Interaction networks among miRNAs, proteins and metabolites fingerprints identify the regulatory networks and key players in the pathogenesis of diabetic cardiomyopathy

Bhaswati Chatterjee^1*Suman S Thakur²

• ¹National Institute of Animal Biotechnology (NIAB), Hyderabad, India
• ²Centre for Cellular & Molecular Biology (CCMB), Hyderabad, Andhra Pradesh, India

Diabetic cardiomyopathy (DCM) is a complication of diabetes and is the main cause of death in diabetic patients. The regulatory networks and key players involved in the pathogenesis of diabetic cardiomyopathy are not clearly known. We selected the miRNAs, proteins and metabolites fingerprints that were playing a significant role in the DCM and manually constructed miRNA-protein-metabolite interaction networks from miRNA-protein and protein-metabolite interaction networks. Further, protein-protein, metabolite-metabolite and protein-metabolite interaction networks were also constructed. The miRNA-protein interaction included evidence from tarbase and microarrays/ HITS-CLIP. The protein-protein, metabolite-metabolite and protein-metabolite interaction networks were obtained at high confidence scores (≥0.7 or 70%). We proposed that the miRNA-protein-metabolite interaction networks along with their intra- and inter-connected protein-protein, metabolite-metabolite and protein-metabolite interaction networks formed by miRNAs, proteins and metabolites fingerprints such as hsa-mir-122-5p, hsa-mir-30c-5p, hsa-mir-30d-5p, hsa-mir-22-3p, IL6, GSTM2, GPX3, ACADM, GSTM3, LEP, ADIPOQ, INS, CASP1, NLRP3, HADH, ACAT1, PRDX2, PRDX1, TNF, ELAVL1, SERPINA1, A2M, IGFBP7, PRDX6, APOA1, APCS, NPPA, ADAM9, GDF15, ACADVL, ECH1, FGL1, bilirubin, butyric acid (butyrate), octanoylcarnitine (octanoylcarnit.), isoleucine, leucine, alanine, glutamine, L-valine, cytidine triphosphate (ara-CTP), 7-Keto-8-aminopelargonic acid (7-keto-8-amino.), creatinine, decanoylcarnitine (decanoylcarnit.) and hexanoylcarnitine (hexanoylcarnit.) form the key players and the regulatory networks involved in the pathogenesis of DCM. Notably, we also proposed that the interaction networks formed by miRNA, proteins and metabolites fingerprints involved in the early stage of DCM such as hsa-mir-122-5p, IL6, FGL1, LEP, ADIPOQ, INS, TNF, IGFBP7, GDF15, GPX3, NPPA, bilirubin, butyric acid (butyrate) and creatinine are the potential biomarkers and therapeutic targets for the early stage of DCM. To the best of our knowledge, this is the first study of the construction of miRNA-protein-metabolite interactomes in DCM, providing insight into the pathogenesis of DCM.