State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
Nat Commun. 2024 Feb 15;15(1):1401. doi: 10.1038/s41467-024-45767-1.
Mammals exhibit different rates of cancer, with long-lived species generally showing greater resistance. Although bats have been suggested to be resistant to cancer due to their longevity, this has yet to be systematically examined. Here, we investigate cancer resistance across seven bat species by activating oncogenic genes in their primary cells. Both in vitro and in vivo experiments suggest that Myotis pilosus (MPI) is particularly resistant to cancer. The transcriptomic and functional analyses reveal that the downregulation of three genes (HIF1A, COPS5, and RPS3) largely contributes to cancer resistance in MPI. Further, we identify the loss of a potential enhancer containing the HIF1A binding site upstream of COPS5 in MPI, resulting in the downregulation of COPS5. These findings not only provide direct experimental evidence for cancer resistance in a bat species but also offer insights into the natural mechanisms of cancer resistance in mammals.
哺乳动物的癌症发病率不同，通常寿命较长的物种具有更强的抵抗力。尽管蝙蝠由于寿命长而被认为具有抗癌能力，但这尚未得到系统的研究。在这里，我们通过激活七种蝙蝠主要细胞中的致癌基因来研究抗癌能力。体内外实验均表明，蹄蝠（Myotis pilosus，MPI）对癌症具有特别强的抵抗力。转录组和功能分析表明，三个基因（HIF1A、COPS5 和 RPS3）的下调在很大程度上导致了 MPI 的抗癌能力。此外，我们发现 MPI 中 COPS5 上游的 HIF1A 结合位点上游缺失了一个潜在的增强子，导致 COPS5 的下调。这些发现不仅为蝙蝠物种的抗癌能力提供了直接的实验证据，也为哺乳动物的抗癌天然机制提供了新的见解。
