The main adverse effect of tyrosine kinase inhibitors, such as sunitinib, is cardiac contractile dysfunction; however, the molecular mechanisms of this effect remain largely obscure. MicroRNAs (miRNAs) are key regulatory factors in both cardiovascular diseases and the tyrosine kinase pathway. Therefore, we analyzed the differential expression of miRNAs in the myocardium in mice after exposure to sunitinib using miRNA microarray. A significant downregulation of miR-146a was observed in the myocardium of sunitinib-treated mice, along with a 20% decrease in left ventricle ejection fraction (LVEF). The downregulation of miR-146a was further validated by RT-qPCR. Among the potential targets of miR-146a, we focused on and , which are closely related to cardiac contractile dysfunction. Results of luciferase reporter assay confirmed that miR-146a directly targeted the 3' untranslated region of and . Significant upregulation of PLN and ANK2 at the mRNA and protein levels was observed in the myocardium of sunitinib-treated mice. Cardiac-specific overexpression of miR-146a prevented the deteriorate effect of SNT on calcium transients, thereby alleviating the decreased contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). SiRNA knockdown of PLN or ANK2 prevented sunitinib-induced suppression of contractility in hiPSC-CMs. Therefore, our and results showed that sunitinib downregulated miR-146a, which contributes to cardiac contractile dysfunction by regulating the downstream targets PLN and ANK2, and that upregulation of miR-146a alleviated the inhibitory effect of SNT on cardiac contractility. Thus, miR-146a could be a useful protective agent against sunitinib-induced cardiac dysfunction.
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http://dx.doi.org/10.3389/fphar.2019.00914 | DOI Listing |
Curr Pharm Des
January 2025
Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
Introduction: Sepsis, like neutropenic sepsis, is a medical condition in which our body overreacts to infectious agents. It is associated with damage to normal tissues and organs by the immune system, which leads to the spread of inflammation throughout our body. Of note, microRNAs (miRNAs) have been found to have a critical role in the sepsis progression.
View Article and Find Full Text PDFIndian J Ophthalmol
December 2024
Department of Biochemistry, Trakya University School of Pharmacy, Edirne, Turkey.
Introduction: This study aimed to investigate alterations in intravitreal microRNA and vascular endothelial growth factor (VEGF) levels in patients with proliferative diabetic retinopathy (PDR) as these factors are implicated in PDR pathogenesis.
Methods: Fifty-two participants, including 26 patients with PDR and 26 controls without diabetes, were included in this study. VEGF levels were assessed using ELISA, and seven microRNAs (miRNAs) (miR-19a, miR-20b, miR-27a, miR-124, miR-126-3p, miR-146a, and miR-200b) were analyzed using quantitative real-time PCR.
J Appl Genet
December 2024
Department of Molecular Neurooncology, Institute of Bioorganic Chemistry Polish Academy of Sciences, Zygmunta Noskowskiego 12/14, 61-704, Poznan, Poland.
To find a distinct non-coding RNA characteristic for idiopathic uveitis in the pediatric population. To explore the autoimmune-related miRNA expression profile in pediatric patients with idiopathic uveitis (IU) and juvenile idiopathic arthritis-associated uveitis (JIA-AU) and find a common molecular background for idiopathic uveitis and other autoimmune diseases. The expression levels of miRNAs were analyzed by quantitative real-time PCR using serum samples from patients with idiopathic uveitis (n = 8), juvenile idiopathic arthritis-associated uveitis (n = 7), and healthy controls.
View Article and Find Full Text PDFFront Med (Lausanne)
December 2024
Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czechia.
In Vitro Cell Dev Biol Anim
December 2024
Department of Neurology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, 570208, China.
MicroRNA-146a-5p (miR-146a-5p) actively participates in the process of cerebral ischemia-reperfusion (CI/R) injury. Dysregulation of the tumor necrosis factor receptor-associated factor 6 (TRAF6)/nuclear factor kappa-B (NF-κB) p65 axis is closely associated with inflammatory response. This study aimed to investigate the potential involvement of miR-146a-5p and TRAF6/NF-κB p65 in mediating CI/R progression in vitro.
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