# Mechanism of Long Non-coding RNAs Action in leiomyoma

> **NIH NIH R01** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 2020 · $406,478

## Abstract

Uterine leiomyoma (fibroids) are benign tumors afflicting a significant number of reproductive age women and
without a known cause. Our laboratory has focused on understanding how miRNAs impact pro-inflammatory
and pro-fibrotic pathways in leiomyoma, and identified two miRNAsmiR-200c and miR-29c which primarily
target cell cycle, inflammation and extracellular matrix (ECM) component genes respectively as key in the
development of leiomyoma. Our recent findings using next generation sequencing has demonstrated a whole
host of non-coding RNAs including long non-coding RNAs (lncRNAs) are dysregulated in fibroids. LncRNAs
can act as sponge for miRNAs and therefore may be a driver of gene dysregulation in leiomyomas. Based on
the level of expression and functional association with tumorigenesis and tissue fibrosis we selected a group of
lncRNAs to further characterize. Using QRT-PCR we detected marked overexpression of XIST and MIAT in
leiomyomas. The sequences of these lncRNAs and preliminary data suggest they can act as miRNA sponges
for miR-29c and miR-200c. Therefore, based on our published and preliminary data we hypothesize that
leiomyoma as compared to myometrium display an altered expression of a number of lncRNAs that are
transcriptionally regulated and independently or through miRNA-guided mechanisms regulate the
expression of specific target genes functionally associated with cell cycle progression, inflammation,
fibrosis and epigenetic modification all of which are central to leiomyoma pathogenesis. To test our
core hypothesis we propose 3 specific aims. In Aim 1 we will build on our preliminary RNA sequencing study
and provide a comprehensive profile of lncRNAs, miRNAs, with concurrent mRNAs expression in large sets of
paired leiomyoma and myometrium from different race/ethnic groups derived from proliferative and secretory
phase of the menstrual cycle. Through bioinformatic analysis we will identify lncRNAs subtypes, their
chromosomal locations at loci often rearranged in leiomyoma and identify lncRNAs which could potentially act
as miRNA sponges, or competing endogenous RNAs (ceRNAs). We will also determine if presence of MED12
mutations has any impact on the profiles of these ncRNAs. Aim 2 will address the regulation and function of
MIAT and XIST in leiomyoma. Using RNA immunoprecipitation studies we will determine if these lncRNAs will
interact with miR-29c and miR-200c known to be important in fibrogenesis. At the cellular level we will assess
the role of ovarian steroids on their expression and through knockdown and knock-in strategies identify their
effects on expression of ECM and cell cycle genes. To establish the clinical relevance and therapeutic potential
of lncRNAs in Aim 3 we will determine the effect of altering the expression of XIST and MIAT which are highly
overexpressed in fibroids on fibroid progression and/or establishment in a leiomyoma animal model. This
translational proposal addresses a significant gap in knowled...

## Key facts

- **NIH application ID:** 10053201
- **Project number:** 1R01HD100529-01A1
- **Recipient organization:** LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
- **Principal Investigator:** OMID A. KHORRAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $406,478
- **Award type:** 1
- **Project period:** 2020-09-08 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053201

## Citation

> US National Institutes of Health, RePORTER application 10053201, Mechanism of Long Non-coding RNAs Action in leiomyoma (1R01HD100529-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10053201. Licensed CC0.

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