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Erschienen in:
04.10.2016 | Original Article – Cancer Research
MicroRNA-34c-3p promotes cell proliferation and invasion in hepatocellular carcinoma by regulation of NCKAP1 expression
Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2017
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Purpose
Our previous miRNA profiling study indicated that microRNA-34c-3p (miR-34c-3p) was overexpressed and associated with survival in HCC. This study is aimed to confirm its clinical significance and explore the function and underlying mechanism of miR-34c-3p in HCC.
Methods
We first evaluated miR-34c-3p expression and its relationship with prognosis in HCC patients. We then established stable HCC cell lines with miR-34c-3p overexpression and knockdown by the lentiviral packaging systems and performed the functional assays in vitro and in vivo, respectively. We next identified the target of miR-34c-3p by using microRNA target databases and dual-luciferase assay. Finally, the correlation between the expression of miR-34c-3p and the target gene was analyzed by immunohistochemistry and qRT-PCR in HCC tissues and hepatoma xenografts.
Results
Overexpressed miR-34c-3p was confirmed in HCC tissues and significantly associated with poor survival of HCC patients. miR-34c-3p expression was also recognized as an independent risk factor for DFS and OS in multivariate analysis. Ectopic expression of miR-34c-3p significantly promotes the proliferation, colony formation, invasion and cell cycle regression of HCC cell lines. Knockdown of miR-34c-3p remarkably blocked hepatoma growth in the xenograft model. miRNA target databases and luciferase reporter assay showed that NCKAP1 was a direct target of miR-34c-3p in HCC cells and the high expression of NCKAP1 in HCC tissues is significantly correlated with low expression of miR-34c-3p and associated with a favorable prognosis of HCC patients.
Conclusion
The current study demonstrates that miR-34c-3p functions as a tumor promoter by targeting NCKAP1 that is associated with prognosis in HCC. miR-34c-3p and NCKAP1 may be new potential molecular targets for HCC therapy.