Analysis of the snoRNA profile in ischemic and dilated cardiomyopathy

Abstract Introduction In last decade, knowledge of how non-coding RNAs (ncRNAs) contribute to the pathogenesis of cardiovascular disease has increased exponentially. However, other than miRNAs, relatively little is known about how other small RNAs specifically contribute to heart failure. snoRNAs have been known for decades, mainly for their role in biogenesis and ribosomal modification. Moreover, recent studies have provided fundamental information on how snoRNA regulated non-coding RNA expression. However, the contribution of these non-coding RNAs to human disease is a relatively new area of research, with heart failure being relatively unknown and understudied. Purpose We aimed to investigate whether snoRNA expression is regulated during heart failure from dilated (DCM) and ischemic (ICM) origin, and how its biogenesis is affected by the pathophysiology of the disease. Methods Heart tissue samples from ICM (n=22) and DCM (n=20) patients and control (CNT, n=8) subjects were analyzed by non-coding RNA-Sequencing (ncRNA-Seq) to evaluate transcriptome changes in snoRNA/scaRNA. In addition, through mRNA sequencing we analyzed the biogenesis pathway of these ncRNA in ICM (n=13) and DCM (n=13) patients compared to CNT (n=10). Microarray analysis was used to validate the alterations found in the snoRNA/scaRNA expression (ICM, n=24; DCM, n=20; CNT, n=10). Results A generalized alteration of the snoRNA biogenesis pathway was not observed, we only found NOLC1 underexpression in ICM patients (FC=-1.42, p