Role of MicroRNA-29 and ADAM12 in the Regulation of REST Dependent Signaling Pathways in Uterine Fibroids
type: CreativeWork
description: Uterine fibroids, also known as leiomyomas, are benign smooth muscle cell (SMC) tumors of the myometrium and are the most frequent reason for a hysterectomy. Although benign, these tumors pose a significant burden on patients with symptoms of abdominal pain, pressure, uterine bleeding, and infertility; creating a great liability for the US economy with an annual estimated cost of up to $34 billion. Currently there are no long-term treatments for fibroids that will leave fertility intact, mainly because the mechanism of pathogenesis of these tumors is largely unknown. One of the key characteristics of uterine fibroids is the excessive deposition and reorganization of extracellular matrix (ECM). Altered ECM, which amplifies growth factor signaling and disrupts mechanosensing, has been proposed to promote fibroid tumor growth. Analysis of available gene expression datasets from GEO database indicates that ADAM12 expression is dramatically upregulated in fibroids. As a member of the A-Disintegrin And Metalloprotease family of matrix modifying enzymes, ADAM12 is known to cleave ECM proteins, activate epidermal growth factor (EGF) and Insulin-like growth factor (IGF) signaling and promote tumorigenesis. Our lab has recently shown the expression of RE1 suppressing transcription factor /neuron-restrictive silencing factor (REST/NRSF), a known tumor suppressor, to be lost in fibroids. Upon further analysis, we found silencing REST in primary myometrial SMCs led to an increase in a number of downstream target genes, a profile similar to what is seen in fibroid tumor samples. Furthermore, Ingenuity® pathway analyses of gene expression datasets for fibroids indicate that the loss of REST and the increase in ADAM12 expression in leiomyomas could be linked through microRNA-29 (miR-29). In addition, in cultured mammary tumor cell lines, miR-29 is known to directly regulate ADAM12 expression. Compared to normal myometrium, uterine fibroids express significantly lower levels of miR-…
abstract: Uterine fibroids, also known as leiomyomas, are benign smooth muscle cell (SMC) tumors of the myometrium and are the most frequent reason for a hysterectomy. Although benign, these tumors pose a significant burden on patients with symptoms of abdominal pain, pressure, uterine bleeding, and infertility; creating a great liability for the US economy with an annual estimated cost of up to $34 billion. Currently there are no long-term treatments for fibroids that will leave fertility intact, mainly because the mechanism of pathogenesis of these tumors is largely unknown. One of the key characteristics of uterine fibroids is the excessive deposition and reorganization of extracellular matrix (ECM). Altered ECM, which amplifies growth factor signaling and disrupts mechanosensing, has been proposed to promote fibroid tumor growth. Analysis of available gene expression datasets from GEO database indicates that ADAM12 expression is dramatically upregulated in fibroids. As a member of the A-Disintegrin And Metalloprotease family of matrix modifying enzymes, ADAM12 is known to cleave ECM proteins, activate epidermal growth factor (EGF) and Insulin-like growth factor (IGF) signaling and promote tumorigenesis. Our lab has recently shown the expression of RE1 suppressing transcription factor /neuron-restrictive silencing factor (REST/NRSF), a known tumor suppressor, to be lost in fibroids. Upon further analysis, we found silencing REST in primary myometrial SMCs led to an increase in a number of downstream target genes, a profile similar to what is seen in fibroid tumor samples. Furthermore, Ingenuity® pathway analyses of gene expression datasets for fibroids indicate that the loss of REST and the increase in ADAM12 expression in leiomyomas could be linked through microRNA-29 (miR-29). In addition, in cultured mammary tumor cell lines, miR-29 is known to directly regulate ADAM12 expression. Compared to normal myometrium, uterine fibroids express significantly lower levels of miR-…
author: Farahbakhsh, Mina
language: en
keywords: Physiology, ADAM12, Leiomyoma, MicroRNA-29, Notch, REST, Uterine Fibroids
date published: 2017-05-31
date modified: 2026-07-24T02:44:44Z
provider: University of Kansas
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Kansas

PropertyValue
property ID: Handle
value: http://hdl.handle.net/1808/26945