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. 2015:2015:325176.
doi: 10.1155/2015/325176. Epub 2015 Nov 3.

Clinicopathological Significance of MicroRNA-20b Expression in Hepatocellular Carcinoma and Regulation of HIF-1α and VEGF Effect on Cell Biological Behaviour

Tong-Min Xue  1 , Li-de Tao  2 , Miao Zhang  1 , Jie Zhang  1 , Xia Liu  1 , Guo-Feng Chen  1 , Yi-Jia Zhu  1 , Pei-Jian Zhang  1
Affiliations

Clinicopathological Significance of MicroRNA-20b Expression in Hepatocellular Carcinoma and Regulation of HIF-1α and VEGF Effect on Cell Biological Behaviour

Tong-Min Xue et al. Dis Markers. 2015.

Abstract

miRNA-20b has been shown to be aberrantly expressed in several tumor types. However, the clinical significance of miRNA-20b in the prognosis of patients with hepatocellular carcinoma (HCC) is poorly understood, and the exact role of miRNA-20b in HCC remains unclear. The aim of the present study was to investigate the association of the expression of miR-20b with clinicopathological characteristics and overall survival of HCC patients analyzed by Kaplan-Meier analysis and Cox proportional hazards regression models. Meanwhile, the HIF-1α and VEGF targets of miR-20b have been confirmed. We found not only miR-20b regulation of HIF-1α and VEGF in normal but also regulation of miR-20b in hypoxia. This mechanism would help the tumor cells adapt to the different environments thus promoting the tumor invasion and development. The whole study suggests that miR-20b, HIF-1α, and VEGF serve as a potential therapeutic agent for hepatocellular carcinoma.

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Figures

Figure 1
Figure 1
Comparison of miR-20b expression levels between HCC tissues and normal tissues (P = 0.000).
Figure 2
Figure 2
The correlation between levels of miR-20b and tumor metastasis, TNM stage, tumor recurrence, and microvascular invasion. (a) Tumor metastasis (P = 0.001), TNM stage (P = 0.000), tumor recurrence (P = 0.013), and microvascular invasion (P = 0.048).
Figure 3
Figure 3
Kaplan-Meier survival curve of HCC patients. Patients in the high expression group had significantly poorer prognosis than those in low expression group, analyzed by log-rank tests which are indicated (P = 0.01).
Figure 4
Figure 4
The levels of miR-20b and HIF-1α, VEGF expression after treatment of CoCl2 for 24 h. ∗∗ P < 0.01 compared with normal group.
Figure 5
Figure 5
The transcription efficiency was performed to determine the levels of miR-20b transfected with scrambled miRNA (NC), miR-20b mimics, and miR-20b inhibitor. ∗∗ P < 0.05 compared with control.
Figure 6
Figure 6
miR-20b targeted 3′-UTR of HIF-1α, VEGF mRNA.
Figure 7
Figure 7
Luciferase reporter assay in HepG2 cells. Cells were cotransfection of HepG2 cells with miR-20b mimics and wild-type HIF-1α, VEGF 3′-UTR led to a marked decrease in luciferase activity and cotransfection with miR-20b and mutant HIF-1α, VEGF 3′-UTR had no effect on luciferase activity, and cotransfection with NC miRNA and wild-type HIF-1α, VEGF 3′-UTR or mutant HIF-1α, VEGF 3′-UTR also showed no difference, ∗∗ P < 0.05 compared with negative control.
Figure 8
Figure 8
In hypoxia group showing HIF-1α, VEGF decreased after miR-20b treated transfected. In normal group miR-20b inhibitor increased HIF-1α, VEGF protein by Western blot (a). Use ImageJ to analyze relative expression of proteins (b). ∗∗ P < 0.05 compared with each control group.
Figure 9
Figure 9
The cells viability detected by MTS assays. HepG2 cells were transfected with miR-20b mimics, miR-20b inhibitor, inhibitor + si-HIF-1α, and inhibitor + si-VEGF. Inhibitor + si-HIF-1α: miR-20b inhibitor + HIF-1α-siRNA; inhibitor + si-VEGF: miR-20b inhibitor + VEGF-siRNA. ∗∗ P < 0.01 compared with control.
Figure 10
Figure 10
The cells apoptosis detected by Annexin V-FITC/PI assay. HepG2 cells were transfected with miR-20b inhibitor, inhibitor + si-HIF-1α, and inhibitor + si-VEGF. Inhibitor + si-HIF-1α: miR-20b inhibitor + HIF-1α-siRNA; inhibitor + si-VEGF: miR-20b inhibitor + VEGF-siRNA. ∗∗ P < 0.01 compared with control in normoxia (a). Transfected miR-20b mimics for 24 h in mimetic hypoxia conditions; apoptosis significantly increased in hypoxia conditions (b).
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