Investigation of long non‑coding RNA expression profiles in patients with post‑menopausal osteoporosis by RNA sequencing

Abstract

The present study aimed to investigate the implication of long non-coding RNA (lncRNA) expression profiles in post-menopausal osteoporosis (PMOP). A total of 10 patients with PMOP and 10 age-matched healthy post-menopausal females as controls were consecutively enrolled. Their peripheral blood mononuclear cells were obtained and lncRNA as well as mRNA expression profiles were detected by RNA sequencing, followed by bioinformatics analyses. The lncRNA expression profiles were able to distinguish patients with PMOP from controls based on principal component analysis and heatmap analysis. In total, 254 upregulated lncRNAs and 359 downregulated lncRNAs were identified in patients with PMOP vs. controls. The top 5 upregulated lncRNAs were RP11-704M14.1, RP11-754N21.1, RP11-408E5.5, ANKRD26P3 and TPTEP1. The top 5 downregulated lncRNAs were RP11-310E22.4, RP11-326K13.4, FABP5P1, SERPINB9P1 and RPL13P2. Based on the interaction of dysregulated lncRNAs and mRNAs by RNA sequencing, functional annotations were then performed. Gene Ontology enrichment analysis revealed that the dysregulated lncRNAs were enriched in terms including apoptotic process and positive regulation of NF-κB transaction, and Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment in PMOP-associated signaling pathways, including osteoclast differentiation, tumor necrosis factor signaling pathway and mitogen-activated protein kinase signaling pathway. In addition, the regulatory network and circos graph further indicated the implication of lncRNA expression profiles in PMOP via interactions with mRNAs. In conclusion, the present study suggested that aberrant lncRNA expression is deeply involved in the pathogenesis of PMOP by affecting osteoclast differentiation, inflammation and apoptotic processes.

T2DB: A Web Database for Long Non-Coding RNA Genes in Type II Diabetes

“…Although some differentially expressed genes were shared between T2D and control samples ( Figure 3 B), 181 up- and 179 down-regulated genes were differentially regulated specifically in T2D compared to the control samples, including 35 up- and 22 down-regulated lncRNA genes ( Supplementary Table S6 ). Among these up-regulated lncRNA genes, only the following nine have been previously studied: (1) ENSG00000232855 (novel transcript) [ 75 ]; (2) ENSG00000272512 (novel transcript) [ 76 ]; (3) KCNJ2 antisense RNA 1 (KCNJ2-AS1) [ 77 , 78 , 79 ]; (4) KLHDC7B divergent transcript (KLHDC7B-DT) [ 80 , 81 , 82 ]; (5) long intergenic non-protein-coding RNA 2015 (LINC02015) [ 83 , 84 ]; (6) long intergenic non-protein-coding RNA 2381 (LINC02381) [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]; (7) long intergenic non-protein-coding RNA 2541 (LINC02541) [ 94 ]; (8) serpin family B member 9 pseudogene 1 (SERPINB9P1) [ 95 , 96 , 97 ]; and (9) USP30 antisense RNA 1 (USP30-AS1) [ 98 , 99 , 100 ]. However, only the functions of the lncRNA genes LINC02381 and USP30_AS1 are known, with the former known to bind transcription factors [ 85 ], RNA-binding proteins [ 86 ], and miRNAs [ 87 , 88 , 89 , 90 , 91 , 92 , 93 ]; while USP30-AS1 acts as a miRNA sponge [ 98 , 99 ] and is involved in the cis-regulation of the nearby protein-coding genes USP30 and ANKRD13A [ 100 ].…”

A Genome-Wide Association Study for Hypertensive Kidney Disease in Korean Men

“…The rs142696488 variant of the PABPC4L gene indicated the highest significance (discovery, p = 1.17 × 10 −5 ; combination, p = 5.54 × 10 −7 ) with HKD, but it did not show a strong LD with surrounding SNPs at the 4q28.3 position ( Table 2 , Figure S2 ). The ANKRD26P3 gene (near LINC00421 gene) at the 13q12.11 position was associated with post-menopausal osteoporosis [ 33 ] and large artery atherosclerosis (LAA) [ 34 ]. LAA is a systemic disease that narrows arteries due to risk factors such as hypertension, diabetes and hyperlipidemia [ 35 ].…”

Non‐coding RNAs and their cross‐talks impacting reproductive health of women

“…Other than miRNAs, lncRNAs are also involved in PMOP. An RNA sequencing study reported differentially expressed lncRNAs and mRNAs in patients with PMOP (Fei et al, 2018; Wang, 2020). Lnc‐AK077216 was found to be upregulated in PMOP, which is involved in osteoclast differentiation and function with overexpression of osteoclast marker genes such as NFATc1 and CTSK (C. Liu, Cao, et al, 2019).…”