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Article

Truncated Isoforms of lncRNA ANRIL Are Overexpressed in Bladder Cancer, But Do Not Contribute to Repression of INK4 Tumor Suppressors

by
Michèle J. Hoffmann
1,*,
Judith Dehn
1,
Johanna Droop
1,
Günter Niegisch
1,
Christian Niedworok
2,
Tibor Szarvas
2,3 and
Wolfgang A. Schulz
1
1
Department of Urology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany; Moorenstrasse 5, Düsseldorf 40225, Germany
2
Department of Urology, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany
3
Department of Urology, Semmelweis University, Ülloi ut 78/b, 1082 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Non-Coding RNA 2015, 1(3), 266-284; https://doi.org/10.3390/ncrna1030266
Submission received: 25 August 2015 / Revised: 6 December 2015 / Accepted: 8 December 2015 / Published: 17 December 2015
(This article belongs to the Section Long Non-Coding RNA)
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Abstract

The INK4/ARF locus at chromosome 9p21 encoding p14ARF, p15INK4B and p16INK4A is a major tumor suppressor locus, constituting an important barrier for tumor growth. It is frequently inactivated in cancers, especially in urothelial carcinoma (UC). In addition to deletions and DNA hypermethylation, further epigenetic mechanisms might underlie its repression. One candidate factor is the long noncoding RNA ANRIL, which recruits Polycomb proteins (PcG) to regulate expression of target genes in cis and trans. We observed ANRIL overexpression in many UC tissues and cell lines mainly resulting from upregulation of 3’-truncated isoforms. However, aberrant ANRIL expression was neither associated with repression of INK4/ARF genes nor with proliferation activity or senescence. We wondered whether truncated ANRIL isoforms exhibit altered properties resulting in loss of function in cis. We excluded delocalization and performed RNA immunoprecipitation demonstrating interaction between full length or truncated ANRIL and PcG protein CBX7, but not SUZ12 of PRC2. Our data indicate that ANRIL in UC cells may not interact with PRC2, which is central for initializing gene repression. Thus, tissue-specific binding activities between ANRIL and PcG proteins may determine the regulatory function of ANRIL. In conclusion, ANRIL does not play a major role in repression of the INK4/ARF locus in UC.
Keywords: long noncoding RNA; ANRIL; p16; p14; p15; INK4/ARF; tumor suppressor; polycomb; bladder cancer; PVT1 long noncoding RNA; ANRIL; p16; p14; p15; INK4/ARF; tumor suppressor; polycomb; bladder cancer; PVT1

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MDPI and ACS Style

Hoffmann, M.J.; Dehn, J.; Droop, J.; Niegisch, G.; Niedworok, C.; Szarvas, T.; Schulz, W.A. Truncated Isoforms of lncRNA ANRIL Are Overexpressed in Bladder Cancer, But Do Not Contribute to Repression of INK4 Tumor Suppressors. Non-Coding RNA 2015, 1, 266-284. https://doi.org/10.3390/ncrna1030266

AMA Style

Hoffmann MJ, Dehn J, Droop J, Niegisch G, Niedworok C, Szarvas T, Schulz WA. Truncated Isoforms of lncRNA ANRIL Are Overexpressed in Bladder Cancer, But Do Not Contribute to Repression of INK4 Tumor Suppressors. Non-Coding RNA. 2015; 1(3):266-284. https://doi.org/10.3390/ncrna1030266

Chicago/Turabian Style

Hoffmann, Michèle J., Judith Dehn, Johanna Droop, Günter Niegisch, Christian Niedworok, Tibor Szarvas, and Wolfgang A. Schulz. 2015. "Truncated Isoforms of lncRNA ANRIL Are Overexpressed in Bladder Cancer, But Do Not Contribute to Repression of INK4 Tumor Suppressors" Non-Coding RNA 1, no. 3: 266-284. https://doi.org/10.3390/ncrna1030266

APA Style

Hoffmann, M. J., Dehn, J., Droop, J., Niegisch, G., Niedworok, C., Szarvas, T., & Schulz, W. A. (2015). Truncated Isoforms of lncRNA ANRIL Are Overexpressed in Bladder Cancer, But Do Not Contribute to Repression of INK4 Tumor Suppressors. Non-Coding RNA, 1(3), 266-284. https://doi.org/10.3390/ncrna1030266

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