Identification of key lncRNAs contributing to diabetic nephropathy by gene co-expression network analysis

LncRNA is reported to have important role in diabetic nephropathy (DN). Here, we aim to identify key lncRNAs of DN using bioinformatics and systems biological methods.

Five microarray data sets from Gene Expression Omnibus (GEO) database were included. Probe sets were re-annotated. In the training set, differential expressed genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was constructed to screen diabetic-related hub genes and reveal their potential biological function. Two more human data sets and mouse data sets were used as validation sets.

A total of 424 DEGs, including 10 lncRNAs, were filtered in the training data set. WGCNA and enrichment analysis of hub genes showed that inflammation and metabolic disorders are prominent in DN. Three key lncRNAs (NR_130134.1, NR_029395.1 and NR_038335.1) were identified. These lncRNAs are also differently expressed in another two human data sets. Functional enrichment of the mouse data sets showed consistent changes with that in human, indicating similar changes in gene expression pattern of DN and confirmed confidence of our analysis. Human podocytes and mesangial cells were culture in vitro. QPCR and fluorescence in situ hybridization were taken out to validate the expression and relationship of key lncRNAs and their related mRNAs. Results were also consistent with our analysis.

Inflammation and metabolic disorders are prominent in DN. We identify three lncRNAs that are involved in these processes possibly by interacting with co-expressed mRNAs.