For cis-elements, it is believed the sequences upstream and downstream of circRNAs are critical for its formation and among them, Alu repeats and reverse complementary matches (RCMs) have been well documented.19, 31, 32, 33 Regarding the trans-factors, we successfully linked a formerly reported negative regulator, ADAR1, with AR in HCC and elucidated the source of circRNA expression bias.19 Another RNA-binding protein, QKI, seems not to participate in the AR-related biogenesis of circRNAs based on our data.33 This evidence concerns the gene AR and hepatocellular carcinoma.