Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.

Alternative polyadenylation (APA) could result in mRNA isoforms with variable lengths of 3' UTRs. Gain of microRNA target sites in the 3' UTR of a long mRNA isoform may cause different regulation from the corresponding short isoform. It has been known that cancer cells globally exhibit a l...

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Autores principales:	Hao-Han Liaw, Chen-Ching Lin, Hsueh-Fen Juan, Hsuan-Cheng Huang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd686a9fb3634d03a915bdac209401c7
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spelling	oai:doaj.org-article:cd686a9fb3634d03a915bdac209401c72021-11-18T07:56:33ZDifferential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.1932-620310.1371/journal.pone.0056958https://doaj.org/article/cd686a9fb3634d03a915bdac209401c72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23437281/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Alternative polyadenylation (APA) could result in mRNA isoforms with variable lengths of 3' UTRs. Gain of microRNA target sites in the 3' UTR of a long mRNA isoform may cause different regulation from the corresponding short isoform. It has been known that cancer cells globally exhibit a lower ratio of long and short isoforms (LSR); that is, they tend to express larger amounts of short isoforms. The objective of this study is to illustrate the relationship between microRNA differential regulation and LSR. We retrieved public APA annotations and isoform expression profiles of breast cancer and normal cells from a high-throughput sequencing method study specific for the mRNA 3' end. Combining microRNA expression profiles, we performed statistical analysis to reveal and estimate microRNA regulation on APA patterns in a global scale. First, we found that the amount of microRNA target sites in the alternative UTR (aUTR), the region only present in long isoforms, could affect the LSR of the target genes. Second, we observed that the genes whose aUTRs were targeted by up-regulated microRNAs in cancer cells had an overall lower LSR. Furthermore, the target sites of up-regulated microRNAs tended to appear in aUTRs. Finally, we demonstrated that the amount of target sites for up-regulated microRNAs in aUTRs correlated with the LSR change between cancer and normal cells. The results indicate that up-regulation of microRNAs might cause lower LSRs of target genes in cancer cells through degradation of their long isoforms. Our findings provide evidence of how microRNAs might play a crucial role in APA pattern shifts from normal to cancerous or proliferative states.Hao-Han LiawChen-Ching LinHsueh-Fen JuanHsuan-Cheng HuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56958 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hao-Han Liaw Chen-Ching Lin Hsueh-Fen Juan Hsuan-Cheng Huang Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.
description	Alternative polyadenylation (APA) could result in mRNA isoforms with variable lengths of 3' UTRs. Gain of microRNA target sites in the 3' UTR of a long mRNA isoform may cause different regulation from the corresponding short isoform. It has been known that cancer cells globally exhibit a lower ratio of long and short isoforms (LSR); that is, they tend to express larger amounts of short isoforms. The objective of this study is to illustrate the relationship between microRNA differential regulation and LSR. We retrieved public APA annotations and isoform expression profiles of breast cancer and normal cells from a high-throughput sequencing method study specific for the mRNA 3' end. Combining microRNA expression profiles, we performed statistical analysis to reveal and estimate microRNA regulation on APA patterns in a global scale. First, we found that the amount of microRNA target sites in the alternative UTR (aUTR), the region only present in long isoforms, could affect the LSR of the target genes. Second, we observed that the genes whose aUTRs were targeted by up-regulated microRNAs in cancer cells had an overall lower LSR. Furthermore, the target sites of up-regulated microRNAs tended to appear in aUTRs. Finally, we demonstrated that the amount of target sites for up-regulated microRNAs in aUTRs correlated with the LSR change between cancer and normal cells. The results indicate that up-regulation of microRNAs might cause lower LSRs of target genes in cancer cells through degradation of their long isoforms. Our findings provide evidence of how microRNAs might play a crucial role in APA pattern shifts from normal to cancerous or proliferative states.
format	article
author	Hao-Han Liaw Chen-Ching Lin Hsueh-Fen Juan Hsuan-Cheng Huang
author_facet	Hao-Han Liaw Chen-Ching Lin Hsueh-Fen Juan Hsuan-Cheng Huang
author_sort	Hao-Han Liaw
title	Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.
title_short	Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.
title_full	Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.
title_fullStr	Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.
title_full_unstemmed	Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.
title_sort	differential microrna regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/cd686a9fb3634d03a915bdac209401c7
work_keys_str_mv	AT haohanliaw differentialmicrornaregulationcorrelateswithalternativepolyadenylationpatternbetweenbreastcancerandnormalcells AT chenchinglin differentialmicrornaregulationcorrelateswithalternativepolyadenylationpatternbetweenbreastcancerandnormalcells AT hsuehfenjuan differentialmicrornaregulationcorrelateswithalternativepolyadenylationpatternbetweenbreastcancerandnormalcells AT hsuanchenghuang differentialmicrornaregulationcorrelateswithalternativepolyadenylationpatternbetweenbreastcancerandnormalcells
_version_	1718422757434195968

Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.

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