Gene expression profile analysis unravelled the systems level association of renal cell carcinoma with diabetic nephropathy and Matrix-metalloproteinase-9 as a potential therapeutic target

Abstract

Type 2 diabetes (T2D) and cancer share many common risk factors. However, the potential biological link that connects the two at the molecular level is still unclear. The experimental evidence suggests that several genes and their pathways may be involved in developing cancerous conditions associated with diabetes. In this study, we identified the protein-protein interaction (PPI) networks and the hub protein(s) that interlink T2D and cancer using genome-scale differential gene expression profiles. Further, the PPI network of AMP-activated protein kinase (AMPK) in cancer was analyzed to explore novel insights into the molecular association between the two conditions. The densely connected regions were analyzed by constructing the backbone and subnetworks with key nodes and shortest pathways, respectively. The PPI network studies identified Matrix-metalloproteinase-9 (MMP-9) as a hub protein playing a vital role in glomerulonephritis tubular diseases and some genetic kidney diseases. MMP-9 was also associated with different growth factors, like tumor necrosis factor (TNF-α), transforming growth factor 1 (TGF-1), and pathways like chemokine signaling, NOD-like receptor signaling, etc. Further, the molecular docking and molecular dynamic simulation studies supported the druggability of MMP-9, suggesting it as a potential therapeutic target in treating renal cell carcinoma linked with diabetic kidney disease. Communicated by Ramaswamy H. Sarma