Identification of the specific microRNAs and competitive endogenous RNA mechanisms in osteoporosis

Abstract

Objective: Osteoporosis and osteoarthritis are metabolic skeletal disorders. This study aimed to identify specific networks of competitive endogenous RNA (ceRNA) in osteoporosis that differ from those in osteoarthritis.

Methods: The dataset GSE74209 was downloaded from the Gene Expression Omnibus, and differentially expressed microRNAs (DEmiRNAs) in osteoporotic samples and osteoarthritic samples were identified. After predicting target genes and linked long noncoding (lnc)RNAs, ceRNA networks of DEmiRNAs were constructed. The nodes that overlapped between ceRNA networks and the Comparative Toxicogenomics Database were selected as key candidates.

Results: Fifteen DEmiRNAs (including 2 downregulated and 13 upregulated miRNAs) were identified in osteoporotic samples versus osteoarthritic samples; these targeted 161 genes and linked to 60 lncRNAs. The ceRNA network consisted of 6 DEmiRNAs, 63 target genes, and 53 lncRNAs. After searching the Comparative Toxicogenomics Database and mining the literature, 2 lncRNAs (MALAT1 and NEAT1), 2 DEmiRNAs (hsa-miR-32-3p, downregulated; and hsa-miR-22-3p, upregulated) and 6 genes (SP1, PTEN, ESR1, ERBB3, CSF1R, and CDK6) that relate to cell death, growth, and differentiation were identified as key candidates separating osteoporosis from osteoarthritis.

Conclusions: Two miRNA-ceRNA networks (including NEAT1/MALAT1-hsa-miR-32-3p-SP1/FZD6 and NEAT1/MALAT1-hsa-miR-22-3p-PTEN/ESR1/ERBB3/CSF1R/CDK6) might have crucial and specific roles in osteoporosis.

Keywords: Osteoarthritis; Wnt/β-catenin pathway; competitive endogenous RNA; interleukin-6; microRNA; osteoporosis.

Figure 1.

Heatmap illustrating expression profiles of differentially expressed microRNAs (miRNAs) in osteoarthritis and osteoporosis. Red and blue colors indicate high and low expression of miRNA, respectively.

Figure 2.

The microRNA (miRNA)–target regulatory network. Triangles and circles represent miRNA and target genes, respectively.

Figure 3.

Competing endogenous RNA (ceRNA) network in osteoporosis. Diamonds, triangles, and circles indicate long noncoding (lnc)RNA, microRNA (miRNA), and target genes, respectively. The key candidates are shown in a larger font.

Figure 4.

Functional clustering of key candidates using literature mining. Green and black indicate that the corresponding gene-term association was positively and negatively reported, respectively. Criteria were hit ≥8, enrichment score >5.0 and p < 1e−04.