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.