Abstract
Over the past few years, small non-coding RNAs (smRNAs) have emerged as major regulators of metastatic progression. While micro-RNAs were among the first characterized post-transcriptional regulators of metastasis, we have now demonstrated that other annotated smRNAs, such as tRNAs and tRNA fragments, also impact metastatic progression. In their capacity as master regulators of gene expression, smRNAs play a major role in development, normal cell physiology, and homeostasis. However, they are often co-opted by cancer cells to help reprogram their gene expression landscape as the disease progresses. Our group has recently discovered a new class of small RNAs, which we have named orphan non-coding RNAs or oncRNAs [Fish et al, Nature Med 2018], that are largely undetected in normal cells and tissues and emerge as a consequence of cellular transformation. Because they were not previously annotated, oncRNAs had gone unnoticed in prior studies by us and others that were instead focused on quantitative changes in the expression of common smRNA regulators, such as miRNAs and tRNA fragments. These oncRNAs, which we first identified in breast cancer, provide a pool of new biomolecules with regulatory potential that can be subsequently adopted by tumor cells to carry out new oncogenic functions. We have demonstrated that breast cancer cells adopt a specific oncRNA (named T3p) to regulate the expression of two key promoters of metastasis. This finding demonstrates that oncRNAs can serve as potential building blocks for “cancer-emergent” regulatory pathways. We posit that oncRNA-mediated regulatory interactions add a new layer of complexity to gene regulation in cancers.