Long Noncoding RNA MIAT Modulates the Extracellular Matrix Deposition in Leiomyomas by Sponging MiR-29 Family

Overview

Journal Endocrinology

Publisher Oxford University Press

Specialty Endocrinology

Date 2021 Sep 7

PMID 34491311

Citations 11

Authors

Tsai-Der Chuang

Derek Quintanilla

Drake Boos

Omid Khorram

Affiliations

Soon will be listed here.

Abstract

The objective of this study was to determine the expression and functional role of a long noncoding RNA (lncRNA) MIAT (myocardial infarction-associated transcript) in leiomyoma pathogenesis. Leiomyoma compared with myometrium (n = 66) expressed significantly more MIAT that was independent of race/ethnicity and menstrual cycle phase but dependent on MED12 (mediator complex subunit 12) mutation status. Leiomyomas bearing the MED12 mutation expressed higher levels of MIAT and lower levels of microRNA 29 family (miR-29a, -b, and -c) compared with MED12 wild-type leiomyomas. Using luciferase reporter activity and RNA immunoprecipitation analysis, MIAT was shown to sponge the miR-29 family. In a 3-dimensional spheroid culture system, transient transfection of MIAT siRNA in leiomyoma smooth muscle cell (LSMC) spheroids resulted in upregulation of miR-29 family and downregulation of miR-29 targets, collagen type I (COL1A1), collagen type III (COL3A1), and TGF-β3 (transforming growth factor β-3). Treatment of LSMC spheroids with TGF-β3 induced COL1A1, COL3A1, and MIAT levels, but repressed miR-29 family expression. Knockdown of MIAT in LSMC spheroids blocked the effects of TGF-β3 on the induction of COL1A1 and COL3A1 expression. Collectively, these results underscore the physiological significance of MIAT in extracellular matrix accumulation in leiomyoma.

Citing Articles

Differential Expression of Small Non-Coding RNAs in Uterine Leiomyomas.

Chuang T, Ton N, Rysling S, Baghdasarian D, Khorram O Int J Mol Sci. 2025; 26(4).

PMID: 40004152 PMC: 11854932. DOI: 10.3390/ijms26041688.

The Functional Role of the Long Non-Coding RNA LINCMD1 in Leiomyoma Pathogenesis.

Chuang T, Ton N, Rysling S, Khorram O Int J Mol Sci. 2024; 25(21).

PMID: 39519092 PMC: 11545963. DOI: 10.3390/ijms252111539.

In Vivo Effects of Bay 11-7082 on Fibroid Growth and Gene Expression: A Preclinical Study.

Chuang T, Ton N, Rysling S, Khorram O Cells. 2024; 13(13.

PMID: 38994944 PMC: 11240737. DOI: 10.3390/cells13131091.

Targeting the long non-coding RNA MIAT for the treatment of fibroids in an animal model.

Chuang T, Ton N, Manrique N, Rysling S, Khorram O Clin Sci (Lond). 2024; 138(12):699-709.

PMID: 38817011 PMC: 11166562. DOI: 10.1042/CS20240190.

The Effect of Race/Ethnicity and MED12 Mutation on the Expression of Long Non-Coding RNAs in Uterine Leiomyoma and Myometrium.

Chuang T, Ton N, Rysling S, Boos D, Khorram O Int J Mol Sci. 2024; 25(2).

PMID: 38279317 PMC: 10816284. DOI: 10.3390/ijms25021307.

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