Department of Animal Medicine, Production and Health, University of Padova, 35020 Legnaro, Italy.
IRCAN, CNRS, INSERM, Université Côte d'Azur, 06107 Nice, France.
Genes (Basel). 2022 Jun 10;13(6):1046. doi: 10.3390/genes13061046.
Aging is one of the hallmarks of multiple human diseases, including cancer. We hypothesized that variations in the number of copies (CNVs) of specific genes may protect some long-living organisms theoretically more susceptible to tumorigenesis from the onset of cancer. Based on the statistical comparison of gene copy numbers within the genomes of both cancer-prone and -resistant species, we identified novel gene targets linked to tumor predisposition, such as CD52, SAT1 and SUMO. Moreover, considering their genome-wide copy number landscape, we discovered that microRNAs (miRNAs) are among the most significant gene families enriched for cancer progression and predisposition. Through bioinformatics analyses, we identified several alterations in miRNAs copy number patterns, involving miR-221, miR-222, miR-21, miR-372, miR-30b, miR-30d and miR-31, among others. Therefore, our analyses provide the first evidence that an altered miRNAs copy number signature can statistically discriminate species more susceptible to cancer from those that are tumor resistant, paving the way for further investigations.
衰老是多种人类疾病的特征之一，包括癌症。我们假设，特定基因的拷贝数变异（CNVs）数量的差异可能会保护一些理论上更容易发生肿瘤发生的长寿生物体免受癌症的侵袭。基于对易患癌症和抗癌症物种基因组中基因拷贝数的统计比较，我们确定了与肿瘤易感性相关的新的基因靶标，如 CD52、SAT1 和 SUMO。此外，考虑到它们的全基因组拷贝数景观，我们发现 microRNAs（miRNAs）是最显著的富含癌症进展和易感性的基因家族之一。通过生物信息学分析，我们确定了 miRNA 拷贝数模式的几个改变，涉及 miR-221、miR-222、miR-21、miR-372、miR-30b、miR-30d 和 miR-31 等。因此，我们的分析首次提供了证据，表明改变的 miRNAs 拷贝数特征可以从那些具有肿瘤抗性的物种中统计学上区分出更容易患癌症的物种，为进一步的研究铺平了道路。
