Long Noncoding RNAs in Cancer Pathways

Abstract

Genome-wide cancer mutation analyses are revealing an extensive landscape of functional mutations within the noncoding genome, with profound effects on the expression of long noncoding RNAs (lncRNAs). While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, we now understand that lncRNAs drive many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein, and RNA. Recent advancements in surveying lncRNA molecular mechanisms are now providing the tools to functionally annotate these cancer-associated transcripts, making these molecules attractive targets for therapeutic intervention in the fight against cancer.

Figure 1. LncRNA mechanisms rely on interactions with cellular macromolecules

(A) Chromatin bound lncRNAs can regulate gene expression by controlling local chromatin architecture (above) or directing the recruitment of regulatory molecules to specific loci (below). (B) LncRNA interactions with multiple proteins can promote the assembly of protein complexes (above), or impair protein-protein interactions (below). (C) mRNA interactions with lncRNA can recruit protein machinery involved in multiple aspects of mRNA metabolism to affect splicing, mRNA stability, or translation (above) or sequester miRNA away from target mRNA (below).

Figure 2. LncRNAs in Cancer Phenotypes

LncRNAs contribute to each of the six hallmarks of cancer (diagram adapted from Hanahan and Weinberg, 2000). Selected examples of lncRNAs and their molecular partners or genomic targets are shown for proliferation, growth suppression, motility, immortality, angiogenesis, and viability cancer phenotypes.