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Carcinogenesis Advance Access published online on March 19, 2008
Carcinogenesis, doi:10.1093/carcin/bgn073
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Genetic variations of microRNAs in human cancer and their effects on the expression of miRNAs

Meiqun Wu1,§, Normand Jolicoeur2,§, Zhen Li1,§, Linhua Zhang1,2, Yves Fortin2, L'Abbe Denis 2, Zhenbao Yu2 and Shi-Hsiang Shen1,2,*

1. Department of Medicine, McGill University, Montréal, Québec, Canada, H3G 1A4
2 . Health Sector, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montréal, Québec, Canada, H4P 2R2
§ These authors equally contribute to this work

* Corresponding author: shi.shen{at}cnrc-nrc.gc.ca, Fax: 514-496-6319

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level to lead to mRNA degradation or repressed protein production. The expression of miRNA is deregulated in many types of cancers. To determine whether genetic alterations in miRNA genes are associated with cancers, we have systematically screened sequence variations in several hundred human miRNAs from over 100 human tumor tissues and 20 cancer cell lines. We identified 8 new single nucleotide polymorphisms (SNPs) and 14 novel mutations (or very rare SNPs) that specifically present in human cancers. These mutations/SNPs are distributed in the regions of pri-, pre- and even mature miRNAs, respectively. Importantly, while most of the mutations did not exert detectable effects on miRNA function, a G->A mutation at 19 nt downstream of miRNA let-7e led to a significant reduction of its expression in vivo, indicating that miRNA mutation could contribute to tumorigenesis. These data suggest that further screening for genetic variations in miRNA genes from a wide variety of human cancers should increase the discovery and identification of molecular diagnostic and therapeutic targets and complement the mutation analysis of consensus coding sequences in human cancers.

Key Words: MicroRNAs • Cancers • Mutations • SNPs • Expression • Secondary Structure

Received December 21, 2007; revised February 19, 2008; accepted March 7, 2008.


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