Abstract
BackgroundMicroRNAs are considered as potential regulators in various biological pathways and contribute to the diagnosis and prognosis of cancers. MicroRNA-214-3p (miR-214-3p) was proved to be correlated with various cancers in recent studies. However, the biological functions of miR-214-3p in hepatocellular carcinoma (HCC) and its association with the prognosis of HCC after liver transplantation are still unevaluated. Here we intended to elucidate the functional implication of miR-214-3p in regulation of cell proliferation and apoptosis and its potential prediction of clinical prognosis of HCC patients.MethodsExpressions of miR-214-3p in 98 HCC patients and three HCC cell lines were detected by quantitative reverse transcription PCR (qRT-PCR) to explore the association of miR-214-3p expression and clinicopathological characteristics. The effects of miR-214-3p on cell proliferation and apoptosis were examined by proliferation and flow cytometry assay, respectively. The direct target gene of miR-214-3p was also detected by luciferase reporter assay.ResultsThe effects of miR-214-3p on cell proliferation and apoptosis were examined by proliferation and flow cytometry assay, respectively. The direct target gene of miR-214-3p was also detected by luciferase reporter assay. The results showed that miR-214-3p expression was downregulated in primary HCC samples compared with normal liver tissues, and was decreased in HCC recurrence species compared with non-recurrence controls (P = 0.001). Low miR-214-3p level was associated with poor overall survival (OS) (Log rank P = 0.003) and recurrence-free survival (RFS) (Log rank P = 0.007). Moreover, miR-214-3p precursor transfection resulted in decreased cell proliferation, cell cycle arrest at G1 phase, and enhanced cell apoptosis in HepG2 and HUH-7 cells. Further investigation showed that miR-214-3p could regulate its target gene maternal embryonic leucine zipper kinase (MELK) by directly binding to MELK-3′-UTR.ConclusionsmiR-214-3p suppresses HCC progression by directly down-regulating MELK expression, indicating a potential therapeutic target for the treatment and prognosis of HCC patients.
Highlights
MicroRNAs are considered as potential regulators in various biological pathways and contribute to the diagnosis and prognosis of cancers
A better understanding of the molecular mechanisms that can distinguish progressive from non-progressive hepatocellular carcinoma (HCC) is indispensable for exploring novel prognostic markers and therapeutic targets which may guide the surveillance after liver transplantation
Our results showed that miR214-3p exhibited decreased expressions in HCC cell lines compared with L-O2 cells (Fig. 1a)
Summary
MicroRNAs are considered as potential regulators in various biological pathways and contribute to the diagnosis and prognosis of cancers. The biological functions of miR-214-3p in hepatocellular carcinoma (HCC) and its association with the prognosis of HCC after liver transplantation are still unevaluated. We intended to elucidate the functional implication of miR-214-3p in regulation of cell proliferation and apoptosis and its potential prediction of clinical prognosis of HCC patients. Surgical hepatic resection and liver transplantation are still the main curative treatment for HCC patients. Tumor recurrence rates remain a major concern for the exhibition of active hepatitis or cirrhosis in surrounding non-tumor liver tissues, even in patients who have received curative treatments [6, 7]. A better understanding of the molecular mechanisms that can distinguish progressive from non-progressive HCC is indispensable for exploring novel prognostic markers and therapeutic targets which may guide the surveillance after liver transplantation
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