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Expressional alterations in functional ultra-conserved non-coding rnas in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells
BACKGROUND: Ultra-conserved regions (UCRs) are segments of the genome (≥ 200 bp) that exhibit 100% DNA sequence conservation between human, mouse and rat. Transcribed UCRs (T-UCRs) have been shown to be differentially expressed in cancers versus normal tissue, indicating a possible role in carcinoge...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626850/ https://www.ncbi.nlm.nih.gov/pubmed/23565812 http://dx.doi.org/10.1186/1471-2407-13-184 |
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author | Watters, Karen M Bryan, Kenneth Foley, Niamh H Meehan, Maria Stallings, Raymond L |
author_facet | Watters, Karen M Bryan, Kenneth Foley, Niamh H Meehan, Maria Stallings, Raymond L |
author_sort | Watters, Karen M |
collection | PubMed |
description | BACKGROUND: Ultra-conserved regions (UCRs) are segments of the genome (≥ 200 bp) that exhibit 100% DNA sequence conservation between human, mouse and rat. Transcribed UCRs (T-UCRs) have been shown to be differentially expressed in cancers versus normal tissue, indicating a possible role in carcinogenesis. All-trans-retinoic acid (ATRA) causes some neuroblastoma (NB) cell lines to undergo differentiation and leads to a significant decrease in the oncogenic transcription factor MYCN. Here, we examine the impact of ATRA treatment on T-UCR expression and investigate the biological significance of these changes. METHODS: We designed a custom tiling microarray to profile the expression of 481 T-UCRs in sense and anti-sense orientation (962 potential transcripts) in untreated and ATRA-treated neuroblastoma cell lines (SH-SY5Y, SK-N-BE, LAN-5). Following identification of significantly differentially expressed T-UCRs, we carried out siRNA knockdown and gene expression microarray analysis to investigate putative functional roles for selected T-UCRs. RESULTS: Following ATRA-induced differentiation, 32 T-UCRs were differentially expressed (16 up-regulated, 16 down-regulated) across all three cell lines. Further insight into the possible role of T-UC.300A, an independent transcript whose expression is down-regulated following ATRA was achieved by siRNA knockdown, resulting in the decreased viability and invasiveness of ATRA-responsive cell lines. Gene expression microarray analysis following knockdown of T-UC.300A revealed a number of genes whose expression was altered by changing T-UC.300A levels and that might play a role in the increased proliferation and invasion of NB cells prior to ATRA-treatment. CONCLUSIONS: Our results indicate that significant numbers of T-UCRs have altered expression levels in response to ATRA. While the precise roles that T-UCRs might play in cancer or in normal development are largely unknown and an important area for future study, our findings strongly indicate that the function of non-coding RNA T-UC.300A is connected with proliferation, invasion and the inhibition of differentiation of neuroblastoma cell lines prior to ATRA treatment. |
format | Online Article Text |
id | pubmed-3626850 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36268502013-04-16 Expressional alterations in functional ultra-conserved non-coding rnas in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells Watters, Karen M Bryan, Kenneth Foley, Niamh H Meehan, Maria Stallings, Raymond L BMC Cancer Research Article BACKGROUND: Ultra-conserved regions (UCRs) are segments of the genome (≥ 200 bp) that exhibit 100% DNA sequence conservation between human, mouse and rat. Transcribed UCRs (T-UCRs) have been shown to be differentially expressed in cancers versus normal tissue, indicating a possible role in carcinogenesis. All-trans-retinoic acid (ATRA) causes some neuroblastoma (NB) cell lines to undergo differentiation and leads to a significant decrease in the oncogenic transcription factor MYCN. Here, we examine the impact of ATRA treatment on T-UCR expression and investigate the biological significance of these changes. METHODS: We designed a custom tiling microarray to profile the expression of 481 T-UCRs in sense and anti-sense orientation (962 potential transcripts) in untreated and ATRA-treated neuroblastoma cell lines (SH-SY5Y, SK-N-BE, LAN-5). Following identification of significantly differentially expressed T-UCRs, we carried out siRNA knockdown and gene expression microarray analysis to investigate putative functional roles for selected T-UCRs. RESULTS: Following ATRA-induced differentiation, 32 T-UCRs were differentially expressed (16 up-regulated, 16 down-regulated) across all three cell lines. Further insight into the possible role of T-UC.300A, an independent transcript whose expression is down-regulated following ATRA was achieved by siRNA knockdown, resulting in the decreased viability and invasiveness of ATRA-responsive cell lines. Gene expression microarray analysis following knockdown of T-UC.300A revealed a number of genes whose expression was altered by changing T-UC.300A levels and that might play a role in the increased proliferation and invasion of NB cells prior to ATRA-treatment. CONCLUSIONS: Our results indicate that significant numbers of T-UCRs have altered expression levels in response to ATRA. While the precise roles that T-UCRs might play in cancer or in normal development are largely unknown and an important area for future study, our findings strongly indicate that the function of non-coding RNA T-UC.300A is connected with proliferation, invasion and the inhibition of differentiation of neuroblastoma cell lines prior to ATRA treatment. BioMed Central 2013-04-08 /pmc/articles/PMC3626850/ /pubmed/23565812 http://dx.doi.org/10.1186/1471-2407-13-184 Text en Copyright © 2013 Watters et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Watters, Karen M Bryan, Kenneth Foley, Niamh H Meehan, Maria Stallings, Raymond L Expressional alterations in functional ultra-conserved non-coding rnas in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells |
title | Expressional alterations in functional ultra-conserved non-coding rnas in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells |
title_full | Expressional alterations in functional ultra-conserved non-coding rnas in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells |
title_fullStr | Expressional alterations in functional ultra-conserved non-coding rnas in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells |
title_full_unstemmed | Expressional alterations in functional ultra-conserved non-coding rnas in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells |
title_short | Expressional alterations in functional ultra-conserved non-coding rnas in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells |
title_sort | expressional alterations in functional ultra-conserved non-coding rnas in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626850/ https://www.ncbi.nlm.nih.gov/pubmed/23565812 http://dx.doi.org/10.1186/1471-2407-13-184 |
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