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Updated: Jun 11, 2025

In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
Hsa-circ-ACSL1 Enhances Apoptosis and Autophagy in Myocarditis Cardiomyocytes Through the miR-7-5p/XBP1 Axis
Fu Li Liang1, You Fu Tong1, Xiao Chun Zhang1
1Department of Coronary Heart Disease II, Qinghai Cardio-Cerebrovascular Specialty Hospital, Qinghai High Altitude Medical Research Institute, Xining City, Qinghai Province, China.
Insights
Circular RNA ACSL1 (circ-ACSL1) exacerbates viral myocarditis (VMC) by increasing X-box binding protein 1 (XBP1) expression via microRNA-7-5p (miR-7-5p). circ-ACSL1 may serve as a diagnostic biomarker and therapeutic target for VMC.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- RNA Biology
Background:
- Viral myocarditis (VMC) is a significant cardiovascular disease.
- Circular RNAs (circRNAs) are implicated in cardiovascular disease pathophysiology.
- The role of circRNAs in VMC is not well understood.
Purpose of the Study:
- To investigate the biological functions of circ-ACSL1 in VMC.
- To elucidate the regulatory mechanisms of circ-ACSL1 in VMC.
Main Methods:
- VMC models were established using coxsackievirus B3 (CVB3) in mice and cell lines.
- Inflammation, myocardial injury, apoptosis, and autophagy were assessed.
- Expression levels of circ-ACSL1, microRNA-7-5p (miR-7-5p), and X-box binding protein 1 (XBP1) were manipulated.
Main Results:
- Reducing circ-ACSL1 inhibited inflammation, autophagy, and apoptosis in VMC.
- circ-ACSL1 targets miR-7-5p, regulating downstream XBP1.
- Depleting miR-7-5p reversed the effects of circ-ACSL1 depletion.
- Overexpressing circ-ACSL1 worsened VMC, an effect rescued by XBP1 knockdown.
Conclusions:
- circ-ACSL1 promotes VMC by upregulating XBP1 through sponging miR-7-5p, leading to myocardial inflammation.
- circ-ACSL1 shows potential as a biomarker for VMC diagnosis and a therapeutic target.
Background:
Viral myocarditis (VMC) is a common cardiovascular disease, and circular RNAs (circRNAs) have been identified to play an important role in the pathophysiology of cardiovascular disease. However, the clinical significance, biological functions, and regulatory mechanisms of circRNAs in VMC remain poorly understood. Therefore, this study explored the biological functions and regulatory mechanisms of circ-ACSL1 in VMC.
Methods:
The animal and cell models of VMC were established by infecting BABL/C mice and interleukin-2 cells with coxsackievirus B3 (CVB3). Pro-inflammatory factors, markers of myocardial injury, apoptosis, and autophagy were detected to evaluate the degree of myocardial inflammation and myocardial injury after altering circ-ACSL1, microRNA-7-5p (miR-7-5p), and X-box binding protein 1 (XBP1) expression alone or in combination.
Results:
Knocking down circ-ACSL1 could inhibit inflammation, autophagy, and apoptosis in VMC animals and cells. Mechanistically, circ-ACSL1 targeted miR-7-5p to regulate the downstream target XBP1. In addition, depleting miR-7-5p rescued the therapeutic effect of depleting circ-ACSL1. Overexpression of circ-ACSL1 aggravated VMC; however, this effect was saved by knocking down XBP1.
Conclusion:
By competitively absorbing miR-7-5p, circ-ACSL1 increases XBP1 expression and aggravates myocardial inflammation. Meaningfully, VMC treatment may benefit from circ-ACSL1 as a potential biomarker for precise diagnosis and as a potential therapeutic target.
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