Examples of interactor elements (IEs) and structural elements (SEs) in ncRNAs. (A) The IEs from the miR-15a/miR-16 cluster target the proapoptotic oncogene BCL2. When this miRNA cluster is down-regulated in human cancer cells, the BCL2 protein is overexpressed and can be targeted by the antiapoptotic small molecule venetoclax (Croce and Reed 2016). (B) The processing of another member of the miR-16 family, miR-195, is regulated by a direct interaction with the ultraconserved ncRNA uc.283. When this lncRNA is overexpressed in human cancer due to promoter hypomethylation, this interaction prevents DROSHA cropping of the mir-195 primary transcript, leading to down-regulation of the mature miR-195, a new mechanism of tumor-suppressor microRNA inactivation (Liz et al. 2014). (C) LINC01139 (LINK-A) is the first lncRNA known to interact with lipids, specifically with PIP3, facilitating AKT activation and consequent resistance to AKT inhibitors (Lin et al. 2017). (PH-domain) Pleckstrin homology domain. (D) CCAT2 harbors a conserved SE, within which a SNP alters the secondary structure of the lncRNA so that the CCAT2 alleles bind to the CFIm splicing complex with distinct affinities. The cancer risk G allele induces the oncogenic GAC glutaminase-C isoform that causes colorectal cancer progression (Redis et al. 2016).
