Since the discovery of
microRNAs, non-coding RNAs (NC-RNAs) have increasingly attracted the attention of
cancer investigators. Two classes of NC-RNAs are emerging as putative
metastasis-related genes: long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs). LncRNAs orchestrate metastatic progression through several mechanisms, including the interaction with epigenetic effectors, splicing control and generation of
microRNA-like molecules. In contrast, snoRNAs have been long considered "housekeeping" genes with no relevant function in
cancer. However, recent evidence challenges this assumption, indicating that some snoRNAs are deregulated in
cancer cells and may play a specific role in
metastasis. Interestingly, snoRNAs and lncRNAs share several mechanisms of action, and might synergize with
protein-coding genes to generate a specific cellular phenotype. This evidence suggests that the current paradigm of metastatic progression is incomplete. We propose that NC-RNAs are organized in complex interactive networks which orchestrate cellular phenotypic plasticity. Since plasticity is critical for
cancer cell
metastasis, we suggest that a molecular interactome composed by both NC-RNAs and
proteins orchestrates
cancer metastasis. Interestingly, expression of lncRNAs and snoRNAs can be detected in
biological fluids, making them potentially useful
biomarkers. NC-
RNA expression profiles in human
neoplasms have been associated with patients' prognosis.
SnoRNA and
lncRNA silencing in pre-clinical models leads to
cancer cell death and/or
metastasis prevention, suggesting they can be investigated as novel therapeutic targets. Based on the literature to date, we critically discuss how the NC-
RNA interactome can be explored and manipulated to generate more effective diagnostic, prognostic, and therapeutic strategies for metastatic
neoplasms.