Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State

Ischemic cardiomyopathy (ICM) is associated with abnormal microRNA expression levels that involve an altered gene profile. However, little known about the underlying causes of disruption in ICM and whether maturation compromised. Therefore, we focused on defects analysis implication biogenesis pathway redox-sensitive microRNAs (redoximiRs). Transcriptomic changes were investigated via ncRNA-seq (ICM, n = 22; controls, 8) mRNA-seq 13; control, 10). The effect hypoxia was evaluated AC16 cell line. patients showed a reduction compared to control (4.30 ± 0.94 au vs. 5.34 1.07 au, p ˂ 0.05), accompanied by deregulation pathway: decrease pre-microRNA export (XPO5, FC −1.38, 0.05) cytoplasmic processing (DICER, −1.32, 0.01). Both processes regulated cells −1.65; DICER1, −1.55; 0.01; Exportin-5, −1.81; Dicer, −1.15; 0.05). Patients displayed several redoximiRs, highlighting miR-122-5p (FC −2.41, 0.001), which maintained good correlation ejection fraction (r 0.681, We evidenced mainly linked XPO5-mediated DICER1-mediated processing, together general through redoximiRs.