EGR1-induced upregulation of lncRNA FOXD2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating Wnt/β-catenin signaling pathway

Abstract

Long non-coding RNAs (lncRNAs) are regarded as a group of biomarkers in the initiation and development of various cancers, including hepatocellular carcinoma (HCC). LncRNA FOXD2-AS1 has been studied in human colorectal cancer and glioma as an oncogene. However, the function and mechanism of lncRNA FOXD2-AS1 in hepatocellular carcinoma are marked. In this study, we found that high expression of FOXD2-AS1 predicted poor prognosis of HCC patients in the TCGA database. The dysregulation of FOXD2-AS1 was determined in HCC tissues and cell lines by qRT-PCR. Functionally, silenced FOXD2-AS1 efficiently suppressed HCC progression by regulating cell proliferation, apoptosis, migration and epithelial–mesenchymal transition (EMT). Mechanistically, FOXD2-AS1 was found to be activated by the transcription factor EGR1. Furthermore, FOXD2-AS1 could activate the Wnt/β-catenin signaling pathway. The mechanism contributed to the interaction between FOXD2-AS1 and Wnt/β-catenin signaling pathway was analyzed. It was uncovered that FOXD2-AS1 enhanced the activity of Wnt/β-catenin signaling pathway by epigenetically silencing the inhibitor of Wnt/β-catenin signaling pathway (DKK1). Rescue assays demonstrated that DKK1 and Wnt/β-catenin signaling pathway involved in FOXD2-AS1-mediated HCC progression. In conclusion, our study demonstrated that EGR1-induced upregulation of lncRNA FOXD2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating Wnt/β-catenin signaling pathway.