The pseudogene TUSC2P promotes TUSC2 function by binding multiple microRNAs

Various non-coding regions of the genome, once presumed to be 'junk' DNA, have recently been found to be transcriptionally active. In particular, pseudogenes are now known to have important biological roles. Here we report that transcripts of the two tumour suppressor candidate-2 pseudogenes (TUSC2P), found on chromosomes X and Y, are homologous to the 3'-UTR of their corresponding protein coding transcript, TUSC2. TUSC2P and the TUSC2 3'-UTR share many common miRNA-binding sites, including miR-17, miR-93, miR-299-3p, miR-520a, miR-608 and miR-661. We find that ectopic expression of TUSC2P and the TUSC2 3'-UTR inhibits cell proliferation, survival, migration, invasion and colony formation, and increases tumour cell death. By interacting with endogenous miRNAs, TUSC2P and TUSC2 3'-UTR arrest the functions of these miRNAs, resulting in increased translation of TUSC2. The TUSC2P and TUSC2 3'-UTR could thus be used as combinatorial miRNA inhibitors and might have clinical applications.