Expressional alterations in functional ultra-conserved non-coding RNAs in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells

Hdl Handle:
http://hdl.handle.net/10147/283216
Title:
Expressional alterations in functional ultra-conserved non-coding RNAs in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells
Authors:
Watters, Karen M; Bryan, Kenneth; Foley, Niamh H; Meehan, Maria; Stallings, Raymond L
Citation:
BMC Cancer. 2013 Apr 08;13(1):184
Issue Date:
8-Apr-2013
URI:
http://dx.doi.org/10.1186/1471-2407-13-184; http://hdl.handle.net/10147/283216
Abstract:
Abstract 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.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorWatters, Karen M-
dc.contributor.authorBryan, Kenneth-
dc.contributor.authorFoley, Niamh H-
dc.contributor.authorMeehan, Maria-
dc.contributor.authorStallings, Raymond L-
dc.date.accessioned2013-04-19T13:17:55Z-
dc.date.available2013-04-19T13:17:55Z-
dc.date.issued2013-04-08-
dc.identifier.citationBMC Cancer. 2013 Apr 08;13(1):184-
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2407-13-184-
dc.identifier.urihttp://hdl.handle.net/10147/283216-
dc.description.abstractAbstract 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.-
dc.titleExpressional alterations in functional ultra-conserved non-coding RNAs in response to all-trans retinoic acid - induced differentiation in neuroblastoma cells-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderKaren M Watters et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2013-04-15T15:07:06Z-
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