A New miRNA Motif Protects Pathways' Expression in Gene Regulatory Networks

The continuing discovery of new functions and classes of small non-coding RNAs is suggesting the presence of regulatory mechanisms far more complex than the ones identified so far. In our computational analysis of a large set of public available databases, we found statistical evidence of an inter-pathway regulatory motif, not previously described, that reveals a new protective role miRNAs may play in the successful activation of a pathway. This paper reports the main outcomes of this analysis

A New miRNA Motif Protects Pathways’ Expression in Gene Regulatory Networks

The continuing discovery of new functions and classes of small non-coding RNAs is suggesting the presence of regulatory mechanisms far more complex than the ones identified so far. In our computational analysis of a large set of public available databases, we found statistical evidence of an inter-pathway regulatory motif, not previously described, that reveals a new protective role miRNAs may play in the successful activation of a pathway. This paper reports the main outcomes of this analysis

A Computational Study to Identify TP53 and SREBF2 as Regulation Mediators of miR-214 in Melanoma Progression

In the complex world of post-transcriptional regulation, miR-214 is known to control in vitro tumor cell move- ment and survival to anoikis, as well as in vivo malignant cell extravasation from blood vessels and lung metastasis formation. miR-214 has also been found to be highly expressed in human melanomas, and to directly and indirectly regulate several genes involved in tumor progression and in the establishment of dis- tant metastases (Penna et al., 2011). In this work, we exploit a computational pipeline integrating data from multiple online data repositories to identify the presence of transcriptional or post-transcriptional regulatory modules involving miR-214 and a set of 73 previously identified miR-214 regulated genes. We identified 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 pre- liminary experimental validation we focused on 9 out of the 27 identified regulatory modules that involve two main players, miR-33a and SREBF2. The results confirm the importance of the predictions obtained with the presented computational approach

A systematic analysis of a mi-RNA inter-pathway regulatory motif

Background The continuing discovery of new types and functions of small non-coding RNAs is suggesting the presence of regulatory mechanisms far more complex than the ones currently used to study and design Gene Regulatory Networks. Just focusing on the roles of micro RNAs (miRNAs), they have been found to be part of several intra-pathway regulatory motifs. However, inter-pathway regulatory mechanisms have been often neglected and require further investigation. Results In this paper we present the result of a systems biology study aimed at analyzing a high-level inter-pathway regulatory motif called Pathway Protection Loop, not previously described, in which miRNAs seem to play a crucial role in the successful behavior and activation of a pathway. Through the automatic analysis of a large set of public available databases, we found statistical evidence that this inter-pathway regulatory motif is very common in several classes of KEGG Homo Sapiens pathways and concurs in creating a complex regulatory network involving several pathways connected by this specific motif. The role of this motif seems also confirmed by a deeper review of other research activities on selected representative pathways. Conclusions Although previous studies suggested transcriptional regulation mechanism at the pathway level such as the Pathway Protection Loop, a high-level analysis like the one proposed in this paper is still missing. The understanding of higher-level regulatory motifs could, as instance, lead to new approaches in the identification of therapeutic targets because it could unveil new and "indirect" paths to activate or silence a target pathway. However, a lot of work still needs to be done to better uncover this high-level inter-pathway regulation including enlarging the analysis to other small non-coding RNA molecules