# Role of circular RNA CDR1as in melanoma

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $549,348

## Abstract

Cutaneous melanoma is a highly aggressive tumor type with rising incidence. Despite remarkable therapeutic
advances in recent years, metastatic melanoma remains a lethal disease for thousands of patients each year,
thus new treatments are still needed. Overcoming this challenge requires deep knowledge of the underlying
biology driving and sustaining melanoma metastasis.
We are studying a novel type of RNA species, circular RNA (circRNA), which are covalently ligated RNA loops
arising from cis back-splicing. We have observed that expression of the circRNA CDR1as is lost in melanoma
cell lines and patient tissues. In primary melanoma patient tissues, loss of CDR1as strongly associates with poor
patient outcomes, suggesting its loss may be a driver of melanoma progression. Modeling CDR1as silencing,
shRNA-mediated depletion of CDR1as enhanced invasion and metastasis of melanoma cells in xenograft
models. The precise mechanism(s) by which CDR1as silencing effects a pro-tumorigenic phenotype of
melanoma cells remains undetermined. Initial publications suggested CDR1as functions as an endogenous
inhibitor of the microRNA miR-7 in neurons. Surprisingly, in melanoma, we did not observe clear regulation of
miR-7 expression or function after depletion of CDR1as, suggesting it has additional functions. We have
preliminary data supporting a role for novel CDR1as interacting proteins, including members of the IGF2BP
family, which are known to be pro-tumorigenic in a variety of cancer contexts.
Our goals with this proposal are the following: Taking a candidate approach, we plan to dissect the contribution(s)
of the IGF2BP proteins to the functional consequences of CDR1as silencing in melanoma cells. In addition, we
plan to perform a set of unbiased analyses, such as RNA-seq, RIBO-seq, RNA pull downs and proteomic
profiling, to comprehensively examine possible mechanism(s) regulated by CDR1as silencing, downstream or
independent of IGF2BPs. We will use in vitro, xenograft models and genetically engineered mouse models
(GEMMs) to elucidate the biological processes, pathways and molecules controlled by CDR1as during
melanoma progression. Our studies might uncover novel therapeutic targets or strategies to exploit for
melanoma patient treatment.

## Key facts

- **NIH application ID:** 9998546
- **Project number:** 1R01CA243446-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Eva Hernando
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $549,348
- **Award type:** 1
- **Project period:** 2020-03-02 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998546

## Citation

> US National Institutes of Health, RePORTER application 9998546, Role of circular RNA CDR1as in melanoma (1R01CA243446-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9998546. Licensed CC0.

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