Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2
Open Access
- 14 May 2015
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Hematology & Oncology
- Vol. 8 (1), 57-14
- https://doi.org/10.1186/s13045-015-0146-0
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, especially in China. And the mechanism of its progression remains poorly understood. Growing evidence indicates that long non-coding RNAs (lncRNAs) are found to be dysregulated in many cancers, including HCC. CDKN2B antisense RNA1 (ANRIL), a lncRNA, coclustered mainly with p14/ARF has been reported to be dysregulated in gastric cancer, esophageal squamous cell carcinoma, and lung cancer. However, its clinical significance and potential role in HCC is still not documented. In this study, expression of ANRIL was analyzed in 77 HCC tissues and matched normal tissues by using quantitative real-time polymerase chain reaction (qRT-PCR). ANRIL expression was up-regulated in HCC tissues, and the higher expression of ANRIL was significantly correlated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage. Moreover, taking advantage of loss of function experiments in HCC cells, we found that knockdown of ANRIL expression could impair cell proliferation and invasion and induce cell apoptosis both in vitro and in vivo. We also found that ANRIL could epigenetically repress KLF2 transcription in HCC cells by binding with PRC2 and recruiting it to KLF2 promoter region. We also found that Sp1 could regulate the expression of ANRIL. Our results suggest that lncRNA ANRIL, as a growth regulator, may serve as a new biomarker and target for therapy in HCC.Keywords
This publication has 35 references indexed in Scilit:
- p53-dependent Induction of PVT1 and miR-1204Published by Elsevier BV ,2012
- Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15INK4B tumor suppressor geneOncogene, 2010
- Long Noncoding RNA as Modular Scaffold of Histone Modification ComplexesScience, 2010
- ANRIL is implicated in the regulation of nucleus and potential transcriptional target of E2F1Oncology Reports, 2010
- Molecular Interplay of the Noncoding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4aMolecular Cell, 2010
- Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasisNature, 2010
- Long noncoding RNAs: functional surprises from the RNA worldGenes & Development, 2009
- Transcription factor ELF4 controls the proliferation and homing of CD8+ T cells via the Krüppel-like factors KLF4 and KLF2Nature Immunology, 2009
- Evolution and Functions of Long Noncoding RNAsCell, 2009
- Applied bioinformatics for the identification of regulatory elementsNature Reviews Genetics, 2004