Screening potential prognostic biomarkers of long non-coding RNAs for predicting the risk of chronic kidney disease

Abstract

Not much is known about the roles of long non-coding RNAs (lncRNAs) for chronic kidney disease (CKD). In this study, we included CKD patient cohorts and normal controls as a discovery cohort to identify putative lncRNA biomarkers associated with CKD. We first compared the lncRNA expression profiles of CKD patients with normal controls, and identified differentially expressed lncRNAs and mRNAs. Co-expression network based on the enriched differentially expressed mRNAs and lncRNAs was constructed using WGCNA to identify important modules related to CKD. A lncRNA-miRNA-mRNA pathway network based on the hub lncRNAs and mRNAs, related miRNAs, and overlapping pathways was further constructed to reveal putative biomarkers. A total of 821 significantly differentially expressed mRNAs and lncRNAs were screened between CKD and control samples, which were enriched in nine modules using weighted correlation network analysis (WGCNA), especially brown and yellow modules. Co-expression network based on the enriched differentially expressed mRNAs and lncRNAs in brown and yellow modules uncovered 7 hub lncRNAs and 53 hub mRNAs. A lncRNA-miRNA-mRNA pathway network further revealed that lncRNAs of HCP5 and NOP14-AS1 and genes of CCND2, COL3A1, COL4A1, and RAC2 were significantly correlated with CKD. The lncRNAs of NOP14-AS1 and HCP5 were potential prognostic biomarkers for predicting the risk of CKD.

LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis

“…Numerous studies introduced that HCP5 overexpression promoted cancer cell malignant behaviors, such as epithelial-mesenchymal transition (EMT), proliferation, migration, invasion and angiogenic ability [ 12 , 13 , 20 ], suggesting the vital role of HCP5 in cancer initiation and progression. Besides, HCP5 expression was previously shown to be increased in CKD patients compared to normal control [ 14 ], hinting that HCP5 might participate in kidney-associated diseases. Consistently, our data, for the first time, found that the expression of HCP5 was notably enhanced in serum samples from DN patients and HG-treated HGMCs.…”

“…LncRNA HLA complex P5 (HCP5) was a well-acknowledged oncogenic driver in various cancers [ 12 , 13 ]. Besides, HCP5 was proposed to be one of the potential prognostic biomarkers for predicting the risk of chronic kidney disease (CKD) [ 14 ]. However, no studies reported the role of HCP5 in DN.…”

Non-Coding RNAs in Kidney Diseases: The Long and Short of Them

“…Another study published in 2019 found that lncRNAs NOP14-AS1 and HCP5 were potential prognostic biomarkers in CKD [ 84 ]. They first compared the expression profiles of several lncRNAs in healthy individuals and CKD patients with normal controls.…”

Transforming Growth Factor-β and Long Non-coding RNA in Renal Inflammation and Fibrosis

“…Based on the cell type-, tissue- and disease stage-dependent specialties, lncRNA may also present as biomarkers for clinical diagnosis in renal diseases ( Brandenburger et al, 2018 ; Cheng et al, 2019 ; Li et al, 2019 ; Liu et al, 2019b ; Loganathan et al, 2020 ). Interestingly, lncRNAs are relevant biomarkers for disease due to their existence with proteins or in vesicles in the extracellular space under pathological conditions ( Teng and Ghoshal, 2015 ; Ellinger et al, 2016 ; Zhang et al, 2017c ; E, S., Costa et al, 2018 ; Sarfi et al, 2019 ).…”