# Exploring microRNA degradation in T-cell acute lymphoblastic leukemia

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2024 · $81,624

## Abstract

PROJECT SUMMARY
Gene expression, the flow of genetic information from DNA to messenger RNA (mRNA) to protein,
involves delicate regulation by a group of small RNAs named microRNAs. MicroRNAs can inhibit gene
expression by binding to mRNAs and prevent them from being translated into proteins. MicroRNA
levels in cancer cells are usually different from the microRNA levels in healthy cells, leading to
differential expression of certain cancer-related genes. Controlling microRNA levels therefore offers a
promising target for cancer treatment.
Recently, we found that when T-cell acute lymphoblastic leukemia (T-ALL) cells are treated with
dexamethasone, a glucocorticoid steroid commonly used in leukemia chemotherapy, two highly related
and pro-cancer microRNAs (miR-221/222) are degraded by their target mRNA (BIM). This is surprising
because microRNAs usually control the levels of their targets, but not the other way around. This is also
exciting because it represents an emerging gene regulation mode carried out by the mRNAs and opens
up strategies for cancer intervention.
In this proposal, we first aim to understand how BIM mRNA triggers miR-221/222 degradation. Our
second aim is to explore how miR-221/222 degradation enhances killing of T-ALL cells during
chemotherapy. In the final aim, we will develop an innovative biochemical and computational protocol to
globally identify sequences in different target mRNAs that can induce miRNA degradation in T-ALL
patient samples.
Collectively, our efforts will examine a new mechanism of gene regulation in T-ALL, in which mRNAs
counteract microRNAs. Because resistance to glucocorticoid is a serious limitation for T-ALL
chemotherapy, elucidating the underlying mechanism of resistance may provide the basis for improving
current therapeutic interventions. Given that we have discovered a potentially widespread occurrence
of the mRNA-induced microRNA degradation pathway in cancer, identifying the mRNAs that can
degrade miRNAs and the proteins involved in this process would help develop new therapies to combat
T-ALL.

## Key facts

- **NIH application ID:** 11059702
- **Project number:** 3R01CA282812-02S1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Jonathan D. Licht
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $81,624
- **Award type:** 3
- **Project period:** 2023-07-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11059702

## Citation

> US National Institutes of Health, RePORTER application 11059702, Exploring microRNA degradation in T-cell acute lymphoblastic leukemia (3R01CA282812-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11059702. Licensed CC0.

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