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.
Highlights
Hepatocellular carcinoma (HCC) is one of the leading causes for tumor-related mortalities worldwide [1]
Lowered miR-517c Expressions in HCC Correlated with the Malignant Phenotypes of HCC Patients. miR-517c expressions in HCC tissues and cells were measured by qRTPCR. e results indicated that that miR-517c was significantly downregulated in HCC tissues (Figure 1(a))
The decreased miR-517c expression was identified in HCC cells (Figure 1(b))
Summary
Hepatocellular carcinoma (HCC) is one of the leading causes for tumor-related mortalities worldwide [1]. Deterioration of the original tumor, metastasis, and relapse have been identified as common factors for the high mortality rates of patients with HCC [2]. E current treatment strategies for HCC patients are mainly liver transplantation and tumor resection. Advanced diagnoses of HCC patients are very common, and lacking specific biomarkers as well as high metastasis rates in advanced stages made tumor resection impracticable; as a result, only a few HCC patients are suitable for surgery [3, 4]. Erefore, it is emergent to unravel the mechanism of HCC metastasis and recurrence, to explore promising therapeutic approaches for HCC treatments. Recent studies have indicated that dysregulated miRs in HCC could be used as promising therapeutic and diagnostic targets [9]. Recent studies have indicated that dysregulated miRs in HCC could be used as promising therapeutic and diagnostic targets [9]. erefore, it is Journal of Healthcare Engineering imperative to characterize novel miRs which participated in HCC metastasis and tumorigenesis, providing novel insights into HCC diagnosis, therapies, and prognosis
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