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Overgrowth caused by misexpression of a microRNA with dispensable wild-type function


Nairz, K; Rottig, C; Rintelen, F; Zdobnov, E; Moser, M; Hafen, E (2006). Overgrowth caused by misexpression of a microRNA with dispensable wild-type function. Developmental Biology, 291(2):314-324.

Abstract

MicroRNAs (miRNAs) represent an abundant class of non-coding RNAs that negatively regulate gene expression, primarily at the post-transcriptional level. miRNA genes are frequently located in proximity to fragile chromosomal sites associated with cancers and amplification of a miRNA cluster has been correlated with the etiology of lymphomas and solid tumors. The oncogenic potential of a miRNA polycistron has recently been demonstrated in vivo. Here, we show that misexpression of the Drosophila miRNA mirvana/mir-278 in the developing eye causes massive overgrowth, in part due to inhibition of apoptosis. A single base substitution affecting the mature miRNA blocks the gain-of-function phenotype but is not associated with a detectable reduction-of-function phenotype when homozygous. This result demonstrates that misexpressed miRNAs may acquire novel functions that cause unscheduled proliferation in vivo and thus exemplifies the potential of miRNAs to promote tumor formation.

MicroRNAs (miRNAs) represent an abundant class of non-coding RNAs that negatively regulate gene expression, primarily at the post-transcriptional level. miRNA genes are frequently located in proximity to fragile chromosomal sites associated with cancers and amplification of a miRNA cluster has been correlated with the etiology of lymphomas and solid tumors. The oncogenic potential of a miRNA polycistron has recently been demonstrated in vivo. Here, we show that misexpression of the Drosophila miRNA mirvana/mir-278 in the developing eye causes massive overgrowth, in part due to inhibition of apoptosis. A single base substitution affecting the mature miRNA blocks the gain-of-function phenotype but is not associated with a detectable reduction-of-function phenotype when homozygous. This result demonstrates that misexpressed miRNAs may acquire novel functions that cause unscheduled proliferation in vivo and thus exemplifies the potential of miRNAs to promote tumor formation.

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29 citations in Web of Science®
28 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Zoology (former)
Dewey Decimal Classification:570 Life sciences; biology
590 Animals (Zoology)
Language:English
Date:15 March 2006
Deposited On:11 Feb 2008 12:17
Last Modified:05 Apr 2016 12:15
Publisher:Elsevier
ISSN:0012-1606
Publisher DOI:10.1016/j.ydbio.2005.11.047
PubMed ID:16443211

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