Dataset Information

EGR1-induced upregulation of lncRNA FOXD2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating Wnt/?-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/?-catenin signaling pathway. The mechanism contributed to the interaction between FOXD2-AS1 and Wnt/?-catenin signaling pathway was analyzed. It was uncovered that FOXD2-AS1 enhanced the activity of Wnt/?-catenin signaling pathway by epigenetically silencing the inhibitor of Wnt/?-catenin signaling pathway (DKK1). Rescue assays demonstrated that DKK1 and Wnt/?-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/?-catenin signaling pathway.

SUBMITTER: Lei T

PROVIDER: S-EPMC6606006 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Lei Ting T Zhu Xiaodong X Zhu Kai K Jia Fuxin F Li Siqiao S

Cancer biology & therapy 20190331 7

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 ...[more]

PMID: 30929558

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Project description:BackgroundLong non-coding RNAs (lncRNAs) are pervasively transcribed in genome and emerging as a new player in tumorigenesis due to their functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. As the most frequent malignancy and the foremost source of cancer mortality, lung cancer is a heterogeneous disorder. The most common type of lung cancer is Non-small cell lung cancer (NSCLC), occupying 85% of the total cases, and the main subtypes of NSCLC include lung adenocarcinoma (LAD), large cell carcinoma (LCC), and lung squamous cell carcinoma (LSCC). Recently, numerous lncRNAs have been reported to be strongly linked to NSCLC. In the present study, we found that a new lncRNA CBR3-AS1 is highly expressed in lung cancer. In addition, we also examined the expression of lncRNA CBR3-AS1 in 60 of LADs, 40 of LCCs and 40 of LSCCs patient samples, finding that CBR3-AS1 was specificity highly expressed in LAD cancer tissues. Mechanically, we discovered that CBR3-AS1 could regulate the proliferation, migration and invasion of LAD cells through targeting Wnt/β-catenin signaling.MethodsReal-time PCR, RNA-pulldown, RIP, western blotting, lentivirus transfection, luciferase reporter assays, cell proliferation assays, colony formation assays, wound healing scratch assays and transwell assays were employed to examine the relationship between lncRNA CBR3-AS1 and its regulation of Wnt/β-catenin signaling in LAD cells.ResultsLncRNA CBR3-AS1 is highly-expressed in LAD and cell lines. LncRNA CBR3-AS1 shows physical association with β-catenin. CBR3-AS1 could facilitate Wnt/β-catenin signaling activation thought promoting nuclear localization of β-catenin. CBR3-AS1 promotes LAD cell proliferation, migration and invasion by targeting Wnt/β-catenin signaling.ConclusionIt can be found that a new functional lncRNA CBR3-AS1 could promote nuclear localization of β-catenin so as to facilitate Wnt/β-catenin signaling activation and regulate the proliferation, migration and invasion of LAD cells.

Dataset Information

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

Publications

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

Similar Datasets

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