Cargando…

High Positive Correlations between ANRIL and p16-CDKN2A/p15-CDKN2B/p14-ARF Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an ANRIL–ARF Bidirectional Promoter

The CDKN2B-AS1 gene, also called ANRIL, is located at the human CDKN2A/B locus at 9p21.3 and transcribed by RNA polymerase II into a long non-coding RNA of 3834 bp. The CDKN2B-AS1 gene overlaps a critical region of 125 kb covering the CDKN2B gene. The CDKN2A/B locus encompasses three major tumor sup...

Descripción completa

Detalles Bibliográficos
Autores principales: Drak Alsibai, Kinan, Vacher, Sophie, Meseure, Didier, Nicolas, Andre, Lae, Marick, Schnitzler, Anne, Chemlali, Walid, Cros, Jerome, Longchampt, Elisabeth, Cacheux, Wulfran, Pignot, Geraldine, Callens, Celine, Pasmant, Eric, Allory, Yves, Bieche, Ivan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789474/
https://www.ncbi.nlm.nih.gov/pubmed/31438464
http://dx.doi.org/10.3390/ncrna5030044
_version_ 1783458625480556544
author Drak Alsibai, Kinan
Vacher, Sophie
Meseure, Didier
Nicolas, Andre
Lae, Marick
Schnitzler, Anne
Chemlali, Walid
Cros, Jerome
Longchampt, Elisabeth
Cacheux, Wulfran
Pignot, Geraldine
Callens, Celine
Pasmant, Eric
Allory, Yves
Bieche, Ivan
author_facet Drak Alsibai, Kinan
Vacher, Sophie
Meseure, Didier
Nicolas, Andre
Lae, Marick
Schnitzler, Anne
Chemlali, Walid
Cros, Jerome
Longchampt, Elisabeth
Cacheux, Wulfran
Pignot, Geraldine
Callens, Celine
Pasmant, Eric
Allory, Yves
Bieche, Ivan
author_sort Drak Alsibai, Kinan
collection PubMed
description The CDKN2B-AS1 gene, also called ANRIL, is located at the human CDKN2A/B locus at 9p21.3 and transcribed by RNA polymerase II into a long non-coding RNA of 3834 bp. The CDKN2B-AS1 gene overlaps a critical region of 125 kb covering the CDKN2B gene. The CDKN2A/B locus encompasses three major tumor suppressors juxtaposed and joined into a p16-CDKN2A/p15-CDKN2B/p14-ARF gene cluster. CDKN2A encodes splice variants p16-CDKN2A and p14-ARF, and CDKN2B encodes p15-CDKN2B. ANRIL shares a bidirectional promoter with the p14-ARF gene and is transcribed from the opposite strand to the cluster. We performed an analysis of the expression level of ANRIL and tumor suppressor p16-CDKN2A, p15-CDKN2B, and p14-ARF genes using quantitative RT-PCR in a multitumor panel. We observed the overexpression of the four genes ANRIL, p16-CDKN2A, p15-CDKN2B, and p14-ARF in the great majority of the 17 different cancer types. ANRIL was upregulated in 13/17 tumors compared to normal tissues, ranging from 5% (prostate cancer) to 91% (cervix cancer), with variable expression of p16-CDKN2A, p15-CDKN2B, and p14-ARF genes. A high positive correlation was identified between levels of expression of ANRIL and the three tumor suppressors. The strongest positive association was observed with p14-ARF (p < 0.001) in all but one (lung squamous cell carcinoma) of the examined tumor types. This correlation suggests coordinated deregulated mechanisms in all cancer types through aberrant activation of a bidirectional p14-ARF/ANRIL promoter. Furthermore, significant positive correlation was unexpectedly established in prostatic carcinomas, in contradiction with previous data.
format Online
Article
Text
id pubmed-6789474
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-67894742019-10-16 High Positive Correlations between ANRIL and p16-CDKN2A/p15-CDKN2B/p14-ARF Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an ANRIL–ARF Bidirectional Promoter Drak Alsibai, Kinan Vacher, Sophie Meseure, Didier Nicolas, Andre Lae, Marick Schnitzler, Anne Chemlali, Walid Cros, Jerome Longchampt, Elisabeth Cacheux, Wulfran Pignot, Geraldine Callens, Celine Pasmant, Eric Allory, Yves Bieche, Ivan Noncoding RNA Article The CDKN2B-AS1 gene, also called ANRIL, is located at the human CDKN2A/B locus at 9p21.3 and transcribed by RNA polymerase II into a long non-coding RNA of 3834 bp. The CDKN2B-AS1 gene overlaps a critical region of 125 kb covering the CDKN2B gene. The CDKN2A/B locus encompasses three major tumor suppressors juxtaposed and joined into a p16-CDKN2A/p15-CDKN2B/p14-ARF gene cluster. CDKN2A encodes splice variants p16-CDKN2A and p14-ARF, and CDKN2B encodes p15-CDKN2B. ANRIL