miRNA-217 inhibits proliferation of hepatocellular carcinoma cells by regulating KLF5.

OBJECTIVE

The aim of this study was to figure out the effect of microRNA-217 on the proliferation of hepatocellular carcinoma (HCC) cells, and to explore its influence on KLF5 expression and the underlying regulatory mechanisms.

PATIENTS AND METHODS

Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-217 in tumor tissues and paracancerous tissues of 60 patients with HCC. Meanwhile, the relationship between microRNA-217 expression and HCC pathological parameters was analyzed. In HCC cell lines, including HepG2 and Bel-7402, negative control group (NC) and microRNA-217 overexpression group were set up, and qRT-PCR was performed to further verify their transfection efficiency. In addition, Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay were performed to analyze the effect of microRNA-217 on the biological function of HCC cells. Finally, the potential mechanism of KLF5, the downstream gene of microRNA-217, was explored using bioinformatics analysis and cell recovery experiments.

RESULTS

QRT-PCR results showed that microRNA-217 level in tumor tissues of HCC patients was conspicuously lower than that in adjacent tissues, and the difference was statistically significant. Compared with patients with high expression of microRNA-217, the pathological stage was higher and the overall survival rate was lower in patients with low expression. Compared with the NC group, the cell proliferation ability of the microRNA-217 mimics group was conspicuously decreased. Subsequently, in the HCC cell line and tissue verification, the expression of KLF5 was found remarkably increased, and microRNA-217 exhibited a negative correlation with KLF5 level. In addition, the overexpression of microRNA-217 conspicuously reduced the protein expression of CD31, Ki-67, c-Myc, MMP-2, and MMP-9. In cell recovery experiment, it was found that the overexpression of KLF5 could counteract the effect of microRNA-217 mimics on the cell proliferation of HCC, thereby inhibiting the malignant progression of this disease.

CONCLUSIONS

The above studies demonstrated that microRNA-217 was markedly associated with the pathological stage and poor prognosis of HCC, and could inhibit the malignant progression of this disease. In addition, our investigation has showed that microRNA-217 might be capable of inhibiting cell proliferation of HCC via regulating KLF5.