# Circle RNA Regulation of Lung Cancer Metastasis

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $360,511

## Abstract

Lung cancer is the leading cause of cancer-related deaths in the U.S., accounting for about 132,000 deaths per
year. While targeted therapies of lung adenocarcinoma have improved overall survival, similar advances in lung
squamous carcinoma (LUSC) have been stagnant. Extensive molecular profiling through the Cancer Genome
Atlas (TCGA) effort revealed that LUSC tumors are highly idiosyncratic and rarely driven by solitary actionable
pathways. Also, metastasis, rather than primary tumors, is responsible for the majority of cancer-related deaths.
However, the mechanistic underpinnings of how LUSC spreads are very poorly understood. In this proposal, we
will investigate the roles of a circle RNA (circRNA), CDR1as, on its regulation of LUSC metastasis. To investigate
the regulatory role of CDR1as on LUSC metastasis, we have recently developed sophisticated LUSC models
that metastasize to sites common to human disease. By integrating clinical LUSC TCGA data with our mouse
models, we have identified CDR1as as a key driver of LUSC metastasis. We have found that CDR1as plays a
key role in stabilizing the coding mRNA transcript for cerebellar degeneration-related protein 1 (CDR1). We found
that CDR1as and CDR1 are each necessary for LUSC metastasis, and CDR1 over-expression alone is sufficient
to promote LUSC metastasis. We found CDR1 interacts with several specific Golgi trafficking proteins, and CDR1
expression corresponds with poor LUSC survival and tightly couples with an epithelial-mesenchymal transition
(EMT) program. Additionally, we have found key structural elements of CDR1as that promote its RNA stability
and expression levels. Taken together, key questions arise, such as: 1) How does CDR1 trafficking in the Golgi
vesicles promote migration and metastasis? 2) Can oligo-mediated targeting of CDR1as block LUSC metastasis
and prolong survival? The objectives of this proposal are to define how CDR1 promotes LUSC metastasis
through Golgi trafficking. We will also determine the biologic and therapeutic implications of interrupting structural
elements of CDR1as.

## Key facts

- **NIH application ID:** 10820428
- **Project number:** 5R01CA279532-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Chad V Pecot
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $360,511
- **Award type:** 5
- **Project period:** 2023-04-04 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820428

## Citation

> US National Institutes of Health, RePORTER application 10820428, Circle RNA Regulation of Lung Cancer Metastasis (5R01CA279532-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10820428. Licensed CC0.

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