Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.

A widespread downregulated expression of microRNAs (miRNAs) is commonly observed in human cancers. Similarly, deregulated expression of miRNA-processing pathway components, which results in the reduction of global miRNA expression, may also be associated with tumorigenesis. Here, we show that specif...

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Autores principales:	Takeshi Yoshikawa, Motoyuki Otsuka, Takahiro Kishikawa, Akemi Takata, Motoko Ohno, Chikako Shibata, Young Jun Kang, Haruhiko Yoshida, Kazuhiko Koike
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b60ac1bc3b44817ba49bb88dec6de94
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spelling	oai:doaj.org-article:0b60ac1bc3b44817ba49bb88dec6de942021-11-18T08:57:26ZUnique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.1932-620310.1371/journal.pone.0071969https://doaj.org/article/0b60ac1bc3b44817ba49bb88dec6de942013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24023722/?tool=EBIhttps://doaj.org/toc/1932-6203A widespread downregulated expression of microRNAs (miRNAs) is commonly observed in human cancers. Similarly, deregulated expression of miRNA-processing pathway components, which results in the reduction of global miRNA expression, may also be associated with tumorigenesis. Here, we show that specific ablation of Dicer1 in intestinal epithelial cells accelerates intestinal inflammation-associated tumorigenesis. This effect was apparent only when a single copy of Dicer1 was deleted, but not with complete Dicer1 ablation. DICER expression and subsequent mature miRNA levels were inversely correlated with the number of intact Dicer1 alleles. Because the expression levels of DICER were retained in tumors and its surrounding tissues even after induction of colitis-associated tumors, the effects of Dicer1 deletion were cell-autonomous. Although the expression levels of representative oncogenes and tumor suppressor genes were in most cases inversely correlated with the expression levels of DICER, some genes were not affected by Dicer1 deletion. Thus, deregulating the delicate balance between the expression levels of tumor-promoting and -suppressive genes may be crucial for tumorigenesis in this unique haploinsufficient case.Takeshi YoshikawaMotoyuki OtsukaTakahiro KishikawaAkemi TakataMotoko OhnoChikako ShibataYoung Jun KangHaruhiko YoshidaKazuhiko KoikePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e71969 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takeshi Yoshikawa Motoyuki Otsuka Takahiro Kishikawa Akemi Takata Motoko Ohno Chikako Shibata Young Jun Kang Haruhiko Yoshida Kazuhiko Koike Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.
description	A widespread downregulated expression of microRNAs (miRNAs) is commonly observed in human cancers. Similarly, deregulated expression of miRNA-processing pathway components, which results in the reduction of global miRNA expression, may also be associated with tumorigenesis. Here, we show that specific ablation of Dicer1 in intestinal epithelial cells accelerates intestinal inflammation-associated tumorigenesis. This effect was apparent only when a single copy of Dicer1 was deleted, but not with complete Dicer1 ablation. DICER expression and subsequent mature miRNA levels were inversely correlated with the number of intact Dicer1 alleles. Because the expression levels of DICER were retained in tumors and its surrounding tissues even after induction of colitis-associated tumors, the effects of Dicer1 deletion were cell-autonomous. Although the expression levels of representative oncogenes and tumor suppressor genes were in most cases inversely correlated with the expression levels of DICER, some genes were not affected by Dicer1 deletion. Thus, deregulating the delicate balance between the expression levels of tumor-promoting and -suppressive genes may be crucial for tumorigenesis in this unique haploinsufficient case.
format	article
author	Takeshi Yoshikawa Motoyuki Otsuka Takahiro Kishikawa Akemi Takata Motoko Ohno Chikako Shibata Young Jun Kang Haruhiko Yoshida Kazuhiko Koike
author_facet	Takeshi Yoshikawa Motoyuki Otsuka Takahiro Kishikawa Akemi Takata Motoko Ohno Chikako Shibata Young Jun Kang Haruhiko Yoshida Kazuhiko Koike
author_sort	Takeshi Yoshikawa
title	Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.
title_short	Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.
title_full	Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.
title_fullStr	Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.
title_full_unstemmed	Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.
title_sort	unique haploinsufficient role of the microrna-processing molecule dicer1 in a murine colitis-associated tumorigenesis model.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/0b60ac1bc3b44817ba49bb88dec6de94
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Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model.

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