Functional Modulation of Gene Expression by Ultraconserved Long Non-coding RNA TUC338 during Growth of Human Hepatocellular Carcinoma

TUC338 is an ultraconserved long non-coding RNA that contributes to transformed cell growth in hepatocellular carcinoma (HCC). Genomic regions of TUC338 occupancy were enriched in unique or known binding motifs homologous to the tumor suppressors Pax6 and p53. Genes involved in cell proliferation were enriched within a 9-kb range of TUC338-binding sites. TUC338 RNA-based purification was used to isolate chromatin for mass spectrometry, and the plasminogen activator inhibitor-1 RNA-binding protein (PAI-RBP1) was identified as a TUC338 RNA-binding partner. The PAI-RBP1 target gene plasminogen activator inhibitor-1 (PAI-1) itself could also be post-transcriptionally regulated by TUC338. Thus modulation of transformed cell growth by TUC338 may involve binding to PAI-RBP1 as well as to sequence-defined cis-binding sites to modulate gene expression. These findings suggest that ultraconserved RNAs such as TUC338 can function in a manner analogous to transcription factors to modulate cell proliferation and transformed cell growth in HCC.