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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2015

Open Access 01-12-2015 | Research article

Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2

Authors: Ming-de Huang, Wen-ming Chen, Fu-zhen Qi, Rui Xia, Ming Sun, Tong-peng Xu, Li Yin, Er-bao Zhang, Wei De, Yong-qian Shu

Published in: Journal of Hematology & Oncology | Issue 1/2015

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Abstract

Background

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. ANRIL, a lncRNA co-clustered 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 are still not documented.

Methods and results

In this study, expression of ANRIL was analyzed in 77 HCC tissues and matched normal tissues by using quantitative polymerase chain reaction (qRT-PCR). ANRIL expression was upregulated 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 Kruppel-like factor 2 (KLF2) transcription in HCC cells by binding with PRC2 and recruiting it to the KLF2 promoter region. We also found that SP1 could regulate the expression of ANRIL.

Conclusion

Our results suggest that lncRNA ANRIL, as a growth regulator, may serve as a new biomarker and target for therapy in HCC.
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Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics. CA Cancer J Clin. 2012;2015(65):87–108.
2.
3.
4.
5.
Chakravarty D, Sboner A, Nair SS, Giannopoulou E, Li R, Hennig S, et al. The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nat Commun. 2014;5:5383.CrossRefPubMedPubMedCentral
6.
Yacqub-Usman K, Pickard MR, Williams GT. Reciprocal regulation of GAS5 lncRNA levels and mTOR inhibitor action in prostate cancer cells. Prostate. 2015;75:693–705.CrossRefPubMed
7.
Xu TP, Huang MD, Xia R, Liu XX, Sun M, Yin L, et al. Decreased expression of the long non-coding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression. J Hematol Oncol. 2014;7:63.CrossRefPubMedPubMedCentral
8.
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentral
9.
Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long non-coding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71:6320–6.CrossRefPubMed
10.
Yap KL, Li S, Munoz-Cabello AM, Raguz S, Zeng L, Mujtaba S. Molecular interplay of the non-coding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell. 2010;38:662–74.CrossRefPubMedPubMedCentral
11.
Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D, Bieche I. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense non-coding RNA whose expression coclusters with ARF. Cancer Res. 2007;67:3963–9.CrossRefPubMed
12.
Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, et al. Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15 (INK4B) tumor suppressor gene. Oncogene. 2011;30:1956–62.CrossRefPubMed
13.
Wan G, Mathur R, Hu X, Liu Y, Zhang X, Peng G, et al. Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway. Cell Signal. 2013;25:1086–95.CrossRefPubMedPubMedCentral
14.
Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, et al. Long non-coding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a. Oncotarget. 2014;5:2276–92.CrossRefPubMedPubMedCentral
15.
Nie FQ, Sun M, Yang JS, Xie M, Xu TP, Xia R, et al. Long non-coding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther. 2015;14:268–77.CrossRefPubMed
16.
Ponting CP, Oliver PL, Reik W. Evolution and functions of long non-coding RNAs. Cell. 2009;136:629–41.CrossRefPubMed
17.
Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long non-coding RNA as modular scaffold of histone modification complexes. Science. 2010;329:689–93.CrossRefPubMedPubMedCentral
18.
19.
Sun M, Liu XH, Wang KM, Nie FQ, Kong R, Yang JS, et al. Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition. Mol Cancer. 2014;13:68.CrossRefPubMedPubMedCentral
20.
Hirata H, Hinoda Y, Shahryari V, Deng G, Nakajima K, Tabatabai ZL, et al. Long non-coding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res. 2015;75:1322–31.CrossRefPubMed
21.
Cui M, Xiao Z, Wang Y, Zheng M, Song T, Cai X, et al. Long non-coding RNA HULC modulates abnormal lipid metabolism in hepatoma cells through an miR-9-mediated RXRA signaling pathway. Cancer Res. 2015;75:846–57.CrossRefPubMed
22.
Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as non-coding RNA. Gastroenterology. 2007;132:330–42.CrossRefPubMed
23.
Yuan SX, Yang F, Yang Y, Tao QF, Zhang J, Huang G, et al. Long non-coding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology. 2012;56:2231–41.CrossRefPubMed
24.
Xu WH, Zhang JB, Dang Z, Li X, Zhou T, Liu J, et al. Long non-coding RNA URHC regulates cell proliferation and apoptosis via ZAK through the ERK/MAPK signaling pathway in hepatocellular carcinoma. Int J Biol Sci. 2014;10:664–76.CrossRefPubMedPubMedCentral
25.
Ma MZ, Li CX, Zhang Y, Weng MZ, Zhang MD, Qin YY, et al. Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer. Mol Cancer. 2014;13:156.CrossRefPubMedPubMedCentral
26.
Barsotti AM, Beckerman R, Laptenko O, Huppi K, Caplen NJ, Prives C. p53-Dependent induction of PVT1 and miR-1204. J Biol Chem. 2012;287:2509–19.CrossRefPubMed
27.
Sato K, Nakagawa H, Tajima A, Yoshida K, Inoue I. ANRIL is implicated in the regulation of nucleus and potential transcriptional target of E2F1. Oncol Rep. 2010;24:701–7.PubMed
28.
Black AR, Black JD, Azizkhan-Clifford J. Sp1 and Kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol. 2001;188:143–60.CrossRefPubMed
29.
30.
Ebert R, Zeck S, Meissner-Weigl J, Klotz B, Rachner TD, Benad P, et al. Kruppel-like factors KLF2 and 6 and Ki-67 are direct targets of zoledronic acid in MCF-7 cells. Bone. 2012;50:723–32.CrossRefPubMed
31.
Yamada T, Park CS, Mamonkin M, Lacorazza HD. Transcription factor ELF4 controls the proliferation and homing of CD8+ T cells via the Kruppel-like factors KLF4 and KLF2. Nat Immunol. 2009;10:618–26.CrossRefPubMedPubMedCentral
32.
Wong JC, Guo L, Peng Z, Zhang W, Zhang N, Lai W, et al. Application of p21 and klf2 reporter gene assays to identify selective histone deacetylase inhibitors for cancer therapy. Bioorg Med Chem Lett. 2011;21:110–6.CrossRefPubMed
33.
Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–38.CrossRefPubMed
34.
Wasserman WW, Sandelin A. Applied bioinformatics for the identification of regulatory elements. Nat Rev Genet. 2004;5:276.CrossRefPubMed
Metadata
Title
Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2
Authors
Ming-de Huang
Wen-ming Chen
Fu-zhen Qi
Rui Xia
Ming Sun
Tong-peng Xu
Li Yin
Er-bao Zhang
Wei De
Yong-qian Shu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-015-0146-0

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