Clinical applications of lncRNAs

The central dogma that forms the backbone of molecular biology is that DNA codes for RNA (transcription) which then codes for proteins (translation). However, studies over the last few years demonstrated that just 1.5% of the 3 billion base pairs of DNA constituting the human genome generate the ~20,000 protein coding genes, whereas at least 90% of genome is transcribed into non-coding RNA (ncRNA) that does not result in a protein product. The rapid characterization of numerous ncRNAs has dramatically altered our understanding of biology. The discovery of long ncRNAs (lncRNAs, longer than 200 nucleotides) as mediators of various cellular processes as well as various human pathophysiologic processes including cancer has established their role as critical biological entities. Several lncRNAs have been linked to oncogenesis; for example, HOTAIR in breast and colon cancer, and SChLAP1, PCAT-1 and ANRIL in prostate cancer. SChLAP1 in situ hybridization (RNA-ISH) has been recently demonstrated by our group to be a novel tissue-based biomarker assay for outcome prognostication after radical prostatectomy that carries great clinical promise to help direct risk stratification for patients with prostate cancer. Because RNA-ISH assay is evaluated using a light microscope, it not only allows detection of lncRNA of interest, it provides insight into the localization of the lncRNA as well. Overall, a myriad of lncRNAs are associated with carcinogenesis and RNA-ISH provides a practical tool for clinical application of lncRNA markers of interest in situ.