1. Elevated serum miR‐3129‐5p contributes to the progression of coronary heart disease via targeting mTOR
- Author
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Ting Zhao, Feng Gao, Zhen‐Yu Wang, and Jing Zhou
- Subjects
Oncology ,Male ,medicine.medical_specialty ,autophagy ,Microarray ,Cell ,Coronary Disease ,Severity of Illness Index ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,Internal medicine ,microRNA ,Medicine ,Gene silencing ,Animals ,Humans ,Myocytes, Cardiac ,Phosphorylation ,coronary heart disease ,PI3K/AKT/mTOR pathway ,Aged ,lcsh:R5-920 ,medicine.diagnostic_test ,business.industry ,Ribosomal Protein S6 Kinases ,TOR Serine-Threonine Kinases ,Autophagy ,Coronary Stenosis ,General Medicine ,Middle Aged ,Rats ,Gene expression profiling ,MicroRNAs ,medicine.anatomical_structure ,Gene Expression Regulation ,ROC Curve ,030220 oncology & carcinogenesis ,Case-Control Studies ,mTOR ,030211 gastroenterology & hepatology ,Beclin-1 ,Female ,business ,lcsh:Medicine (General) ,Microtubule-Associated Proteins ,miR‐3129‐5p ,Signal Transduction - Abstract
The current study aims to explore the miRNA changes that occur in the serum of patients with coronary heart disease (CHD) and healthy controls using a microarray technique, thereby exploring the potential biomarkers in the diagnosis of CHD and the underlying mechanism. Clinical data were reviewed, and venous blood samples were collected from 66 cases of CHD and 58 cases of healthy controls. MicroRNA‐wide expression profiling identified 16 miRNAs that were aberrantly decreased by ~2‐fold in the serum of patients with CHD compared to that of healthy controls. RT‐PCR analysis indicated that the expression of miR‐3129‐5p was increased the most in patients with CHD compared with that of controls. Moreover, serum miR‐3129‐5p was found to be highest in the severe stenosis group, followed by the moderate stenosis group and mild stenosis group. ROC analysis showed that serum miR‐3129‐5p could differentiate patients with CHD from controls. Further study showed that mTOR was a target gene of miR‐3129‐5p. Western blot assays demonstrated that miR‐3129‐5p significantly suppressed the phosphorylation of S6 but increased LC3II/LC3I and Beclin1 levels. Consistently, GFP‐LC3 and TEM assays indicated that miR‐3129 increased autophagy puncta in H9C2 cells. More importantly, silencing mTOR significantly decreased the expression of p‐S6 but increased LC3II/LC3I and Beclin expression even in H9C2 cells transfected with miR‐3129‐5p inhibitor, indicating that miR‐3129‐5p‐induced cell autophagy was mediated via mTOR in H9C2 cells. In summary, elevated serum miR‐3129‐5p contributes to CHD by targeting mTOR signaling and may be a therapeutic target in the treatment of CHD.
- Published
- 2021