miR-30e-5p Mitigates Hypoxia-Induced Apoptosis in Human Stem Cell-Derived Cardiomyocytes by Suppressing Bim

Abstract

Coronary microembolization can cause slow or no reflow, which is one of the crucial reasons for reverse of clinical advantage from cardiac reperfusion therapy. miRNAs and apoptosis are dramatically involved in the occurrence and process of cardiovascular diseases. Fortunately, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as an appealing model for the evaluation of cardiovascular diseases. Therefore, our study was designed to explore the role of miR-30e-5p and apoptosis in a hypoxia-induced hiPSC-CM injury model. Our results showed that the expression levels of miR-30e-5p were overtly downregulated in a time-dependent manner under hypoxic conditions. Expression of miR-30e-5p was significantly downregulated after 24 hours of hypoxia, hypoxia treatment dramatically induced apoptosis. Calcium handling capability significantly decreased after 24 hours of hypoxia treatment. miR-30e-5p overexpression partially mitigated hypoxia-induced apoptosis and rescued hypoxia-induced calcium handling defects in hiPSC-CMs. The luciferase reporter assay showed that miR-30e-5p can directly target the 3'-UTR of Bim, which is an apoptosis activator and autophagy suppressor. The mRNA and protein of Bim remarkably increased after hypoxia treatment and reduced with miR-30e-5p overexpression. Moreover, downregulation of Bim mitigated hypoxia-induced apoptosis and activated autophagy. These results demonstrated that miR-30e-5p mitigated hypoxia-induced apoptosis in hiPSC-CMs at least in part via Bim suppression and subsequent autophagy activation. Our study suggested miR-30e-5p may act as a potential therapeutic target for coronary microembolization.

miR‐30e‐5p represses angiogenesis and metastasis by directly targeting AEG‐1 in squamous cell carcinoma of the head and neck

“…Based on review of the literature (present study), miR‐30e‐5p modulates diverse mRNA targets in different disease situations, including cancer. These target genes are listed as follows: NFAT5 , TUSC3 , Bim , USP22 , MYBL2 , ITGA6 , ITGB1 , LRP6 and YAP1 . In our current study, miR‐30e‐5p was found to directly link to the 3′‐UTR domain of AEG‐1 mRNA, which accelerates the degradation of AEG‐1 mRNA and eventually reduces the level of AEG‐1 protein.…”

Beyond Family: Modeling Non-hereditary Heart Diseases With Human Pluripotent Stem Cell-Derived Cardiomyocytes

“…Indeed, several studies describe little or no response to I/R-mimetic conditions in unprimed hPSC-CMs, although showing minimal but relatively significant cardioprotection by the individual molecules of interest (Hsieh et al, 2015;Wei et al, 2017;Mo et al, 2019). Our own experiments with oxygen/glucose deprivation in microfluidic devices show clearly divergent responses of postnatal murine cardiomyocytes and unprimed hPSC-CMs characterized by abnormal intracellular glycogen stores (Martewicz et al, 2018).…”

Circulating MicroRNA-30e Predicts Left Ventricular Hypertrophy In Essential Hypertensive Patients

“…For example, miR-30e in the myocardium is inhibited after the occurrence of coronary microembolization, together with decreased cardiac function 27 . miR-30e alleviates apoptosis induced by hypoxia in human stem cell-derived cardiomyocytes 28 . Of note, the effect of miR-30e on cardiomyocyte hypertrophy was reported in a series of cellular and animal studies.…”