Purpose: Hepatocellular carcinoma (HCC) has the fourth highest rate of mortality among the different types of cancer worldwide. This study aimed to investigate the functions of microRNA-145-5p and AFR6 on migration, invasion and metastasis in HCC.
Methods: A total of 150 pairs of tumor and their matched adjacent nontumor liver tissues were collected from HCC patients. Expressions of microRNA-145-5p and AFR6 were measured by real-time PCR in HCC tissues and in HCC cell lines. The correlations between microRNA-145-5p and HCC prognosis were investigated. The proliferation, migration, invasion, cell cycle progression, and apoptosis of HCCLM3 cells were evaluated with CCK8, wound healing, transwell, and flow cytometric experiments.
Results: The expression of miR-145-5p was confirmed to be downregulated not only in HCC tissues but also in several HCC cell lines compared with normal controls. A low expression level of miR-145-5p was notably associated with poor prognosis in patients with HCC and certain characteristics of metastatic tumors. In vitro, miR-145-5p negatively regulated cell proliferation, migration, and invasion and induced apoptosis in HCCLM3 cells. Subsequent experiments further verified that ARF6 is a novel target of miR-145-5p and is significantly overexpressed in HCC tissues. Overexpression of ARF6 circumvented the effects of miR-145-5p in HCCLM3 cells.
Conclusion: miR-145-5p may play a pivotal role in HCC metastasis via regulating ARF6, and these findings may both provide further insights into the key factors of HCC metastasis and prove to be useful in the development of novel treatment options for HCC.
Keywords: microRNA-145-5p, ADP-ribosylation factor 6, hepatocellular carcinoma, proliferation, invasion, metastasis