Long non-coding RNA UCA1 modulates chromatin remodeling via SMARCA2-containing SWI/SNF complex in human colorectal cancer
Differential lncRNA expression has been correlated to clinical characteristics of colorectal cancers (CRC), which are the second leading cause of cancer-related deaths. LncRNA UCA1 plays a role in epigenetic gene regulation in diverse cancers. We studied CRC cell properties in CRISPR/Cas9 HT29-derived models and, interestingly, UCA1-depleted HT29 cells presented an increased stem-cell phenotype. We show that loss of UCA1 modulates SWI/SNF chromatin remodeling complexes, which were previously shown to be involved in maintaining stem-cell properties. Not only was UCA1 permissive for induced SWI/SNF subunit SMARCA2 (BRM) expression upon chemo-drug treatment, but it also affected subunit compositions of SWI/SNF complexes by direct interaction of UCA1 with both ATP helicase BRM and BRG1. UCA1 is known to stimulate proliferation and decrease apoptosis, and we here show that it can restrain cells from a stem cell phenotype. The dual action of UCA1 revealed in this study highlights the complex actions of lncRNAs in cancer. Overall design: RNAseq analysis of control ICP, dUCA1E1 and dUCA1E2 cells treated for 72h with or without 2 µM 5-Fluorouracil (5-FU).