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MicroRNA-106b-5p Promotes Hepatocellular Carcinoma Development via Modulating FOG2

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MicroRNA-106b-5p Promotes Hepatocellular Carcinoma Development via Modulating FOG2

Ling-Xiang Yu et al. Onco Targets Ther.

Abstract

Background: A recent study has revealed that miR-106b-5p might promote hepatocellular carcinoma (HCC) stemness maintenance and metastasis by targeting PTEN via PI3K/Akt pathway based on HCC cell lines and animal models. Its clinical relevance remains unknown. Purpose: Herein, we aimed to evaluate associations of miR-106b-5p dysregulation with various clinicopathological features of HCC patients and investigate its functions during HCC progression. Patients and methods: At first, miR-106b-5p expression in 130 pairs of HCC and adjacent normal liver tissues was detected by quantitative PCR. Chi-square test was then performed to determine clinical significance. Further investigations on its functions were performed by miRNA target prediction and validation, as well as cellular experiments. Results: miR-106b-5p levels in HCC tissues were significantly higher than those in the adjacent normal liver tissues (P<0.001). High miR-106b-5p expression was significantly associated with advanced tumor stage (P=0.02) and high tumor grade (P=0.03). In addition, Friend of GATA 2 (FOG2) was identified as a direct target of miR-106b-5p in HCC cells. Moreover, the clinical relevance to HCC progression of the combined high miR-106b-5p and low FOG2 expression was more significant than high miR-106b-5p alone. Functionally, enforced expression of miR-106b-5p reduced FOG2 expression and promoted the proliferation and invasion of HCC cells. Furthermore, co-transfection of FOG2 restored the oncogenic roles of miR-106b-5p over-expression. Conclusion: Our data offer the convincing evidence that miR-106b-5p upregulation may promote the aggressive progression of HCC. miR-106b-5p overexpression may promote HCC cell proliferation and invasion by suppressing FOG2, implying its potentials as a promising therapeutic target for HCC patients.

Keywords: friend of GATA 2; hepatocellular carcinoma; microRNA-106b-5p; prognosis; tumor progression.

Conflict of interest statement

The authors clarified that there were no conflicts of interest in the current study.

Figures

Figure 1
Figure 1
Expression levels of miR-106b-5p in HCC tissues and cells detected by quantitative PCR assay. (A) Expression levels of miR-106b-5p in HCC tissues were significantly higher than those in the adjacent nonneoplastic liver tissues (mean ± S.D.: 2.89±0.80 vs 1.23±0.22, P<0.001). (B) Expression levels of miR-106b-5p in HCC cell lines were significantly higher than those in normal liver cell line (HepG2 vs L-02, mean ± S.D.: 3.04±0.47 vs 1.06±0.31, P<0.001; MHCC-97H vs L-02, mean ± S.D.: 3.33±0.44 vs 1.06±0.31, P<0.001).
Figure 2
Figure 2
FOG2 was a direct target of miR-106b-5p. (A) FOG2 3’UTR contains a miR-106b-5p binding site. (B) The luciferase activities of HepG2 and MHCC-97H cells cotransfected with the FOG2-WT/MUT-3‘-UTR reporter vector and miR-106b-5p/NC mimics (* P<0.05, FOG2-WT-3‘-UTR+miR-106b-5p mimics vs FOG2-MUT-3‘-UTR+miR-106b-5p). (C) Expression levels of FOG2 mRNA in HCC cells (all P<0.01). (D) The Spearman correlation analysis showed that the expression levels of miR-106b-5p in HCC tissues were negatively correlated with those of FOG2 mRNA (r=−0.2992, P=0.005).
Figure S1
Figure S1
Relative expression levels of putative targets of miR-106b-5p.
Figure 3
Figure 3
miR-106b-5p promoted the proliferation and invasion of HCC cells via reducing FOG2 expression. (A) Expression levels of miR-106b-5p in HCC cells with different transfection (** P<0.01, miR-106b-5p mimics vs NC mimics). (B) Expression levels of FOG2 mRNA in HCC cells with different transfection (** P<0.01, miR-106b-5p mimics+FOG2 vs miR-106b-5p mimics+NC, or NC mimics+FOG2 vs NC mimics+NC). (C and D) The cell proliferation of HepG2 and MHCC-97H cells with different transfection. (E and F) The cell invasion abilities of HepG2 and MHCC-97H cells detected by Transwell assay.

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