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Can Circular RNA Block Melanoma Metastasis?

By: Lauren Harrison, MS
Posted: Thursday, March 5, 2020

Through investigation into the role of circular RNA (circRNA), researchers found a functional, prognostic, and predictive role for cerebellar degeneration–related 1 antisense (CDR1as) in the progression of melanoma. Although the function of circRNA is still unclear, Eva M. Hernando, PhD, of New York University Grossman School of Medicine, New York, and colleagues believe that instead of encoding proteins, circRNA may be part of complex regulatory systems. Their findings were published in Cancer Cell.

“Our study provides new insights into melanoma aggressive behavior and is the first to expose a circRNA as a suppressor of metastasis,” said Dr. Hernando in an NYU Langone Health press release.

Profiling of circRNA was employed to identify CDR1as as a potential suppressor of melanoma, which was confirmed when its expression was found to be downregulated in progressive melanoma. In addition, CDR1as was found to arise from a long noncoding RNA, and this gene locus appears to be epigenetically silenced in melanoma. Researchers modeled CDR1as loss in melanoma cells in vitro and saw that depletion of this gene did lead to enhanced invasion, although no change in cell growth. This same effect was seen when using an in vivo mouse model for CDR1as knockdown.

Furthermore, the researchers investigated the role of CDR1as as a suppressor of metastasis and found that CDR1as depletion had no effect on miR-7-5-p abundance in melanoma cells, despite the fact that CDR1as interacts with miR-7 through conserved binding sites. However, the oncofetal protein family IGF2BP, which regulates several mRNA transcripts, was found to interact with CDR1as. The silencing of IGF2BP3 abolished the induction of invasion that is mediated by CDR1as depletion.

“We found CDR1as restrains a known procancer protein called IGF2BP3, revealing a new function of CDR1as that may have therapeutic implications,” commented first author Douglas S. Hanniford, PhD, also of NYU Grossman School of Medicine.

Disclosure: The research was funded by the Melanoma Research Alliance and the National Institutes of Health. The authors reported no conflicts of interest.

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