| First Author | Qin XD | Year | 2019 |
| Journal | Eur Rev Med Pharmacol Sci | Volume | 23 |
| Issue | 13 | Pages | 5941-5948 |
| PubMed ID | 31298345 | Mgi Jnum | J:296532 |
| Mgi Id | MGI:6467907 | Doi | 10.26355/eurrev_201907_18340 |
| Citation | Qin XD, et al. (2019) Loss of microRNA-27a induces cardiac dysfunction through activating FoxO1. Eur Rev Med Pharmacol Sci 23(13):5941-5948 |
| abstractText | OBJECTIVE: To elucidate how microRNA-27a and FoxO1 regulate cardiac dysfunction in mice. MATERIALS AND METHODS: Expression levels of ANP, BNP, beta-MHC, alpha-SMA, Fn1, and Periostin in myocardial tissues of 2-month-old and 8-month-old microRNA-27a-KO mice and age-matched wild-type mice were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Dual-luciferase reporter gene assay was conducted in H9C2 cells to verify the binding condition between microRNA-27a and FoxO1. By transfection of microRNA-27a mimics or inhibitor, FoxO1 expression in H9C2 cells was determined at the mRNA and protein levels. HW/BW [ratio of heart weight (mg) and body weight (mg)], HW/TL [ratio of heart weight (mg) and tibial length (mm)], LVPWDT [left ventricular posterior wall diastolic thickness (mm)], LVEDD [left ventricular end-diastolic dimension (mm)], and FS (fractional shortening) in mice treated with or without FoxO1 inhibitor AS1842856 were accessed through echocardiography. RESULTS: MicroRNA-27a-KO mice had larger LVEDD, HW/BW, and HW/TL, but lower FS and LVPWDT than those of age-matched wild-type mice. Besides, higher levels of ANP, BNP, beta-MHC, alpha-SMA, Fn1, and Periostin were observed in myocardial tissues of microRNA-27a-KO mice compared with those of age-matched wild-type mice. Dual-luciferase reporter gene assay revealed lower luciferase activity in H9C2 cells co-transfected with microRNA-27a mimics and wild-type FoxO1 than that of controls. The expression level of FoxO1 was negatively regulated by microRNA-27a in H9C2 cells at the mRNA and protein levels. After AS1842856 injection, HW/BW, HW/TL, and LVEDD in microRNA-27a-KO mice markedly decreased, whereas FS and LVPWDT elevated. By comparison, AS1842856 injection did not influence cardiac development in wild-type mice. CONCLUSIONS: MicroRNA-27a knockout could induce cardiac dysfunction in mice through upregulating FoxO1 expression. |
