LncRNA-miRNA-mRNA expression variation profile in the urine of calcium oxalate stone patients

Abstract

Background To explore long-non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) expression profiles and their biological functions in the urine samples in calcium oxalate (CaOx) patients. Methods Five CaOx kidney stone patients were recruited in CaOx stone group and six healthy people were included as control group, whose midstream morning urine was collected before the patients were given any medicine on admission. After total RNA was extracted from urine, microarray of miRNA, mRNA and lncRNA were applied to explore their expression variation. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to reveal the gene functions of the dysregulated lncRNA-associated competing endogenous RNA (ceRNA) network. Quantitative real-time PCR were performed on HK-2 cells treated with sodium oxalate (NaOx) to further screen out the differentially expression profiles of these RNAs. Results A total of nine miRNAs, 883 mRNAs and 1002 lncRNAs were differentially expressed in urine of CaOx patients compared with normal population. GO analysis revealed that most of mRNAs from ceRNA network were enriched in terms of respiratory burst, regulation of mitophagy, and protein kinase regulator activity. KEGG pathway analysis of these genes related to ceRNA network highlight their critical role in pentose phosphate pathway, glyoxylate and dicarboxylate metabolism, and Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. Five miRNAs (miR-6796-3p, miR-30d-5p, miR-3192–3p, miR-518b and miR-6776-3p), four mRNAs (NT5E, CDH4, CLEC14A, CCNL1) and six lncRNAs (lnc-TIGD1L2–3, lnc-KIN-1, lnc-FAM72B-4, lnc-EVI5L-1, lnc-SERPINI1–2, lnc-MB-6) from the HK-2 cells induced by NaOx were consistent with the expression changes of microarray results. Conclusion The differential expressed miRNAs, mRNAs and lncRNAs may be associated with numerous variations of the signaling pathways or regulation of metabolism and kinase activity, providing potential biomarkers for early diagnosis of urolithiasis and new basis for further research of urolithiasis mechanism. Electronic supplementary material The online version of this article (10.1186/s12920-019-0502-y) contains supplementary material, which is available to authorized users.

LncRNA‐ES3 inhibition by Bhlhe40 is involved in high glucose–induced calcification/senescence of vascular smooth muscle cells

“…[36][37][38] These data suggest that proproliferation processes are dysregulated in T2DM and that miR-95 may contribute to this alteration. A recent study 41 found that lnc-RDH8-4:1 may regulate miR-6776-cadherin 4 interactions in patients with calcium oxalate stones, which can activate c-Jun NH(2)-terminal kinase (JNK) signaling pathways in osteosarcoma cells and induce the production of reactive oxygen species (ROS). [39][40][41] Notably, the production of high levels of ROS, which is associated with aging, has been demonstrated to be critical for the induction and maintenance of cellular senescence.…”

“…A recent study 41 found that lnc-RDH8-4:1 may regulate miR-6776-cadherin 4 interactions in patients with calcium oxalate stones, which can activate c-Jun NH(2)-terminal kinase (JNK) signaling pathways in osteosarcoma cells and induce the production of reactive oxygen species (ROS). [39][40][41] Notably, the production of high levels of ROS, which is associated with aging, has been demonstrated to be critical for the induction and maintenance of cellular senescence. 42 MiR-3620 has been reported to regulate the cell cycle, hypoxia, and zinc binding, as well as to play a key role in macrophage dysfunction.…”

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

“…Replication using independent samples and a different wet-lab experimental approach supported the association of CCNL1 with DKD. Based on published gene expression data from the Affymetrix ® GeneChip ® Whole Transcript Expression Arrays, CCNL1 was one of four genes differentially expressed in patients with kidney stones compared to controls (2.6 fold change, downregulated, P = 6.58E-05) ( Liang et al, 2019 ). Based on gene expression data within NephroSeq, differential gene expression was observed for CCNL1 in kidney biopsy tissues from people with kidney disease compared to controls ( Gunther et al, 2014 ; Ju et al, 2015 ; Nakagawa et al, 2015 ); no adjustment was made for cell heterogeneity in the disease compared to control collections for these gene expression datasets.…”

The Preventive Effect of Cardiac Sympathetic Denervation Induced by 6-OHDA on Myocardial Ischemia–Reperfusion Injury: The Changes of lncRNA/circRNAs-miRNA-mRNA Network of the Upper Thoracic Spinal Cord in Rats

“…The spinal samples from the two groups were selected for microarray analysis. We used the Affymetrix® GeneChip® Whole Transcript Expression Arrays to analyze lncRNA and mRNA expression profiles, and we applied Agilent circRNA Microarray 8x60K to analyze circRNA expression profiles in the T1–T4 spinal cord segments [ 34 ]. Microarray data were obtained and analyzed by Oebiotech Corporation (Shanghai, China).…”