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

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TypeArticle
Subjectanalysis; Cell Line; Gene Expression; Genes; Human; Mutation; pha; Protein; protein production; Rna
AbstractMicroRNAs (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
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; National Research Council Canada; NRC Institute for Biological Sciences
Peer reviewedNo
NRC number2249551
NPARC number3540307
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Record identifier9aed8b3d-c0b3-47be-8daa-0ecf2b67f463
Record created2009-03-01
Record modified2016-05-09
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