# Regulation and Function of Viral and Endogenous Circular RNA in Cancer

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $557,189

## Abstract

Single-stranded circular RNAs (circRNA) are enriched in cancers, yet the regulation and biological function
of most circRNA remains unclear. Our long-term goal is to understand the role of both human
papillomavirus (HPV)-derived and endogenous circRNAs in both infectious and neoplastic diseases. The
specific goal of this proposal is to generate a more comprehensive understanding of the function and
regulation of circRNA that are present in head and neck squamous cell carcinoma (HNSCC). Our central
hypothesis is that many circRNA are coding RNA that differ in regulation and function from their
corresponding full-length RNAs in ways that promote the development of HNSCC. In preliminary studies,
we have developed innovative circRNA-Seq and Polysome RNA-Seq protocols and found that many
circRNA with coding potential are enriched in HNSCC tumors compared to adjacent non-tumor mucosa. In
addition, our discovery of HPV16 circular E7 RNA (circE7), which is translated to the E7 oncoprotein, offers
a novel tool to understand the mechanistic and physiological regulation of circRNA formation and function.
With these innovative tools and extensive preliminary evidence supporting feasibility, we propose to expand
our understanding of circRNAs in HNSCC in three related aims. First, a comprehensive transcriptomic
profile from up to 50 HPV+ and 50 HPV- HNSCC tumors and adjacent tissue will be generated, including
RNA-Seq approaches that enrich for circRNAs. Moreover, circRNA identified in this transcriptomic profiling
and circE7 will be assessed for their potential as prognostic biomarkers in a validation cohort of archived
HNSCC. Second, using the HPV16 circE7 locus, we will determine the cis and trans elements that regulate
circRNA formation in HNSCC and determine how they are physiologically regulated. Third, we will combine
HNSCC circRNA-Seq datasets with recently completed polysome RNA-Seq to identify endogenous circRNA
that are likely to be translated. These prioritized candidates will be validated and characterized through
rigorously controlled overexpression and knockdown experiments including the use of circRNA-derived
specific peptide antibodies. The investigative team includes experts in circRNA metabolism, HPV biology,
pathology, statistical genetics, head and neck cancer, and epidemiology, thus ensuring we have the skills
and resources to execute the proposal. Completion of the proposal will provide both a global and detailed
understanding of circRNA and their regulation in HNSCC.

## Key facts

- **NIH application ID:** 10877970
- **Project number:** 5R01CA275071-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Richard C Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $557,189
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877970

## Citation

> US National Institutes of Health, RePORTER application 10877970, Regulation and Function of Viral and Endogenous Circular RNA in Cancer (5R01CA275071-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10877970. Licensed CC0.

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