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Updated: Nov 1, 2025
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Published on: June 15, 2018
Long non-coding RNA THRIL is upregulated in coronary heart disease and binds to microRNA-424 to upregulate TXNIP in
1Department of Internal Medicine, the Fourth Hospital of Zaozhuang City, Zaozhuang 277000, Shandong, PR China.
Insights
Inhibiting the long non-coding RNA THRIL protects against heart injury in mice with coronary heart disease (CHD). This occurs by regulating the miR-424/TXNIP/p53 pathway, offering a potential therapeutic target for CHD.
Area of Science:
- Molecular Biology
- Cardiology
- Genetics
Background:
- Cardiovascular diseases, especially coronary heart disease (CHD), are leading causes of mortality.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their role in myocardial injury.
- THRIL has emerged as a key lncRNA implicated in cardiovascular pathophysiology.
Purpose of the Study:
- To investigate the regulatory role of the lncRNA THRIL in myocardial injury associated with CHD in a mouse model.
- To elucidate the molecular mechanism by which THRIL influences CHD-induced cardiac damage.
- To explore the potential of THRIL inhibition as a therapeutic strategy for CHD.
Main Methods:
- Establishment of a mouse model of CHD using a high-fat diet.
- lncRNA microarray analysis and RT-qPCR for differential expression of lncRNAs.
- Silencing of THRIL using small interfering RNA (si-THRIL) and assessment of cardiac function and biomarkers.
- Bioinformatics prediction, dual-luciferase assays, and subcellular fractionation to determine molecular interactions.
- Investigation of the miR-424/TXNIP/p53 signaling axis.
Main Results:
- Silencing THRIL in CHD mice significantly attenuated myocardial damage, improving left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), and restoring HDL-C levels.
- THRIL inhibition led to decreased levels of cardiac injury markers (HMI, LVMI, TC, TG, LDL-C, CK-MB, cTnI).
- Mechanistic studies revealed that THRIL directly binds to microRNA-424 (miR-424), inhibiting its interaction with TXNIP and consequently promoting TXNIP expression.
- The cardioprotective effects of THRIL silencing were diminished with miR-424 downregulation, and TXNIP was found to mediate myocardial injury via the p53 pathway.
Conclusions:
- THRIL inhibition demonstrates significant cardioprotective effects in a mouse model of CHD.
- The study identifies a novel regulatory pathway involving THRIL, miR-424, TXNIP, and p53 in the context of myocardial injury.
- Targeting the THRIL/miR-424/TXNIP/p53 axis represents a promising therapeutic avenue for managing CHD-related myocardial damage.
Abstract:
Cardiovascular disease, particularly coronary heart disease (CHD), is one of the diseases with the highest fatality. The close correlation between long non-coding RNAs (lncRNAs) and the occurrence and development of myocardial injury has been highlighted recently. This article mainly focused on the regulation of THRIL on myocardial injury caused by CHD in mice. After establishment of a mouse model with CHD, a lncRNA microarray analysis was performed on mouse myocardial tissues to detect differentially expressed lncRNAs, followed by RT-qPCR validation. CHD was induced in mice by high-fat diet feeding and THRIL was silenced using si-THRIL. The results showed that treating CHD mice with si-THRIL attenuated myocardial damage by restoring LVEF, LVFS, and HDL-C levels, while lowering HMI, LVMI, TC, TG, LDL-C, CK-MB, and cTnI levels. Meanwhile, mechanistical studies using bioinformatics prediction, dual-luciferase and subcellular fractionation assays revealed that THRIL bound to microRNA (miR)-424, inhibited miR-424 interaction with TXNIP and promoted TXNIP expression in the myocardial tissues. The cardioprotective effects of si-THRIL on mice were attenuated when miR-424 was downregulated. Moreover, TXNIP exerted its effects on myocardial injury by mediating the p53 pathway. Taken together, this study demonstrated that THRIL inhibition alleviates myocardial injury in CHD possibly through the miR-424/TXNIP/p53 axis.
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