Author:
Di Pietro Cinzia,Ragusa Marco,Barbagallo Davide,Duro Laura R,Guglielmino Maria R,Majorana Alessandra,Angelica Rosario,Scalia Marina,Statello Luisa,Salito Loredana,Tomasello Luisa,Pernagallo Salvo,Valenti Salvo,D'Agostino Vito,Triberio Patrizio,Tandurella Igor,Palumbo Giuseppe A,La Cava Piera,Cafiso Viviana,Bertuccio Taschia,Santagati Maria,Li Destri Giovanni,Lanzafame Salvatore,Di Raimondo Francesco,Stefani Stefania,Mishra Bud,Purrello Michele
Abstract
Abstract
Background
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 Homo sapiens, namely its Genomics and Evolution, Transcriptomics, Proteomics, Interactomics, Oncogenomics, and Pharmacogenomics.
Methods
This project exploited the methodology commonly used in Computational Biology (i.e., mining of many omics databases of the web) as well as the High Throughput biomolecular analytical techniques.
Results
In Homo sapiens 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 (core AM nodes), others perform tissue-, pathway-, or disease-specific functions (peripheral 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.
Conclusion
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.
Publisher
Springer Science and Business Media LLC
Subject
Genetics(clinical),Genetics
Cited by
21 articles.
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