Objective: Yes-associated protein (Yes-associated protein 1 [YAP1]) is an important oncogene that is related to the pathogenesis and progression of liver cancer. It was found that miR-424-5p expression was significantly decreased in liver cancer tissues, revealing its anticancer effect. Bioinformatic analysis demonstrated the targeted relationship between miR-424-5p and the 3' untranslated region of YAP1. This study investigated the role of miR-424-5p in regulating YAP1 expression and affecting hepatoma cell proliferation and apoptosis.
Materials and methods: Tumors and normal liver tissues adjacent to tumors were collected from patients to detect the expression of miR-424-5p and YAP1. A dual-luciferase reporter gene assay was adopted to explore the targeted regulation between miR-424-5p and YAP1. Liver cancer HCCLM3 and MHCC97-L cells and normal liver HL-7702 cells were cultured in vitro to compare expression levels of miR-424-5p and YAP1. HCCLM3 and MHCC97-L cells were divided into the miR-NC group and miR-424-5p mimic group. Cell apoptosis was detected by flow cytometry. Cell proliferation was determined by EdU staining.
Results: Compared with normal liver tissue, miR-424-5p expression was significantly decreased, while YAP1 mRNA and protein levels were obviously upregulated in liver cancer tissues, which were related to the clinical stage. A negative correlation was found between miR-424-5p and YAP1 mRNA levels in liver cancer tissues. Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-424-5p and YAP1. miR-424-5p expression in HCCLM3 and MHCC97-L cells decreased compared with L20 cells, which correlated with malignancy. YAP1 level in HCCLM3 and MHCC97-L cells was significantly enhanced, which correlated with malignancy. miR-424-5p mimic transfection significantly downregulated YAP1 expression in HCCLM3 and MHCC97-L cells, resulting in enhanced apoptosis and attenuated cell proliferation.
Conclusions: Decreased miR-424-5p expression and increased YAP1 expression are found in patients with liver cancer. Increased miR-424-5p can inhibit YAP1 expression, attenuate hepatoma cell proliferation, and induce cell apoptosis.
Keywords: YAP1; apoptosis; liver cancer; miR-424-5p; proliferation.