Identification of miRNA Targeting Genes Involved in Hyperlipidemia as a Therapeutic Strategy for Cardiovascular Diseases

Abstract

Hyperlipidemia is a common metabolic disorder and one of the independent risk factors for the onset of cardiovascular diseases (CVDs). CVDs are the leading cause of mortality in diabetic patients globally. In recent years, compelling evidence suggested that aberrant miRNA expression has been implicated in the pathophysiology of many diseases and is considered a prognostic biomarker for early diagnosis of heart diseases. Therefore, analysis of hyperlipidemia-related miRNAs is a potential approach to selectively inhibit or activate specific genes for therapeutic purposes. We identified and screened a set of hyperlipidemia and CVDs associated genes by the genetic testing registry (GTR) of NCBI. Furthermore, we predicted highly conserved putative miRNAs that target genes through binding at 8mer units by using bioinformatics repositories Targetscan, miRBase, and miRanda. Insilico miRNAs profiling of shortlisted genes revealed the target miRNAs; ACTN4 (miR-153-3p), ADCY3 (miR-3681-3p/ 216a-3p/ 128-3p/ 873-5p.1/ 92b-3p), LEP (miR-532-5p/ 29b-3p/ 29a-3p/ 29c-3p/ 125b-5p/ 125a-5p. GHR (miR-151a-3p/ 19a-3p/ 19b-3p/ 143-3p/15b-5p/ 15a-5p/ 195-5p), LPL(miR-27a-3p/ 27b-3p/ 29b-3p/, 29a-3p/ 29c-3p) LRP6 (miR-183-5p.1/ 124-3p.2/ 506-3p/ 3681-3p/ 128-3p/ 216a-3p/ 27a-3p/ 27b-3p/ 543/ 140-3p.1PCSK9 (miR-202-5p/155-5p), USF1 (miR-338-3p/ 296-5p), TNFRSF1B (miR-7/4458miR-4500), HMCN1(miR-29c-3p/ 29b-3p/ 29a-3p/ 199a-5p/ 199b-5p), KDM3A(miR-140-3p.1/ 30a-5p/ 30d-5p/ 30c-5p/ 30b-5p/ 30e-5p/ 542-3p), SEC61A1(miR-218-5p/ 331-3p), ADD1(miR-27b-3p/ 27a-3p/ 299-3p/ 448), PPARGC1B(miR-30e-5p/ 30a-5p/ 30d-5p/ 30c-5p/ 30b-5p/ 449b-5p/ 449a/ 34c-5p/ 30/ 27a-3p/ 27b-3p/ SH2B1(miR-142-3p.1/ 136-5p), PPARA (miR-19a-3p/ 19b-3p/ 9-5p/ 101-3p.2/ 4262/ 181c-5p/ 181d-5p/ 181b-5p/ 181a-5p/ 506-3p/ 124-3p.2). Conclusively, our predicted microRNAs may provide better insights towards miRNA-based treatment strategies against CVDs.