# Function of Long Non-Coding RNA MD1 in Leiomyoma Pathogenesis

> **NIH NIH R03** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 2022 · $77,050

## Abstract

Uterine leiomyoma (fibroids) develop during reproductive years in over 70% of women; however, their etiology
remains unknown. Our group has identified two miRNAs, miR-200c and miR-29c, which are critical to
regulation of genes functionally associated with cell cycle, cellular transformation, inflammation and
extracellular matrix accumulation and thus of great significance to fibroid pathogenesis. Our recent findings
using next generation sequencing provided a comprehensive profile of non-coding RNAs including long non-
coding RNAs (lncRNAs) as well as novel groups of small non-coding RNAs (sncRNAs). Our preliminary
findings here have identified aberrant expression of linc-MD1 and miR-135 family in fibroids and thus the
impetus for this proposal. Using qRT-PCR we detected markedly reduced levels of linc-MD1 while
significantly higher expression of miR-135 family in leiomyomas. The sequences of the linc-MD1 and our
preliminary data suggest that linc-MD1 can act as miRNA sponge for miR-135 family (miR-135a/-135b) in
leiomyoma smooth muscle cells. Therefore, based on this preliminary data we hypothesize that leiomyoma
as compared to myometrium displays reduced expression of linc-MD1 which through a miRNA-guided
mechanism involving miR-135 regulates the expression of specific target genes functionally
associated with Wnt/β-catenin signaling pathway which is known to be central to leiomyoma
pathogenesis. To test our core hypothesis we propose 2 specific aims. In Aim 1 we will determine the
interaction between linc-MD1 and miR-135 family by RNA immunoprecipitation and RNA pull-down assay. We
will over or under express linc-MD1 in LSMC or MSMC spheroid cells and determine its effect on miR-135
family and its downstream target genes namely GSK3β and APC which are known to regulate β-Catenin
degradation. In these experiments β-Catenin, its phosphorylated form and its nuclear localization will be
determined in response to overexpression and knockdown studies in vitro. To establish the clinical relevance
and therapeutic potential of linc-MD1 in Aim 2 we will determine the effect of linc-MD1 overexpression in
leiomyoma cells on fibroid progression in a leiomyoma animal model. This translational proposal addresses a
significant gap in knowledge on the role of a novel lncRNA-miRNA network in the pathogenesis of fibroids
which is a priority area of investigation for NIH, and could potentially be targeted for therapeutic purposes for
fibroids.

## Key facts

- **NIH application ID:** 10370413
- **Project number:** 5R03HD101852-02
- **Recipient organization:** LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
- **Principal Investigator:** OMID A. KHORRAM
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $77,050
- **Award type:** 5
- **Project period:** 2021-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370413

## Citation

> US National Institutes of Health, RePORTER application 10370413, Function of Long Non-Coding RNA MD1 in Leiomyoma Pathogenesis (5R03HD101852-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10370413. Licensed CC0.

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