Overexpression of miR-664 is associated with poor overall survival and accelerates cell proliferation, migration and invasion in hepatocellular carcinoma.

INTRODUCTION

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. This study aimed to investigate the expression patterns of microRNA-664 (miR-664) in HCC tissues and cells, and assess its clinical significance and functional role in HCC.

PATIENTS AND METHODS

One hundred and thirty-four paired HCC and non-cancerous tissues were collected from patients who underwent surgery in Qianfoshan Hospital affiliated to Shandong University (Shandong, China) between 2009 and 2012. Expression of miR-664 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Prognostic value of miR-664 in HCC was evaluated using Kaplan-Meier survival analysis and Cox regression analysis. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion of HCC cells was evaluated by the Transwell assay.

RESULTS

Expression of miR-664 was significantly upregulated in HCC tissues and cells when compared with the normal controls (all <0.05). MiR-664 expression was associated with lymph node metastasis, TNM stage and differentiation (all <0.05) in the HCC patients. High miR-664 expression predicted poor overall survival (log-rank =0.004) and acted as an independent prognostic factor (HR =1.945, 95% CI=1.078-3.508, =0.027). According to cell experiments, the upregulation of miR-664 could promote, whereas the downregulation of miR-664 could inhibit proliferation, migration and invasion of HCC cells (all <0.05). SIVA1 was predicted as a direct target gene of miR-664 in HCC.

CONCLUSION

All data indicated that overexpression of miR-664 is associated with poor prognosis of HCC patients, and may enhance tumor progression of HCC by targeting SIVA1. MiR-664 may be a candidate therapeutic target for HCC treatment.