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

被引：41
作者：
Lei, Ting [1 ]
Zhu, Xiaodong [2 ]
Zhu, Kai [2 ]
Jia, Fuxin [1 ]
Li, Siqiao [1 ]
机构：
[1] Zhengzhou Univ, Luoyang Cent Hosp, Dept Hepatobiliary & Pancreat Surg, Luoyang City, Henan, Peoples R China
[2] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg & Transplantat, 180 Fenglin Rd, Shanghai 200032, Peoples R China
来源：
CANCER BIOLOGY & THERAPY | 2019年 / 20卷 / 07期
关键词：
FOXD2-AS1; EGR1; proliferation; migration; hepatocellular carcinoma; Wnt/beta-catenin signaling pathway; EPITHELIAL-MESENCHYMAL TRANSITION; COLORECTAL-CANCER PROGRESSION; LONG NONCODING RNAS; CELL-PROLIFERATION; DOWN-REGULATION; INVASION; EXPRESSION; MIGRATION; METASTASIS; KNOCKDOWN;
D O I：
10.1080/15384047.2019.1595276
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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/beta-catenin signaling pathway. The mechanism contributed to the interaction between FOXD2-AS1 and Wnt/beta-catenin signaling pathway was analyzed. It was uncovered that FOXD2-AS1 enhanced the activity of Wnt/beta-catenin signaling pathway by epigenetically silencing the inhibitor of Wnt/beta-catenin signaling pathway (DKK1). Rescue assays demonstrated that DKK1 and Wnt/beta-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/beta-catenin signaling pathway.
引用
收藏
页码：1007 / 1016
页数：10
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