCC tissue gradually decreased as HCC stage progressed in the clinical staging analysis. Bioinformatic network analysis using miRWalks, miRDB, and miRTarBase databases pointed to TGFBR1 as a common target gene of hsa-miR-101-3p and hsa-miR-490-3p. TGFBR1 expression was negatively correlated with miR-101-3p and miR-490-3p expression in HCC tissues and was also decreased by ectopic miR-101-3p and miR-490-3p expression. HCC patients with TGFBR1 overexpression and downregulated hsa-miR-101-3p and hsa-miR-490-3p demonstrated a significantly poorer prognosis in TCGA_LIHC. TGFBR1 expression was positively correlated with the infiltration of myeloid-derived suppressor cells, regulatory T cells, and M2 macrophages in a TIMER analysis. In conclusion, hsa-miR-101-3p and hsa-miR-490-3p were substantially downregulated miRs in CAFs of HCC, and their common target gene was TGFBR1. The downregulation of hsa-miR-101-3p and hsa-miR-490-3p, as well as high TGFBR1 expression, was associated with poor clinical outcome in HCC patients. In addition, TGFBR1 expression was correlated with the infiltration of immunosuppressive immune cells.

Dataset Information

An Encapsulation of Gene Signatures for Hepatocellular Carcinoma, MicroRNA-132 Predicted Target Genes and the Corresponding Overlaps.

Publications

An Encapsulation of Gene Signatures for Hepatocellular Carcinoma, MicroRNA-132 Predicted Target Genes and the Corresponding Overlaps.

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