miRNAs Copy Number Variations repertoire as hallmark indicator of cancer species predisposition

Abstract

Aging is one of the hallmarks of multiple human diseases, including cancer. However, the molecular mechanisms associated with high longevity and low cancer incidence percentages characterizing long-living organisms have not been fully understood yet. In this context, we hypothesized that variations in the number of copies (CNVs) of specific genes may protect some species from cancer onset. Based on the statistical comparison of gene copy numbers within the genomes of cancer -prone and -resistant organisms, we identified novel gene targets linked to the tumor predisposition of a species, such as CD52, SAT1 and SUMO protein family members. Furthermore, for the first time, we were able to discover that, considering the entire genome copy number landscape of a species, microRNAs (miRNAs) are among the most significant gene families enriched for cancer progression and predisposition. However, their roles in ageing and cancer resistance from a comparative perspective remains largely unknown. To this end, we identified through bioinformatics analysis, several alterations in miRNAs copy number patterns, represented by duplication of miR-221, miR-222, miR-21, miR-372, miR-30b, miR-30d and miR-31 among others. Therefore, our analysis provides the first evidence that an altered copy number miRNAs signature is able to statistically discriminate species more susceptible to cancer than those that are tumor resistant, helping researchers to discover new possible therapeutic targets involved in tumor predisposition.