Circular RNAs (circRNAs) are a subclass of noncoding RNAs widely expressed in 
mammalian cells. We report here the tumorigenic capacity of a circRNA derived 
from angiomotin-like1 (circ-Amotl1). Circ-Amotl1 is highly expressed in patient 
tumor samples and cancer cell lines. Single-cell inoculations using 
circ-Amotl1-transfected tumor cells showed a 30-fold increase in proliferative 
capacity relative to control. Agarose colony-formation assays similarly revealed 
a 142-fold increase. Tumor-take rate in nude mouse xenografts using 6-day (219 
cells) and 3-day (9 cells) colonies were 100%, suggesting tumor-forming 
potential of every cell. Subcutaneous single-cell injections led to the 
formation of palpable tumors in 41% of mice, with tumor sizes >1 cm3 in 1 month. 
We further found that this potent tumorigenicity was triggered through 
interactions between circ-Amotl1 and c-myc. A putative binding site was 
identified in silico and tested experimentally. Ectopic expression of 
circ-Amotl1 increased retention of nuclear c-myc, appearing to promote c-myc 
stability and upregulate c-myc targets. Expression of circ-Amotl1 also increased 
the affinity of c-myc binding to a number of promoters. Our study therefore 
reveals a novel function of circRNAs in tumorigenesis, and this subclass of 
noncoding RNAs may represent a potential target in cancer therapy.