A hybrid approach to assess the structural impact of long  noncoding RNA mutations uncovers key NEAT1 interactions in colorectal cancer

AbstractLong noncoding RNAs (lncRNAs) are emerging players in cancer and they entail potential as prognostic biomarkers or therapeutic targets. Earlier studies have identified somatic mutations in lncRNAs that are associated with tumor relapse after therapy, but the underlying mechanisms behind these associations remain unknown. Given the relevance of secondary structure for the function of some lncRNAs, some of these mutations may have a functional impact through structural disturbance. Here, we examined the potential structural and functional impact of a novel A  >  G point mutation inNEAT1 that has been recurrently observed in tumors of colorectal cancer patients experiencing relapse after treatment. Here, we used the nextPARS structural probing approach to provide first empirical evidence that this mutation altersNEAT1 structure. We further evaluated the potential effects of this structural alteration using computational tools and found that this mutation likely alters the binding propensities of severalNEAT1-interacting miRNAs. Differential expression analysis on these miRNA networks shows upregulation ofVimentin, consistent with previous findings. We propose a hybrid pipeline that can be used to explore the potential functional effects of lncRNA somatic mutations.
Source: IUBMB Life - Category: Research Authors: Tags: SPECIAL ISSUE Source Type: research