Challenging paradigms: long non-coding RNAs in breast ductal carcinoma in situ (DCIS)
OVERVIEW The continuing challenges to the treatment of breast ductal carcinoma in situ (DCIS) warrant a new avenue of investigation. In parallel, a startling revelation of the first post-genomic decade has been the rising prominence of long non-coding RNAs (lncRNAs) as key gene regulators, including in breast cancer. High-throughput experimental surveys of the human transcriptome show that lncRNAs are abundant. In contrast to microRNAs (miRNAs), lncRNAs possess multiple, diverse, heterogeneous molecular mechanisms of action making them high-level master regulators of gene regulatory networks and pathways in cancer. In particular, lncRNAs directly regulate the activity of transcription proteins and epigenetic modifiers, which, in turn, govern their own downstream sets of target genes. Therefore, provided that such lncRNA regulatory activities are functional in cancer, including DCIS, targeting the lncRNAs or the regulatory networks which they mediate can represent an important new avenue of treatment. Development of lncRNAtargeting therapies may emerge into a key innovation generated in clinical and translational research by the innovative use of the latest human genome annotation datasets combined with high throughput transcriptome analyses. We propose a paradigm shift: direct interrogation of lncRNAs in the molecular characterization of DCIS subtypes, including the idea that lncRNAs may be the trigger for progression from in situ to invasive cancer.