A computational pipeline to identify new potential regulatory motifs in melanoma progression

Abstract

Molecular biology experiments allow to obtain reliable data about the expression of different classes of molecules involved in several cellular processes. This information is mostly static and does not give much clue about the causal relationships (i.e., regulation) among the different molecules. A typical scenario is the presence of a set of modulated mRNAs (up or down regulated) along with an over expression of one or more small non-coding RNAs molecules like miRNAs. To computationally identify the presence of transcriptional or post-transcriptional regulatory modules between one or more miRNAs and a set of target modulated genes, we propose a computational pipeline designed to integrate data from multiple online data repositories. The pipeline produces a set of three types of putative regulatory motifs involving coding genes, intronic miRNAs, and transcription factors. We used this pipeline to analyze the results of a set of expression experiments on a melanoma cell line that showed an over expression of miR-214 along with the modulation of a set of 73 other genes. The results suggest the presence of 27 putative regulatory modules involving miR-214, NFKB1, SREBPF2, miR- 33a and 9 out of the 73 miR-214 modulated genes (ALCAM, POSTN, TFAP2A, ADAM9, NCAM1, SEMA3A, PVRL2, JAG1, EGFR1). As a preliminary experimental validation we focused on 9 out of the 27 identified regulatory modules that involve miR-33a and SREBF2. The results confirm the importance of the predictions obtained with the presented computational approach.