Identification of miR-101-3p targets and functional features based on bioinformatics, meta-analysis and experimental verification in hepatocellular carcinoma - PubMed (original) (raw)
. 2017 May 15;9(5):2088-2105.
eCollection 2017.
Affiliations
- PMID: 28559963
- PMCID: PMC5446495
Identification of miR-101-3p targets and functional features based on bioinformatics, meta-analysis and experimental verification in hepatocellular carcinoma
Chun-Yao Li et al. Am J Transl Res. 2017.
Abstract
Background: MiR-101-3p has been reported to suppress invasion and metastasis in hepatocellular carcinoma (HCC) cells. However, the relevant mechanisms are still unclear. The research seeks to determine systematic value of miR-101-3p in HCC, and comprehensively summarize the predicted target genes as well as their potential function, pathways and networks in HCC.
Methods: The miR-101-1 profiles in 353 HCC patients from The Cancer Genome Atlas (TCGA) were analyzed. Meta-analysis was performed to estimate relationship of miR-101 (including precursor and mature miR-101) with clinical features and prognosis in HCC. Further, the promising targets of miR-101-3p were predicted and followed with Gene Ontology (GO), pathway and network analysis. In addition, the functional impact of miR-101-3p was confirmed with in vitro experiments in HCC cells.
Results: In TCGA data, low-expression of miR-101-1 might be a diagnostic (AUC: 0.924, 95% CI: 0.894-0.953) and prognostic (HR=1.55) marker for HCC. Down-regulated miR-101-1 also correlated with poor differentiation, advanced TNM stage, lymph node metastasis and high AFP level of HCC. Meta-analysis revealed that miR-101 down-regulation were associated with poor prognosis, high AFP level and advanced TNM stage of HCC. Moreover, 343 hub genes were filtered and miR-101-3p may be involved in intracellular signaling cascade, transcription, metabolism and cell proliferation. Focal adhesion and pathways in cancer were also significantly enriched. In vitro experiments demonstrated that miR-101-3p inhibited proliferation and promoted apoptosis in HCC cells.
Conclusions: MiR-101-1 may be a prospective biomarker for diagnosis and prognosis of HCC. Potential targets of miR-101-3p could regulate genesis and development of HCC. The data offers insights into biological significances and promising targets of miR-101-3p for further investigation and potential therapies in HCC.
Keywords: Hepatocellular carcinoma; bioinformatics; mechanisms; miR-101-3p; targets.
Conflict of interest statement
None.
Figures
Figure 1
Clinical significance of miR-101-1 in HCC with TCGA data sets. A. MiR-101-1 was obviously downregulated in HCC compared with non-tumor liver tissues; B. ROC curve analysis of miR-101-1 for discriminating HCC from non-tumor liver tissues; C. Kaplan-Meier survival curves showed that lower expression of miR-101-1 with worse survival of HCC patients.
Figure 2
Flow chart of literature selection.
Figure 3
Meta-analysis of miR-101 (including precursor and mature miR-101) expression in HCC patients. A and D. Forest plot and Begg’s funnel plot analysis of miR-101 low expression with AFP level; B and E. Forest plot and Begg’s funnel plot analysis of miR-101 low expression with TNM stage; C and F. Forest plot and Begg’s funnel plot analysis in down-regulated expression of miR-101 with poor prognosis.
Figure 4
Flow chart of target genes selection.
Figure 5
Top 10 GO functional annotation of miR-101-3p targeted genes by DAVID.
Figure 6
KEEG pathways enriched for miR-101-3p targeted genes by DAVID. The statistical significance level (_P_-value) was negative 10-based log transformed.
Figure 7
The constructed networks of miR-101-3p targeted genes by Cytoscape, including biological process (BP), cellular component (CC) and molecular function (MF) networks. Node’s color and size represents the significance of interactions.
Figure 8
Cycle and apoptosis were effected by miR-101-3p in HepG2 cells. A, C. MiR-101-3p mimics and inhibitor effect on cell cycle, cell cycle was arrested in S phase with the effect of miR-101-3p inhibitor and in G0/G1 phase in miR-101-3p mimics transfected group; B, C. MiR-101-3p mimics and inhibitor effect on cell apoptosis, miR-101-3p overexpressed induced apoptosis and opposite result with miR-101-3p inhibitor transfection. Annotation: NC, negative control.
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