A930024E05Rik is a hypoxia-upregulated lncRNA that facilitates atrial fibrosis by sponging let-7 miRNAs to modulate collagen expression in cardiomyocytes

Hypoxia-induced atrial fibrosis plays a central role in the development and progression of atrial fibrillation (AF), yet the involvement of long noncoding RNAs (lncRNAs) in this process is not fully defined. This study aimed to identify hypoxia-responsive lncRNAs and investigate their functional roles in hypoxia-mediated fibrotic remodeling. Transcriptomic profiling of HL-1 atrial cardiomyocytes under hypoxic conditions, followed by bioinformatic prediction and molecular validation, including luciferase reporter assays, RNA pull-down, RNA immunoprecipitation, and gain- and loss-of-function analyses, were performed to delineate the downstream effects. Among lncRNA candidates, A930024E05Rik was markedly upregulated by hypoxia and inversely associated with let-7 miRNA expression. Further analyses demonstrated that A930024E05Rik physically interacts with let-7a and let-7e, is enriched in let-7-dependent gene-silencing machinery, and modulates the expression of collagen genes, COL1A1 and COL3A1. Functional assessments demonstrated that A930024E05Rik enhances collagen production by alleviating let-7-mediated repression, as evidenced by reciprocal effects of gene silencing and overexpression. In conclusion, these findings support a competing endogenous RNA mechanism in which A930024E05Rik modulates let-7 miRNA availability to control collagen expression in hypoxic cardiomyocytes, highlighting potential avenues for the application of this A930024E05Rik-let-7 regulatory axis on AF management.