shares a bidirectional promoter with the p14-ARF gene and is transcribed from the opposite strand to the cluster. We performed an analysis of the expression level of ANRIL and tumor suppressor p16-CDKN2A, p15-CDKN2B, and p14-ARF genes using quantitative RT-PCR in a multitumor panel. We observed the overexpression of the four genes ANRIL, p16-CDKN2A, p15-CDKN2B, and p14-ARF in the great majority of the 17 different cancer types. ANRIL was upregulated in 13/17 tumors compared to normal tissues, ranging from 5% (prostate cancer) to 91% (cervix cancer), with variable expression of p16-CDKN2A, p15-CDKN2B, and p14-ARF genes. A high positive correlation was identified between levels of expression of ANRIL and the three tumor suppressors. The strongest positive association was observed with p14-ARF (p < 0.001) in all but one (lung squamous cell carcinoma) of the examined tumor types. This correlation suggests coordinated deregulated mechanisms in all cancer types through aberrant activation of a bidirectional p14-ARF/ANRIL promoter. Furthermore, significant positive correlation was unexpectedly established in prostatic carcinomas, in contradiction with previous data. MDPI 2019-08-21 /pmc/articles/PMC6789474/ /pubmed/31438464 http://dx.doi.org/10.3390/ncrna5030044 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Drak Alsibai, Kinan
Vacher, Sophie
Meseure, Didier
Nicolas, Andre
Lae, Marick
Schnitzler, Anne
Chemlali, Walid
Cros, Jerome
Longchampt, Elisabeth
Cacheux, Wulfran
Pignot, Geraldine
Callens, Celine
Pasmant, Eric
Allory, Yves
Bieche, Ivan
High Positive Correlations between ANRIL and p16-CDKN2A/p15-CDKN2B/p14-ARF Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an ANRIL–ARF Bidirectional Promoter
title High Positive Correlations between ANRIL and p16-CDKN2A/p15-CDKN2B/p14-ARF Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an ANRIL–ARF Bidirectional Promoter
title_full High Positive Correlations between ANRIL and p16-CDKN2A/p15-CDKN2B/p14-ARF Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an ANRIL–ARF Bidirectional Promoter
title_fullStr High Positive Correlations between ANRIL and p16-CDKN2A/p15-CDKN2B/p14-ARF Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an ANRIL–ARF Bidirectional Promoter
title_full_unstemmed High Positive Correlations between ANRIL and p16-CDKN2A/p15-CDKN2B/p14-ARF Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an ANRIL–ARF Bidirectional Promoter
title_short High Positive Correlations between ANRIL and p16-CDKN2A/p15-CDKN2B/p14-ARF Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an ANRIL–ARF Bidirectional Promoter
title_sort high positive correlations between anril and p16-cdkn2a/p15-cdkn2b/p14-arf gene cluster overexpression in multi-tumor types suggest deregulated activation of an anril–arf bidirectional promoter
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789474/
https://www.ncbi.nlm.nih.gov/pubmed/31438464
http://dx.doi.org/10.3390/ncrna5030044
work_keys_str_mv AT drakalsibaikinan highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT vachersophie highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT meseuredidier highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT nicolasandre highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT laemarick highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT schnitzleranne highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT chemlaliwalid highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT crosjerome highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT longchamptelisabeth highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT cacheuxwulfran highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT pignotgeraldine highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT callensceline highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT pasmanteric highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT alloryyves highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter
AT biecheivan highpositivecorrelationsbetweenanrilandp16cdkn2ap15cdkn2bp14arfgeneclusteroverexpressioninmultitumortypessuggestderegulatedactivationofananrilarfbidirectionalpromoter