Direct targeting of CDH11 mRNA by microRNA miR-451a was demonstrated in mouse, via a luciferase assay. Both miR-451a and the 3'UTR of CDH11 that miR-451a is predicted to bind to are conserved between human and mouse (Wang et al. 2020). Transfection of miR-451a into human bronchoepithelial cell line 116HBE results in reduction of CDH11 mRNA levels (Wang et al. 2020). Downregulation of CDH11 mRNA was observed in renal cancer cell lines transfected by miR-451a (Yamada et al. 2018). Expression levels of miR-451a and CDH11 mRNA are inversely correlated in CD4+ T lymphocytes of children with asthma (Wang et al. 2021).

As the 3'UTR is conserved between the two human CDH11 splicing isoforms, both mRNA isoforms are shown as targets of miR-451a, with the short variant, not present in mouse, annotated as a set candidate. Since miR-451a was shown to reduce CDH11 mRNA level in both human and mice, the miR-451a endonucleolytic RISC is annotated as a set member of the miR-451a RISC set, while the miR-451a nonendonucleolytic RISC is annotated as a set candidate. (Footnote: Two versions of RNA-induced silencing complex, RISC, exist: endonuleolytic and nonendonucleolytic. Endonucleolytic RISC cleaves the target mRNA, leading to reduction in both mRNA and protein levels. Nonendonuleolytic RISC does not cleave the target mRNA, but still interferes with translation, leading to reduced protein level of the target gene, but no change in the mRNA level. If the study Reactome is citing shows reduction of mRNA level off the target in the presence of miRNA, the involvement of an endonucleolytic RISC is certain. Hence, the endonucleolytic RISC is annotated either on its own if the involvement of a nonendonucleolytic RISC can be excluded, or as a set member if the involvement of a nonendonucleolytic RISC cannot be excluded. In the latter case, which is the most frequent scenario encountered in published studies, the corresponding nonendonucleolytic RISC is annotated as a candidate. If the experimental results show decreased protein level of the miRNA target gene but no change in the mRNA level, than only a nonendonucleolytic RISC is annotated. Please refer to the pathway "Gene Silencing by RNA" for additional details.)