Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers

TLDR

MicroRNAs (miRs) are a large class of tiny noncoding RNAs that have been cloned and named. The study aimed to investigate the genome‑wide involvement of miRs in human cancers by mapping 186 miRs and comparing their genomic locations to previously reported nonrandom genetic alterations. The authors mapped the 186 miRs across the human genome and compared their positions to known fragile sites, regions of loss of heterozygosity, minimal amplicons, and common breakpoint regions. They found that 52.5 % of miR genes reside in cancer‑associated genomic regions or fragile sites, many of which are deleted or down‑regulated in cancer samples, providing a catalog of miRs that may play roles in tumorigenesis.

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.