» Articles » PMID: 33817315

Knockdown of TUG1 Rescues Cardiomyocyte Hypertrophy Through Targeting the MiR-497/MEF2C Axis

Overview
Journal Open Life Sci
Specialty Biology
Date 2021 Apr 5
PMID 33817315
Citations 4
Authors
Affiliations
Soon will be listed here.
Abstract

The aim of this study was to investigate the detailed role and molecular mechanism of long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in cardiac hypertrophy. Cardiac hypertrophy was established by transverse abdominal aortic constriction (TAC) or angiotensin II (Ang II) treatment . Levels of lncRNA TUG1, miR-497 and myocyte enhancer factor 2C (MEF2C) mRNA were assessed by quantitative reverse transcriptase PCR (qRT-PCR). Western blot assay was performed to determine the expression of MEF2C protein. The endogenous interactions among TUG1, miR-497 and MEF2C were confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Our data indicated that TUG1 was upregulated and miR-497 was downregulated in the TAC rat model and Ang II-induced cardiomyocytes. TUG1 knockdown or miR-497 overexpression alleviated the hypertrophy induced by Ang II in cardiomyocytes. Moreover, TUG1 acted as a sponge of miR-497, and MEF2C was directly targeted and repressed by miR-497. miR-497 overexpression mediated the protective role of TUG1 knockdown in Ang II-induced cardiomyocyte hypertrophy. MEF2C was a functional target of miR-497 in regulating Ang II-induced cardiomyocyte hypertrophy. In addition, TUG1 regulated MEF2C expression through sponging miR-497. Knockdown of TUG1 rescued Ang II-induced hypertrophy in cardiomyocytes at least partly through targeting the miR-497/MEF2C axis, highlighting a novel promising therapeutic target for cardiac hypertrophy treatment.

Citing Articles

Posttranscriptional Regulation by Proteins and Noncoding RNAs.

Aranega A, Franco D Adv Exp Med Biol. 2024; 1441:313-339.

PMID: 38884719 DOI: 10.1007/978-3-031-44087-8_17.


Non-coding RNAs in the pathophysiology of heart failure with preserved ejection fraction.

Jalink E, Schonk A, Boon R, Juni R Front Cardiovasc Med. 2024; 10:1300375.

PMID: 38259314 PMC: 10800550. DOI: 10.3389/fcvm.2023.1300375.


Overexpressing lnc240 Rescues Learning and Memory Dysfunction in Hepatic Encephalopathy Through miR-1264-5p/MEF2C Axis.

Zhang H, Yu G, Li J, Tu C, Hui Y, Liu D Mol Neurobiol. 2023; 60(4):2277-2294.

PMID: 36645630 DOI: 10.1007/s12035-023-03205-1.


Interactions between the ERK1/2 signaling pathway and PCAF play a key role in PE‑induced cardiomyocyte hypertrophy.

Mao Q, Wu S, Peng C, Peng B, Luo X, Huang L Mol Med Rep. 2021; 24(3).

PMID: 34278478 PMC: 8281443. DOI: 10.3892/mmr.2021.12275.

References
1.
Pereira A, Clemente C, Cardoso A, Theizen T, Rocco S, Judice C . MEF2C silencing attenuates load-induced left ventricular hypertrophy by modulating mTOR/S6K pathway in mice. PLoS One. 2009; 4(12):e8472. PMC: 2794538. DOI: 10.1371/journal.pone.0008472. View

2.
Wang Z, Zhang X, Ji Y, Zhang P, Deng K, Gong J . The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy. Nat Med. 2016; 22(10):1131-1139. PMC: 5053883. DOI: 10.1038/nm.4179. View

3.
Bernardo B, Weeks K, Pretorius L, McMullen J . Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies. Pharmacol Ther. 2010; 128(1):191-227. DOI: 10.1016/j.pharmthera.2010.04.005. View

4.
Rohini A, Agrawal N, Koyani C, Singh R . Molecular targets and regulators of cardiac hypertrophy. Pharmacol Res. 2009; 61(4):269-80. DOI: 10.1016/j.phrs.2009.11.012. View

5.
Xiao L, Gu Y, Sun Y, Chen J, Wang X, Zhang Y . The long noncoding RNA XIST regulates cardiac hypertrophy by targeting miR-101. J Cell Physiol. 2019; 234(8):13680-13692. DOI: 10.1002/jcp.28047. View