# RNA oxidation in RAS-driven cancer

> **NIH NIH R21** · ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED · 2024 · $396,654

## Abstract

ABSTRACT
Chemical modifications in RNA play a crucial role in regulating gene expression in physiological and pathological
conditions. One underexplored aspect of this regulation comes from reactive oxidative species (ROS), which
modify nucleobases in RNA. Elevated levels of ROS and oxidative stress are prevalent in cancer cells, resulting
from metabolic reprogramming and driven by factors such as activated RAS expression. However, our
understanding of how ROS-induced RNA modifications affect gene expression in a cancer context remains
limited. This study aims to fill this knowledge gap by exploring the roles and regulatory implications of oxidative
modifications of RNA, with a focus on KRAS-driven redox perturbations in non-small cell lung cancer cells. The
project has two main objectives. The first objective is to identify the patterns of oxidative modifications in RNA
induced by oncogenic KRAS. This will be achieved through the combination of next-generation sequencing
techniques and chemical methods to create high-resolution profiles of 8-oxoguanine modifications in RNA. The
second objective is to understand the molecular players that ‘read’ these modifications. This will be done through
biochemical and CLIP analysis techniques, focusing on proteins from the heterogeneous nuclear
ribonucleoprotein (hnRNP) family. By elucidating these interactions, the study aims to uncover potential
influences of oxidative RNA modifications on gene expression changes in cancer cells. The outcomes of this
study will significantly contribute to our fundamental understanding of gene regulation in cancer. Since oxidative
stress is a hallmark of many pathological states, the technological and conceptual advancements made in this
study will also have broader relevance in understanding the role of oxidative RNA modifications in the
pathogenesis of diseases.

## Key facts

- **NIH application ID:** 10951216
- **Project number:** 1R21CA293416-01
- **Recipient organization:** ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED
- **Principal Investigator:** DIMITRI G PESTOV
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $396,654
- **Award type:** 1
- **Project period:** 2024-06-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951216

## Citation

> US National Institutes of Health, RePORTER application 10951216, RNA oxidation in RAS-driven cancer (1R21CA293416-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10951216. Licensed CC0.

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