Competing Endogenous RNA Regulatory Networks of hsa_circ_0126672 in Pathophysiology of Coronary Heart Disease

Author:

Rafiq Muhammad12ORCID,Dandare Abdullahi13,Javed Arham12,Liaquat Afrose2ORCID,Raja Afraz Ahmad1,Awan Hassaan Mehboob1,Khan Muhammad Jawad1ORCID,Naeem Aisha45

Affiliation:

1. Department of Biosciences, COMSATS University Islamabad, Islamabad 45550, Pakistan

2. Department of Biochemistry, Shifa College of Medicine, Shifa Tameer-e-Millat University, Islamabad 45550, Pakistan

3. Department of Biochemistry, Usmanu Danfodiyo University Sokoto, Sokoto P.M.B 2346, Nigeria

4. Health Research Governance Department, Ministry of Public Health, Doha P.O. Box 42, Qatar

5. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA

Abstract

Coronary heart disease (CHD) is a global health concern, and its molecular origin is not fully elucidated. Dysregulation of ncRNAs has been linked to many metabolic and infectious diseases. This study aimed to explore the role of circRNAs in the pathogenesis of CHD and predicted a candidate circRNA that could be targeted for therapeutic approaches to the disease. circRNAs associated with CHD were identified and CHD gene expression profiles were obtained, and analyzed with GEO2R. In addition, differentially expressed miRNA target genes (miR-DEGs) were identified and subjected to functional enrichment analysis. Networks of circRNA/miRNA/mRNA and the miRNA/affected pathways were constructed. Furthermore, a miRNA/mRNA homology study was performed. We identified that hsa_circ_0126672 was strongly associated with the CHD pathology by competing for endogenous RNA (ceRNA) mechanisms. hsa_circ_0126672 characteristically sponges miR-145-5p, miR-186-5p, miR-548c-3p, miR-7-5p, miR-495-3p, miR-203a-3p, and miR-21. Up-regulation of has_circ_0126672 affected various CHD-related cellular functions, such as atherosclerosis, JAK/STAT, and Apelin signaling pathways. Our results also revealed a perfect and stable interaction for the hybrid of miR-145-5p with NOS1 and RPS6KB1. Finally, miR-145-5p had the highest degree of interaction with the validated small molecules. Henchashsa_circ_0126672 and target miRNAs, notably miR-145-5p, could be good candidates for the diagnosis and therapeutic approaches to CHD.

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

Reference87 articles.

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