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

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.

• Authors: Tsai-Der Chuang, Derek Quintanilla, Drake Boos, Omid Khorram
• Journal: Endocrinology (Endocrinology) Vol. 162 Issue 11 (11 01 2021) ISSN: 1945-7170 [Electronic] United States
• PMID: 34491311 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• MIRN29a microRNA, human
• Miat long non-coding RNA
• MicroRNAs
• RNA, Long Noncoding

Topics

• Adult
• Cells, Cultured
• Down-Regulation (genetics)
• Extracellular Matrix (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Leiomyoma (genetics, metabolism, pathology)
• MicroRNAs (genetics)
• Middle Aged
• Multigene Family (genetics)
• Protein Multimerization (genetics)
• RNA, Long Noncoding (physiology)
• Uterine Neoplasms (genetics, metabolism, pathology)