The role of miR‐128 and MDFI in cardiac hypertrophy and heart failure: Mechanistic

• Published in: Journal of cellular and molecular medicine Vol. 28; no. 14; pp. e18546 - n/a
• Main Authors: Yanjun, Sun, Yunfen, Gu, Haoyi, Yao, Zhe, Wang, Jiapei, Qiu
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.07.2024; John Wiley and Sons Inc
• Subjects: Adenoviruses; Animals; Apoptosis; Apoptosis - genetics; beta Catenin - genetics; beta Catenin - metabolism; Biotechnology; Cardiac function; cardiac hypertrophy; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cardiomyocytes; Cell proliferation; Cell Proliferation - genetics; Cells; Congestive heart failure; Echocardiography; Fibrosis; Flow cytometry; Gene expression; Gene Expression Regulation; Heart failure; Heart Failure - genetics; Heart Failure - metabolism; Heart Failure - pathology; heart injury; Humans; Hypertrophy; Immunohistochemistry; Male; MDFI; Mice; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐128‐3p; Musculoskeletal system; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; MyoD; MyoD protein; Original; proliferation; Proteins; Wnt protein; Wnt Signaling Pathway - genetics; Wnt/β‐catenin pathway; Wnt1 Protein - genetics; Wnt1 Protein - metabolism; β-Catenin; China; cardiomyocytes; miR‐128‐3p; proliferation; MyoD; apoptosis; cardiac hypertrophy; MDFI; Wnt/β‐catenin pathway; heart injury
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.18546

Heart failure (HF) prognosis depends on various regulatory factors; microRNA‐128 (miR‐128) is identified as a regulator of cardiac fibrosis, contributing to HF. MyoD family inhibitor (MDFI), which is reported to be related with Wnt/β‐catenin pathway, is supposed to be regulated by miR‐128. This study investigates the interaction between miR‐128 and MDFI in cardiomyocyte development and elucidates its role in heart injury. Gene expression profiling assessed miR‐128's effect on MDFI expression in HF using qPCR and Western blot analysis. Luciferase assays studied the direct interaction between miR‐128 and MDFI. MTT, transwell, and immunohistochemistry evaluated the effects of miR‐128 and MDFI on myocardial cells in mice HF. Genescan and luciferase assays validated the interaction between miR‐128 and MDFI sequences. miR‐128 mimics significantly reduced MDFI expression at mRNA and protein levels with decrease rate of 55%. Overexpression of miR‐128 promoted apoptosis with the increase rate 65% and attenuated cardiomyocyte proliferation, while MDFI upregulation significantly enhanced proliferation. Elevated miR‐128 levels upregulated Wnt1 and β‐catenin expression, whereas increased MDFI levels inhibited these expressions. Histological analysis with haematoxylin and eosin staining revealed that miR‐128 absorption reduced MDFI expression, hindering cell proliferation and cardiac repair, with echocardiography showing corresponding improvements in cardiac function. Our findings suggest miR‐128 interacts with MDFI, playing a crucial role in HF management by modulating the Wnt1/β‐catenin pathway. Suppression of miR‐128 could promote cardiomyocyte proliferation, highlighting the potential value of the miR‐128/MDFI interplay in HF treatment.