# The importance of viral and host circular non-coding RNAs in human papillomavirus-related cancers

> **NIH NIH P20** · WEST VIRGINIA UNIVERSITY · 2020 · $259,442

## Abstract

PROJECT SUMMARY/ABSTRACT 
Although recent findings have shown the importance of the newly discovered circular non-coding RNAs 
(circRNAs) in the process carcinogenesis, studies showing the expression of circRNAs by oncogenic viruses or 
the potential regulation of human circRNAs by this type of viruses have not been described. Our preliminary 
findings suggest the discovery of two viral circRNAs expressed by the high-risk Human Papillomavirus type 16 
(HPV-16) and type 18 (HPV-18) in cervical cancer (CaCx) and head and neck cancer (HNSCC) cell lines (the 
first example of circular RNAs produce by DNA viruses). These viral circRNAs (hpv-circK and hpv-circD) are 
localized in the nucleus of HPV-positive cells suggesting a role in transcription regulation. Furthermore, 
knockdown of hpv16-circK reduces cellular proliferation in HPV-positive cells and overexpression of this viral 
circRNA increases proliferation. Additionally, we found that expression of HPV-16 oncoprotein E6 is able to 
change the global expression of human circRNAs in primary human cells. Some of these circRNAs such as 
circGSK3B, circMYBL2 and circFN1 are expressed from alternative splicing regions of genes involved in cell 
metabolism, cell cycle and tumor microenvironment regulation, respectively. Our overall goal in this project is 
to analyze the newly discovered HPV-encoded circRNAs and to understand the regulation of human circRNAs 
by HPV in cancer. Finding the molecular mechanism(s) used by these circRNAs will identify new therapeutic 
targets in HPV-related cancers and in other types of malignancies. In order to identify and understand the 
importance of these viral and human circRNAs, we will utilize robust experimental models and clinical samples 
by Quantitative Real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR), RNA Fluorescence In 
Situ Hybridization (RNA FISH), Chromatin isolation by RNA Purification (ChIRP), and siRNA knockdown and 
exogenous delivery of circRNAs. The overall results will link high-risk HPV infection with the expression of viral 
or host circRNAs, contributing to a framework for the identification of new therapeutic strategies with potential 
relevance to both HPV-positive and HPV-negative cancers. This project is innovative not only because it is the 
first study describing and characterizing the expression of viral circRNAs but also because previous research 
has largely focused upon the interactions between HPV and other types of non-coding RNAs, specifically 
microRNAs and long non-coding RNAs.

## Key facts

- **NIH application ID:** 9984434
- **Project number:** 5P20GM121322-03
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Ivan Martinez
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $259,442
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984434

## Citation

> US National Institutes of Health, RePORTER application 9984434, The importance of viral and host circular non-coding RNAs in human papillomavirus-related cancers (5P20GM121322-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984434. Licensed CC0.

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