EGR1 诱导的长链非编码 RNA FOXD2-AS1 上调促进肝细胞癌的进展，通过表观遗传沉默 DKK1 并激活 Wnt/β-catenin 信号通路。
EGR1-induced upregulation of lncRNA FOXD2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating Wnt/β-catenin signaling pathway.
机构信息
a Department of hepatobiliary and pancreatic surgery , Luoyang Central Hospital, affiliated with Zhengzhou University , Luoyang city , Henan Province China.
b Department of liver surgery and Transplantation , Liver Cancer Institute, Zhongshan Hospital, Fudan University , Shanghai China.
出版信息
Cancer Biol Ther. 2019;20(7):1007-1016. doi: 10.1080/15384047.2019.1595276. Epub 2019 Mar 31.
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.
长链非编码 RNA（lncRNAs）被认为是多种癌症（包括肝细胞癌（HCC））发生和发展的一组生物标志物。lncRNA FOXD2-AS1 已在人类结直肠癌和神经胶质瘤中作为癌基因进行了研究。然而，lncRNA FOXD2-AS1 在肝细胞癌中的功能和机制尚不清楚。在本研究中，我们发现 TCGA 数据库中 FOXD2-AS1 高表达预示着 HCC 患者预后不良。通过 qRT-PCR 确定了 HCC 组织和细胞系中 FOXD2-AS1 的失调。功能上，沉默 FOXD2-AS1 通过调节细胞增殖、凋亡、迁移和上皮-间充质转化（EMT）有效地抑制 HCC 进展。机制上，发现 FOXD2-AS1 被转录因子 EGR1 激活。此外，FOXD2-AS1 可以激活 Wnt/β-catenin 信号通路。分析了 FOXD2-AS1 与 Wnt/β-catenin 信号通路相互作用的机制。发现 FOXD2-AS1 通过表观遗传沉默 Wnt/β-catenin 信号通路抑制剂（DKK1）来增强 Wnt/β-catenin 信号通路的活性。挽救实验表明，DKK1 和 Wnt/β-catenin 信号通路参与了 FOXD2-AS1 介导的 HCC 进展。总之，我们的研究表明，EGR1 诱导的长链非编码 RNA FOXD2-AS1 的上调通过表观遗传沉默 DKK1 和激活 Wnt/β-catenin 信号通路促进肝细胞癌的进展。
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