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Published on: December 13, 2018
Long noncoding RNA ANRIL promotes the malignant progression of cholangiocarcinoma by epigenetically repressing ERRFI1
Yang Yu1, Qiaoyu Chen2, Xunlei Zhang1
1Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, China.
Abstract:
Long noncoding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many types of human cancers. The lncRNA ANRIL is transcribed from the INK4b-ARF-INK4a gene cluster in the opposite direction. Whether ANRIL can act as an oncogenic molecule in cholangiocarcinoma (CCA) remains unknown. Our data show that ANRIL knockdown greatly inhibited CCA cell proliferation and migration in vitro and in vivo. According to the results of RNA sequencing analysis, ANRIL knockdown dramatically altered target genes associated with the cell cycle, cell proliferation, and apoptosis. By binding to a component of the epigenetic modification complex enhancer of zeste homolog 2 (EZH2), ANRIL could maintain lysine residue 27 of histone 3 (H3K27me3) levels in the promoter of ERBB receptor feedback inhibitor 1 (ERRFI1), which is a tumor suppressor gene in CCA. In this way, ERRFI1 expression was suppressed in CCA cells. These data verified the key role of the epigenetic regulation of ANRIL in CCA oncogenesis and indicate its potential as a target for CCA intervention.
Insights
The long noncoding RNA ANRIL promotes cholangiocarcinoma (CCA) by epigenetically silencing the tumor suppressor ERRFI1. Inhibiting ANRIL suppressed CCA cell growth and migration, suggesting ANRIL as a therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Epigenetics
Background:
- Long noncoding RNAs (lncRNAs) play crucial roles in human cancers.
- The lncRNA ANRIL's function in cholangiocarcinoma (CCA) is currently unknown.
Purpose of the Study:
- To investigate the role of ANRIL in cholangiocarcinoma (CCA) development.
- To explore ANRIL's potential as a therapeutic target for CCA.
Main Methods:
- RNA sequencing analysis was performed after ANRIL knockdown.
- The interaction between ANRIL, EZH2, and the ERRFI1 promoter was investigated.
- Cell proliferation and migration assays were conducted in vitro and in vivo.
Main Results:
- ANRIL knockdown significantly inhibited CCA cell proliferation and migration.
- ANRIL epigenetically suppresses the tumor suppressor gene ERRFI1 by interacting with EZH2 and maintaining H3K27me3 levels.
- RNA sequencing revealed ANRIL knockdown altered genes involved in cell cycle, proliferation, and apoptosis.
Conclusions:
- ANRIL acts as an oncogenic molecule in CCA through epigenetic regulation.
- ANRIL is a potential therapeutic target for cholangiocarcinoma intervention.
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