Abstract
MicroRNAs have been broadly implicated in cancer, but precise functions and mechanisms in carcinogenesis vary among cancer types and in many cases remain poorly understood. Hepatocellular carcinoma (HCC) is among the most frequent and lethal cancers. The aim of the present study was to investigate the role of miR-486-5p in HCC and identify its specific target. MiR-486-5p was significantly downregulated in HCC tissues and cell lines compared with noncancerous tissues and, respectively, although expression level was not correlated with the degree of infiltration or tumor stage. However, miR-486-5p overexpression in HCC cells inhibited proliferation and migration as evidenced by CCK-8 cell counting, wound healing, and transwell assays, indicating that miR-486-5p is an HCC suppressor. We employed four miRNA databases to predict the target genes of miR-486-5p and verified retrieved genes using qPCR and western blotting. The E3 ubiquitin ligase CBL was significantly downregulated by miR-486-5p overexpression in HCC cell lines at both mRNA and protein level, and overexpression of CBL counteracted the inhibitory effects of miR-486-5p on HCC cell proliferation and migration. Moreover, CBL expression was negatively correlated with miR-486-5p expression in HCC tissues. Collectively, our results suggest that miR-486-5p may act as a tumor suppressor gene in HCC by downregulating CBL expression.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancerrelated mortality [1]
The overall survival rate of HCC patients has increased in recent years, metastasis and recurrence are still common
We demonstrate that miR-486-5p inhibits the proliferation and migration of HCC cells, at least in part by downregulating expression and activity of the E3 ubiquitin ligase CBL
Summary
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancerrelated mortality [1]. Improvements in diagnostic techniques have increased early detection and decreased mortality over the past decade, the incidence of HCC continues to increase and overall outcomes remain poor, with 5-year overall survival (OS) rate of only 3%–5% [2]. Evidence is accumulating that miRNAs are dysregulated in various human cancers, including HCC. Ese dysregulated miRNAs are often involved in processes relevant to tumorigenesis, tumor growth, and metastasis, such as cell proliferation, apoptosis, angiogenesis, and migration, thereby acting as oncogenes or tumor suppressors [4,5,6,7]. It has been reported that miR-486 relieves particulate matter-induced injury of human lung alveolar epithelial A549 cells by targeting PTEN and FOXO1 [8]. The biological functions and downstream targets of miR-486-5p in HCC have remained elusive
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