Abstract
MotivationmiRNAs are potent regulators of gene expression and modulate multiple cellular processes in physiology and pathology. Deregulation of miRNAs expression has been found in various cancer types, thus, miRNAs may be potential targets for cancer therapy. However, the mechanisms through which miRNAs are regulated in cancer remain unclear. Therefore, the identification of transcriptional factor–miRNA crosstalk is one of the most update aspects of the study of miRNAs regulation.ResultsIn the present study we describe the development of a fast and user-friendly software, named infinity, able to find the presence of DNA matrices, such as binding sequences for transcriptional factors, on ~65kb (kilobase) of 939 human miRNA genomic sequences, simultaneously. Of note, the power of this software has been validated in vivo by performing chromatin immunoprecipitation assays on a subset of new in silico identified target sequences (CCAAT) for the transcription factor NF-Y on colon cancer deregulated miRNA loci. Moreover, for the first time, we have demonstrated that NF-Y, through its CCAAT binding activity, regulates the expression of miRNA-181a, -181b, -21, -17, -130b, -301b in colon cancer cells.ConclusionsThe infinity software that we have developed is a powerful tool to underscore new TF/miRNA regulatory networks.Availability and ImplementationInfinity was implemented in pure Java using Eclipse framework, and runs on Linux and MS Windows machine, with MySQL database. The software is freely available on the web at https://github.com/bio-devel/infinity. The website is implemented in JavaScript, PHP and HTML with all major browsers supported.
Highlights
MicroRNAs are a recently discovered group of small RNA molecules of about 20– 25 nucleotides in length involved in the regulation of gene expression [1]
In the present study we describe the development of a fast and user-friendly software, named infinity, able to find the presence of DNA matrices, such as binding sequences for transcriptional factors, on ~65kb of 939 human miRNA genomic sequences, simultaneously
The power of this software has been validated in vivo by performing chromatin immunoprecipitation assays on a subset of new in silico identified target sequences (CCAAT) for the transcription factor NF-Y on colon cancer deregulated miRNA loci
Summary
MicroRNAs (miRNAs) are a recently discovered group of small RNA molecules of about 20– 25 nucleotides in length involved in the regulation of gene expression [1] They exert their function by binding to the 3'-untranslated region of a subset of mRNAs, this results in repression of translation or directing the sequence-specific degradation of their target mRNAs. Computational predictions, supported by experimental evidences, indicate that miRNAs regulate a large fraction of metazoan genes [2,3,4,5]. Analysis of transcriptome profiles during cellular transformation identified the CCAAT box as over-represented in promoters of genes overexpressed in diverse types of cancers, breast, colon, thyroid, prostate and leukemia This strongly indicates the involvement of NF-Y in cancer-associated pathways [18]. As a proof of principle of our software, we challenged infinity to find NF-Y consensus sequences, CCAAT boxes, on the promoters of human miRNAs and its predictive power has been confirmed by in vivo chromatin immunoprecipitation (ChIPs) and loss of function experiments
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call