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Epigenetic Silencing of a Circular RNA Stifles Melanoma Metastasis

Epigenetic Silencing of a Circular RNA Stifles Melanoma Metastasis

ACCOUNTING for 90% of cancer-related deaths, metastasis represents a significant challenge to researchers across the oncological field. Due to its particularly aggressive and invasive nature, both in vivo and in vitro models of melanoma have been extensively researched in attempt to identify key biomarkers and therapeutic targets. Results have now emerged implicating an elusive member of the non-coding RNA family in regulating the aggressive spread of melanoma.

Circular RNA (circRNA) are covalently looped ribonucleotide sequences whose functions are in the early stages of being delineated. Potential functions include the interaction with other RNA binding proteins to regulate their function, the sponging of micro RNA to influence gene expression, or even translational capacity through retention of a genomic promoter region during transcription. Acknowledging that DNA errors cannot solely account for aggressive spread of certain cancers, a group of researchers from New York University (NYU) aimed to use cell cultures from human melanoma tissues and mouse models to determine circRNA involvement.

The investigators used epigenetic silencing of one such circRNA, CDR1as, to promote invasive properties in vitro through a micro RNA-independent mechanism; the interaction between CDR1as and an RNA-binding protein called IGF2BP3 was elucidated as being required to prevent this metastasis. Freely roaming IGF2BP3 can thus be assumed to trigger intra- and extracellular events that pre-dispose to more aggressive and invasive behaviour. “Our study provides new insights into the aggressive behaviour of melanoma, and is the first to expose a circRNA as a suppressor of metastasis,” offered senior study author Eva Hernando, an associate professor in the Department of Pathology at NYU.

Furthermore, CDR1as expression level was later seen to reflect distinct cellular states associated with various therapeutic responses. The full implications this work has for explaining the prognostic, functional, and predictive roles of circRNA in cancer research are yet to be determined. However, this study surely represents an exciting next step in discovering the true therapeutic value of non-coding RNA.