# The role of FENDRR in host defense against Mycobacterium tuberculosis infection

> **NIH NIH R01** · OKLAHOMA STATE UNIVERSITY STILLWATER · 2022 · $578,995

## Abstract

PROJECT SUMMARY
Mycobacterium tuberculosis (M.tb) is an intracellular bacterial pathogen that causes tuberculosis in humans.
Tuberculosis remains a major global public health threat. Annually, there are approximately 10 million active
tuberculosis cases and 1.4 million deaths worldwide. The mechanism of host-M.tb interactions remains to be
defined. Long noncoding RNAs (lncRNAs) are noncoding transcripts longer than 200 nucleotides. In response
to bacterial infections, mammalian cells produce abundant lncRNAs to mediate host-pathogen interactions,
which are beneficial or detrimental to host defense. A very limited number of studies have been reported on the
role of host lncRNAs in the response to M.tb infection. However, increasing evidence indicates that host lncRNAs
are engaged in the host defense against microbial infection in host cells. Our long-term goals are to elucidate
the fundamental mechanisms of the host lncRNA-regulated anti-M.tb response in macrophages and investigate
the potential application of host lncRNAs as novel host-directed therapies for tuberculosis. Our preliminary data
indicate that M.tb infection induces the expression of host lncRNA, fetal-lethal noncoding development regulatory
RNA (FENDRR), in mouse and human macrophages in vitro and in vivo. Additionally, FENDRR-knockdown
facilitates M.tb growth in mouse and human macrophages in cell culture. Furthermore, FENDRR interacts with
host iron-responsive element-binding protein 1(Irp1) and down-regulates host microRNA miR-214 in mouse
macrophages post M.tb infection. We hypothesize that FENDRR mediates the anti-M.tb response by controlling
intracellular iron availability via interfering with iron-responsive protein IRP1 and by upregulating the anti-M.tb
protein enhancer of Zeste homolog 1 (EZH1) through competing with the host microRNA miR-214. We will test
our hypothesis using mouse and human macrophage cell culture, and mouse models of tuberculosis. Aim I will
investigate the mechanism by which M.tb induces FENDRR expression via the TLR2-Myd88-p38-C/EBPβ axis.
Aim II will define the mechanisms by which FENDRR exerts anti-M.tb response. Aim III will evaluate the
functional roles and mechanisms of action of FENDRR in mouse models of tuberculosis. The proposed studies
will reveal a novel anti-M.tb pathway mediated by host lncRNA FENDRR.

## Key facts

- **NIH application ID:** 10559243
- **Project number:** 1R01AI173180-01
- **Recipient organization:** OKLAHOMA STATE UNIVERSITY STILLWATER
- **Principal Investigator:** Yong Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $578,995
- **Award type:** 1
- **Project period:** 2022-09-21 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10559243

## Citation

> US National Institutes of Health, RePORTER application 10559243, The role of FENDRR in host defense against Mycobacterium tuberculosis infection (1R01AI173180-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10559243. Licensed CC0.

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