# RPMS1 circular RNAs in EBV malignancies

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $365,867

## Abstract

Summary
EBV is a human tumor virus that is an etiological agent in Hodgkin's lymphoma, non-Hodgkin's lymphomas,
stomach cancer and nasopharygeal carcinoma, and it is associated with an increased incidence of lymphomas
in the HIV-infected patient context. EBV contributes to oncogenic progression through the expression of one or
more viral genes that activate oncogenic pathways along the progression of stages that lead to cancer. A
unique aspect of herpesviruses is their utilization of “latency” gene expression programs where no virus
replication occurs and only a small subset of viral genes is expressed that remodels the host cell environment
to facilitate viral maintenance and persistence. With some of the pathways altered by latency genes
overlapping with pathway alterations required for oncogenesis, EBV latency genes are key contributors to the
tumor phenotype.
Because non-coding RNAs do not elicit adaptive immune responses, the utilization of viral non-coding RNAs in
latency settings is a key herpesviral strategy to sustain viral persistence in vivo without promoting immune
clearance. We have discovered that EBV expresses a class of largely non-coding RNAs referred to as circular
RNAs (circRNAs). Some of these circRNAs are expressed uniquely during reactivation or in distinct latency
types where they likely play roles in the corresponding stages of the EBV infection cascade. By assessing viral
circRNA expression across a broad range of cell types, latency types, reactivation, in vitro and in patient tumor
samples, we have identified a small subset of EBV circRNAs that likely play fundamental roles in EBV biology
EBV associated cancers. By performing a circRNAome analysis of the interspecies relative of EBV, the rhesus
lymphocryptovirus, we found two of these to be evolutionarily conserved, indicating evolutionary constraints on
maintaining their function. In this application, we will analyze the ubiquitiously expressed and conserved EBV
circRNA, circRPMS1_E4_E3a. Our preliminary studies show that inhibition of circRPMS1_E4_E3a leads to
decreased cell proliferation, indicating a fundamental phenotype in promoting cell growth. In this proposal, we
propose three well integrated aims that will assess the fundamental mechanisms of circRPMS1_E4_E3a's
interaction with chromatin and regulation of gene expression (aim 1), the influence of these interactions on
modulating cell signaling (aim 2), and the link between its cell signaling responses and cell growth control (aim
3).

## Key facts

- **NIH application ID:** 9938501
- **Project number:** 5R01CA243793-02
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** ERIK K FLEMINGTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,867
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938501

## Citation

> US National Institutes of Health, RePORTER application 9938501, RPMS1 circular RNAs in EBV malignancies (5R01CA243793-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9938501. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*