Experimental evidence for cancer resistance in a bat species

Here we investigate cancer resistance across seven bat species by activating oncogenic Ras and SV40 LT in their fibroblasts. The experimental results of anchorage-independent growth in vitro and tumor xenografts in vivo consistently suggest cancer resistance in a bat species Myotis pilosus (MPI). By comparative transcriptomic analyses, we identify three downregulated genes (HIF1A, COPS5, and RPS3) in MPI and the silence of their expression inhibits tumor cell proliferation. Using a gene-reporter assay, we demonstrate that a potential enhancer containing the HIF1A binding site upstream of COPS5 is lost in MPI, which could downregulate the COPS5 expression. When the expression of COPS5 is inhibited, mouse cells become unsusceptible to malignant transformation to form tumors in vivo. Together, our findings provide direct experimental evidence for cancer resistance in a bat species and offer new insights into the natural mechanisms of cancer resistance.Tips:The big-footed bat (dazushuerfu;MPI for short), the Szechwan myotis (xinan;MAL), the least horseshoe bat (xiaojutou;RPU), the greater horseshoe bat (matiejutoufu;RFE), the Chinese rufous horseshoe bat (zhonghuajutoufu;RSI), the great leaf-nosed bat (dadifu;HAR), and the Leschenault's Rousette (zongguofu;RLE), as well as laboratory mouse (MLF)