E2F4 and urinary bladder cancer: A previous study found that the CpG122 and CpG74 hypermethylation in the promoter region of HAND2-AS1 led to its low expression.[23] In bladder cancer, the HAND2-AS1/miR-146/RARB complex could promote Caspase 3-mediated apoptosis by suppressing COX-2 expression.[13] Gong et al[22] reported HAND2-AS1 could attenuate cell proliferation, migration, invasion, and tumorigenesis of cervical cancer by downregulating C16orf74 expression through recruiting E2F4.