CAF-related miR-642a-3p supports the migration, invasion, and EMT of hepatocellular carcinoma by targeting SERPINE1

Abstract

Abstract Hepatocellular carcinoma (HCC) is one of the most deadly malignancies. Due to the late detection of HCC, the treatment are not satisfactory, accompanied by poor prognosis. Therefore, early detection has important value for HCC treatment. MicroRNAs (miRNAs), the intercellular communication in the tumor microenvironment, are widely accepted as molecular markers of HCC. However, there are few studies on miRNAs involved in the crosstalk between cancer-associated fibroblast (CAF) and HCC cells. In the study, transcriptome sequencing, siRNA, co-culture, reverse transcription quantitative real-time PCR (RT-qPCR), western blot, dual-luciferase reporter system, and xenograft tumor model, were used to explore the role of miR-642a-3p/SERPINE1 axis in HCC progression. The results showed that in co-culture with CAF, the expression of SERPINE1 mRNA decreased, whereas miR-642a-3p expression increased in Huh7 cells. SERPINE1 knockdown significantly enhanced the invasion ability and increased miR-642a-3p expression in Huh7 cells. Dual-luciferase reporter assay discovered that miR-642a-3p had a binding effect with SERPINE1, suggesting that SERPINE1 was a target of miR-642a-3p. In addition, miR-642a-3p mimics inhibited SERPINE1 expression and promoted the migration, invasion, and EMT of Huh7 cells, whereas miR-642a-3p inhibitor had the opposite effect. More importantly, miR-642a-3p knockdown inhibited the proliferation and spread of xenograft tumors in the liver. miR-642a-3p knockdown significantly inhibited epithelial-mesenchymal transition (EMT) in the liver. These findings reveal that the miR-642a-3p/SERPINE1 axis plays an important role in the invasion and metastasis of HCC, and can be used as a novel therapeutic target for HCC.