ABSTRACT
OBJECTIVE: Hepatocellular carcinoma (HCC) is a kind of solid and highly aggressive malignant tumor with poor prognosis. MicroRNA (miRNA/miR) has been confirmed to be involved in HCC development. The current study focused on the functions and mechanisms of miR-517c in HCC. METHODS: Expressions of miR-517c and Karyopherin α2 (KPNA2) mRNA in HCC cell lines and tissue samples were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was conducted for detections of epithelial-to-mesenchymal transition (EMT) and PI3K/AKT markers. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell assays were utilized to investigate the influence of miR-517c on HCC cell proliferation, invasion, and migration. TargetScan and luciferase reporter assay were performed to search for the potential target gene of miR-517c. RESULTS: We demonstrated that miR-517c expressions were decreased in HCC tissues and cells. Moreover, the clinical analysis showed that decreased miR-517c expressions in HCC tissues correlated with shorter overall survival and malignant clinicopathologic features of HCC patients. MTT assay showed that miR-517c upregulation prominently repressed HCC cell proliferation. In addition, miR-517c restoration could significantly suppress HCC cell invasion and migration as demonstrated by Transwell assays. We also found that miR-517c directly targeted KPNA2 and regulated the PI3K/AKT pathway and EMT, exerting prohibitory functions in HCC. CONCLUSION: Taken together, this study stated that miR-517c inhibited HCC progression via regulating the PI3K/AKT pathway and EMT and targeting KPNA2 in HCC, providing a novel insight into HCC treatment.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Down-Regulation , Humans , Liver Neoplasms/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , alpha Karyopherins/genetics , alpha Karyopherins/metabolismABSTRACT
Liver cancer is a malignant tumor that threatens human health worldwide. It has poor prognosis rates and ineffective therapeutic options. Recently, various miRNAs have been proven to exert promoting or inhibiting functions in different malignancies. However, the definitive mechanisms of miR-99a in liver cancer remain unclear. In the current study, we explored the relationships between the expression of miR-99a and HOXA1 in liver cancer tissues and cells to explore their combined effects on the occurrence and metastasis of liver cancer. The expression of miR-99a and HOXA1 in liver cancer tissue samples and cells was measured by RT-qPCR. Following transfection, transwell assays were conducted to assess the invasion and migration capacities of liver cancer cells. Subsequently, western blots and luciferase reporter assays were performed in liver cancer cells to identify the target of miR-99a. The data indicated that miRNA-99a expression was significantly reduced in both liver cancer tissue samples and cells compared with normal tissues and normal liver cells respectively. By contrast, the HOXA1 expression levels in liver cancer tissues and cells were significantly increased in contrast to the control group. The findings also revealed that the miR-99a expression was negatively correlated with HOXA1 expression in liver cancer tissue samples and miR-99a could suppress cell invasion and migration by targeting HOXA1 in liver cancer.
