MicroRNA-504 functions as a tumor suppressor in hepatocellular carcinoma through inhibiting Frizzled-7-mediated-Wnt/β-catenin signaling - 20/09/18
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Graphical abstract |
Highlights |
• | miR-504 is downregulated in HCC tissues and cell lines. |
• | miR-504 inhibits HCC cell proliferation and invasion. |
• | miR-504 targets FZD7 3′-UTR and inhibits its expression. |
• | miR-504 regulates the activation of Wnt/β-catenin signaling. |
• | miR-504 inhibits HCC progression by targeting FZD7. |
Abstract |
Accumulating evidence suggests that microRNAs (miRNAs) are critical regulators in the development and progression of various malignant tumors, including hepatocellular carcinoma (HCC). Multiple findings have indicated that miRNA-504 (miR-504) is dysregulated in several types of cancers, functioning as an oncogenic miRNA or a tumor suppressive miRNA. However, the role of miR-504 in HCC remains unknown. In this study, we aimed to detect the expression pattern of miR-504 in HCC tissues and cell lines and investigate the precise biological function in HCC cells. Our results showed that miR-504 expression levels were frequently downregulated in both HCC tissues and cell lines. Gain-of-function experiments demonstrated that miR-504 overexpression inhibited the proliferation and invasion in HCC cell lines. By contrast, miR-504 inhibition had the opposite effect. Interestingly, bioinformatics analysis predicted that Frizzled-7 (FZD7) was a potential target gene of miR-504. Dual-luciferase reporter assays confirmed that miR-504 directly targeted the 3′-untranslated region of FZD7 mRNA. In addition, our results showed that miR-504 negatively regulated the mRNA and protein expression of FZD7 in HCC cell lines. Moreover, miR-540 overexpression inhibited the cellular expression of β-catenin and blocked the activation of Wnt signaling in HCC cells. Notably, restoration of FZD7 expression significantly reversed the inhibitory effect of miR-504 on proliferation, invasion, and Wnt/β-catenin signaling in HCC cells. In conclusion, our results demonstrate that miR-504 functions as a tumor suppressive miRNA that inhibits the proliferation and invasion of HCC cells by targeting FZD7 and inhibiting Wnt/β-catenin signaling. Our study provides evidence that miR-504-meidated FZD7/Wnt/β-catenin signaling pathway plays an important role in HCC development and progression and suggests miR-504 as a novel future therapeutic target for treatment of HCC.
Le texte complet de cet article est disponible en PDF.Abbreviations : FZD7, HCC, mRNA, miRNAs, miR-504, CCK-8, RT-qPCR, 3′-UTR
Keywords : FZD7, Hepatocellular carcinoma, miR-504, Wnt
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Vol 107
P. 754-762 - novembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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