Decrease expression of microRNA-20a promotes cancer cell proliferation and predicts poor survival of hepatocellular carcinoma

Abstract

BackgroundGrowing evidences indicate microRNAs play important roles in cancer development, progression, metastasis and may constitute robust biomarkers for cancer prognosis. The aim of this study was to identify the clinical and functional association of microRNA-20a (miR-20a) in hepatocellular carcinoma (HCC).MethodsMiR-20a was detected using Taqman real-time polymerase chain reaction. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-20a with survival of patients. The potential functions of miR-20a on proliferation were evaluated by proliferation and flow cytometry analysis. The direct target gene of miR-20a was also identified by luciferase reporter assays.ResultsMiR-20a was lower in primary HCC than normal liver, and were further decreased in those with post-liver transplantation (LT) HCC recurrence compared with those with non-recurrence (p = 0.001). Patients with lower miR-20a expression had significantly poorer recurrence-free survival (RFS, Log rank p < 0.001) and overall survival (OS, Log rank p < 0.001). Multivariate analysis revealed that lower miR-20a was an independent predictor of poor prognosis. MiR-20a restoration could suppress HepG2 and SMMC-7721 cells proliferation and induce cell cycle G1 arrest and apoptosis. Subsequent investigations revealed that miR-20a directly targeted myeloid cell leukemia sequence 1 (Mcl-1) and reduced the endogenous protein level of Mcl-1 in HCC cells.ConclusionsMiR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Down-regulation of miR-20a increases the proliferation abilities of HCC cells. Our findings suggest miR-20a may represent a novel potential therapeutic target and biomarker for survival of HCC patients.

microRNA-20a enhances the epithelial-to-mesenchymal transition of colorectal cancer cells by modulating matrix metalloproteinases

“…Studies have shown that miR-20a exhibits different expression profiles in different types of cancer (11)(12)(13)(15)(16)(17)(18). Upregulation of miR-20a has been found in GBC (13), colon adenocarcinoma (15) and gliomas (16), while miR-20a down- regulation has been reported in primary HCC (11), OSCC (12), breast cancer (17) and pancreatic carcinoma (18).…”

“…Upregulation of miR-20a has been found in GBC (13), colon adenocarcinoma (15) and gliomas (16), while miR-20a down- regulation has been reported in primary HCC (11), OSCC (12), breast cancer (17) and pancreatic carcinoma (18). This suggests that the function of miR-20a may vary among different types of tumor.…”

“…miR-20a has been reported to be associated with EMT in various types of cancers. In hepatocellular carcinoma (HCC), miR-20a restoration has been shown to inhibit cell proliferation and induce apoptosis by targeting the 3'-UTR of Mcl-1, while decreased expression of miR-20a has been reported to correlate significantly with the aggressive characteristics of HCC cells (11). In addition, the upregulated expression of miR-20a has been found to decrease the migratory ability of oral squamous cell carcinoma (OSCC) cell lines (12), and the ectopic expression of miR-20a has been demonstrated to induce the EMT and enhance the metastasis of gallbladder carcinoma (GBC) cells in vitro and in vivo (13).…”

MicroRNA screening identifies circulating microRNAs as potential biomarkers for osteosarcoma

“…miR-106a was previously shown to be downregulated in glioma, colon cancer, squamous cell carcinoma and astrocytoma, and functions as a tumor suppressor by targeting solute carrier family 2 (facilitated glucose transporter), member 3 (33), E2F transcription factor 1 (34) and Fas-activated serine/threonine kinase (35). Similarly, miR-20a is downregulated in hepatocellular carcinoma (HCC) and correlated with HCC recurrence and poor prognosis (36). In addition, miR-425 is able to reduce proliferation, impair tumorigenesis and metastasis, and increase expression of epithelial markers in aggressive breast cancer cells by targeting SATB homeobox 1, CCND2 and Fascin actin-bundling protein 1 (37).…”

Pleomorphic adenoma gene 1 mediates the role of Karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma

“…The survival of HCC patients after resection remains poor, mainly attributing to frequent metastases and recurrence [2]. Recently, plenty of researches have performed to explore mechanisms underlying the initiation, propagation and development of HCC [3,4]. However, the complexity of HCC need further hypothesis-drove researches to be exerted.…”