Environmental and Lifestyle Cancer Risk Factors: Shaping Extracellular Vesicle OncomiRs and Paving the Path to Cancer Development

Author:

Bollati Valentina12ORCID,Monti Paola1ORCID,Biganzoli Davide3ORCID,Marano Giuseppe4,Favero Chiara1,Iodice Simona1ORCID,Ferrari Luca12ORCID,Dioni Laura1,Bianchi Francesca56,Pesatori Angela Cecilia12ORCID,Biganzoli Elia Mario4ORCID

Affiliation:

1. Epiget Lab, Department of Clinical Sciences and Community Health, University of Milan, 20133 Milan, Italy

2. Occupational Health Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy

3. Center of Functional Genomics and Rare Diseases, Buzzi Children’s Hospital, 20154 Milan, Italy

4. Unit of Medical Statistics, Bioinformatics and Epidemiology, Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, 20133 Milan, Italy

5. Dipartimento di Scienze Biomediche per la Salute, University of Milan, 20133 Milan, Italy

6. U. O. Laboratorio Morfologia Umana Applicata, IRCCS Policlinico San Donato, 20097 Milan, Italy

Abstract

Intercellular communication has been transformed by the discovery of extracellular vesicles (EVs) and their cargo, including microRNAs (miRNAs), which play crucial roles in intercellular signaling. These EVs were previously disregarded as cellular debris but are now recognized as vital mediators of biological information transfer between cells. Furthermore, they respond not only to internal stimuli but also to environmental and lifestyle factors. Identifying EV-borne oncomiRs, a subset of miRNAs implicated in cancer development, could revolutionize our understanding of how environmental and lifestyle exposures contribute to oncogenesis. To investigate this, we studied the plasma levels of EV-borne oncomiRs in a population of 673 women and 238 men with a body mass index > 25 kg/m2 (SPHERE population). The top fifty oncomiRs associated with the three most common cancers in women (breast, colorectal, and lung carcinomas) and men (lung, prostate, and colorectal carcinomas) were selected from the OncomiR database. Only oncomiRs expressed in more than 20% of the population were considered for statistical analysis. Using a Multivariate Adaptive Regression Splines (MARS) model, we explored the interactions between environmental/lifestyle exposures and EV oncomiRs to develop optimized predictor combinations for each EV oncomiR. This innovative approach allowed us to better understand miRNA regulation in response to multiple environmental and lifestyle influences. By uncovering non-linear relationships among variables, we gained valuable insights into the complexity of miRNA regulatory networks. Ultimately, this research paves the way for comprehensive exposome studies in the future.

Funder

European Research Council

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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