MiR-877-5p suppresses cell growth, migration and invasion by targeting cyclin dependent kinase 14 and predicts prognosis in hepatocellular carcinoma.

OBJECTIVE: Recent studies reveal that hepatocellular carcinoma (HCC) express aberrant microRNAs. Dysregulation of miR-877-5p has been observed in HCC. The objective of the present study was to explore the clinical significance, function and underlying mechanism of miR-877-5p in HCC. PATIENTS AND METHODS: Quantitative reverse transcription PCR (qRT-PCR) was used to measure the levels of miR-877-5p in HCC specimens and HCC cell lines. Correlations between miR-877-5p expression and the clinicopathological features and prognosis of HCC patients were then evaluated. MTT assays, colony formation assays, scratch test, transwell assays were used to explore the biological function of miR-877-5p in HCC. A luciferase reporter assay and Western blot were conducted to confirm the target gene of miR-877-5p, and the results were validated in HCC cell lines.
RESULTS: We found that the expression of miR-877-5p was downregulated in HCC tissues or cell lines. Clinicopathologic analysis revealed that low miR-877-5p expression correlated with histologic grade (p = 0.008) and TNM stage (p = 0.018). The Kaplan-Meier method indicated that low miR-877-5p levels in HCC were associated with shorter overall survival (p = 0.0041) and disease-free survival (p = 0.0005). Multivariate analysis demonstrated that miR-877-5p expression was an independent poor prognostic factor for HCC patients. Functional assay revealed that upregulation of miR-877-5p could inhibit proliferation, migration, and invasion of HCC cells in vitro. We further identified cyclin-dependent kinase 14 (CDK14) as a direct target of miR-877-5p in HCC cells. Ectopic expression of CDK14 reversed the inhibitory effects of miR-877-5p.
CONCLUSIONS: Low miR-877-5p expression was a poor prognostic factor for HCC patients, and miR-877-5p functioned as a tumor suppressor in HCC cells via targeting CDK14.