Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers
George A. Calin,Cinzia Sevignani,Calin Dan Dumitru,Terry Hyslop,Evan Noch,Sai Yendamuri,Masayoshi Shimizu,Sashi Rattan,Florencia Bullrich,Massimo Negrini,Massimo Negrini,Carlo M. Croce +11 more
TLDR
These data provide a catalog of miR genes that may have roles in cancer and argue that the full complement of miRs in a genome may be extensively involved in cancers.Abstract:
A large number of tiny noncoding RNAs have been cloned and named microRNAs (miRs). Recently, we have reported that miR-15a and miR-16a, located at 13q14, are frequently deleted and/or down-regulated in patients with B cell chronic lymphocytic leukemia, a disorder characterized by increased survival. To further investigate the possible involvement of miRs in human cancers on a genome-wide basis, we have mapped 186 miRs and compared their location to the location of previous reported nonrandom genetic alterations. Here, we show that miR genes are frequently located at fragile sites, as well as in minimal regions of loss of heterozygosity, minimal regions of amplification (minimal amplicons), or common breakpoint regions. Overall, 98 of 186 (52.5%) of miR genes are in cancer-associated genomic regions or in fragile sites. Moreover, by Northern blotting, we have shown that several miRs located in deleted regions have low levels of expression in cancer samples. These data provide a catalog of miR genes that may have roles in cancer and argue that the full complement of miRs in a genome may be extensively involved in cancers.read more
Citations
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MicroRNA signatures in human cancers
George A. Calin,Carlo M. Croce +1 more
TL;DR: MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment and has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
Journal Article
MicroRNA signatures in human cancers
George A. Calin,Carlo M. Croce +1 more
TL;DR: The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery as discussed by the authors.
Journal ArticleDOI
MicroRNAs: small RNAs with a big role in gene regulation
Lin He,Gregory J. Hannon +1 more
TL;DR: Two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events and indicate the existence of multiple RISCs that carry out related but specific biological functions.
Journal Article
Oncomirs : microRNAs with a role in cancer
TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
Journal ArticleDOI
Oncomirs — microRNAs with a role in cancer
TL;DR: Evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes.
References
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Journal ArticleDOI
Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia
George A. Calin,Calin Dan Dumitru,Masayoshi Shimizu,Roberta Bichi,Simona Zupo,Evan Noch,Hansjuerg Aldler,Sashi Rattan,Michael J. Keating,Kanti R. Rai,Laura Z. Rassenti,Thomas J. Kipps,Massimo Negrini,Florencia Bullrich,Carlo M. Croce +14 more
TL;DR: Detailed deletion and expression analysis shows that miR15 and miR16 are located within a 30-kb region of loss in CLL, and that both genes are deleted or down-regulated in the majority (≈68%) of CLL cases.
Journal ArticleDOI
Identification of novel genes coding for small expressed RNAs.
TL;DR: It is shown that many 21- and 22-nt expressed RNAs, termed microRNAs, exist in invertebrates and vertebrates and that some of these novel RNAs are highly conserved, which suggests that sequence-specific, posttranscriptional regulatory mechanisms mediated by smallRNAs are more general than previously appreciated.
Journal ArticleDOI
An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans
TL;DR: Two small temporal RNAs, lin-4 andlet-7, control developmental timing in Caenorhabditis elegans and are found to be members of a large class of 21- to 24-nucleotide noncodingRNAs, called microRNAs (miRNAs), which imply that, as a class, miRNAs have broad regulatory functions in animals.
Journal ArticleDOI
Systematic functional analysis of the Caenorhabditis elegans genome using RNAi
Ravi S. Kamath,Andrew G. Fraser,Andrew G. Fraser,Yan Dong,Gino B. Poulin,Richard Durbin,Monica Gotta,Alexander Kanapin,Nathalie Le Bot,Sergio Moreno,Sergio Moreno,Marc Sohrmann,David P. Welchman,Peder Zipperlen,Julie Ahringer +14 more
TL;DR: It is found that genes of similar functions are clustered in distinct, multi-megabase regions of individual chromosomes; genes in these regions tend to share transcriptional profiles.
Journal ArticleDOI
Identification of tissue-specific microRNAs from mouse
Mariana Lagos-Quintana,Reinhard Rauhut,Abdullah Yalcin,Jutta Meyer,Winfried Lendeckel,Thomas Tuschl +5 more
TL;DR: 34 novel miRNAs were identified by tissue-specific cloning of approximately 21-nucleotide RNAs from mouse and a miRNA was identified that appears to be the fruitfly and mammalian ortholog of C. elegans lin-4 stRNA.
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