The apoptotic machinery as a biological complex system: analysis of its omics and evolution, identification of candidate genes for fourteen major types of cancer, and experimental validation in CML and neuroblastoma

• Main Authors: Li Destri Giovanni (Author), Santagati Maria (Author), Bertuccio Taschia (Author), Cafiso Viviana (Author), La Cava Piera (Author), Palumbo Giuseppe A (Author), Tandurella Igor (Author), Triberio Patrizio (Author), D'Agostino Vito (Author), Valenti Salvo (Author), Pernagallo Salvo (Author), Tomasello Luisa (Author), Salito Loredana (Author), Statello Luisa (Author), Scalia Marina (Author), Angelica Rosario (Author), Majorana Alessandra (Author), Guglielmino Maria R (Author), Duro Laura R (Author), Barbagallo Davide (Author), Ragusa Marco (Author), Di Pietro Cinzia (Author), Lanzafame Salvatore (Author), Di Raimondo Francesco (Author), Stefani Stefania (Author), Mishra Bud (Author), Purrello Michele (Author)
• Format: Book
• Published: BMC, 2009-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>Apoptosis is a critical biological phenomenon, executed under the guidance of the Apoptotic Machinery (AM), which allows the physiologic elimination of terminally differentiated, senescent or diseased cells. Because of its relevance to BioMedicine, we have sought to obtain a detailed characterization of AM Omics in <it>Homo sapiens</it>, namely its Genomics and Evolution, Transcriptomics, Proteomics, Interactomics, Oncogenomics, and Pharmacogenomics.</p> <p>Methods</p> <p>This project exploited the methodology commonly used in Computational Biology (i.e., mining of many <it>omics </it>databases of the web) as well as the High Throughput biomolecular analytical techniques.</p> <p>Results</p> <p>In <it>Homo sapiens </it>AM is comprised of 342 protein-encoding genes (possessing either anti- or pro-apoptotic activity, or a regulatory function) and 110 MIR-encoding genes targeting them: some have a critical role within the system (<it>core </it>AM nodes), others perform tissue-, pathway-, or disease-specific functions (<it>peripheral </it>AM nodes). By overlapping the cancer type-specific AM mutation map in the fourteen most frequent cancers in western societies (breast, colon, kidney, leukaemia, liver, lung, neuroblastoma, ovary, pancreas, prostate, skin, stomach, thyroid, and uterus) to their transcriptome, proteome and interactome in the same tumour type, we have identified the most prominent AM molecular alterations within each class. The comparison of the fourteen mutated AM networks (both protein- as MIR-based) has allowed us to pinpoint the hubs with a general and critical role in tumour development and, conversely, in cell physiology: in particular, we found that some of these had already been used as targets for pharmacological anticancer therapy. For a better understanding of the relationship between AM molecular alterations and pharmacological induction of apoptosis in cancer, we examined the expression of AM genes in K562 and SH-SY5Y after anticancer treatment.</p> <p>Conclusion</p> <p>We believe that our data on the Apoptotic Machinery will lead to the identification of new cancer genes and to the discovery of new biomarkers, which could then be used to profile cancers for diagnostic purposes and to pinpoint new targets for pharmacological therapy. This approach could pave the way for future studies and applications in molecular and clinical Medicine with important perspectives both for Oncology as for Regenerative Medicine.</p>

Item Description

10.1186/1755-8794-2-20
1755-8794