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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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 |
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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 |
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