Dataset Information

Identification of key microRNAs and target genes for the diagnosis of bone nonunion.

ABSTRACT: A number of recent studies have highlighted the causes of bone nonunion (BN), however, the rate of BN incidence continues to rise and available therapeutic options to treat this condition remain limited. Thus, to prevent disease progression and improve patient prognosis, it is vital that BN, or the risk thereof, be accurately identified in a timely manner. In the present study, bioinformatics analyses were used to screen for the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between patients with BN and those with bone union, using data from the Gene Expression Omnibus database. Furthermore, clinical samples were collected and analyzed by reverse transcription?quantitative PCR and western blotting. In vitro and in vivo experiments were carried out to confirm the relationship between BN and the DEGs of interest, in addition to being used to explore the underlying molecular mechanism of BN. Functional enrichment analysis of the downregulated DEGs revealed them to be enriched for genes associated with 'ECM?receptor interactions', 'focal adhesion', 'and the calcium signaling pathway'. When comparing DEM target genes with these DEGs, nine DEGs were identified as putative DEM targets, where hsa?microRNA (miR)?1225?5p?CCNL2, hsa?miR?339?5p?PRCP, and hsa?miR?193a?3p?mitogen?activated protein kinase 10 (MAPK10) were the only three pairs which were associated with decreased gene expression levels. Furthermore, hsa?miR?193a?3p was demonstrated to induce BN by targeting MAPK10. Collectively, the results of the present study suggest that hsa?miR?193a?3p may be a viable biomarker of BN.

SUBMITTER: Xiong Y

PROVIDER: S-EPMC7057810 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Identification of key microRNAs and target genes for the diagnosis of bone nonunion.

Xiong Yuan Y Cao Faqi F Chen Lang L Yan Chenchen C Zhou Wu W Chen Yanyan Y Endo Yori Y Leng Xingzhu X Mi Bobin B Liu Guohui G

Molecular medicine reports 20200221 4

A number of recent studies have highlighted the causes of bone nonunion (BN), however, the rate of BN incidence continues to rise and available therapeutic options to treat this condition remain limited. Thus, to prevent disease progression and improve patient prognosis, it is vital that BN, or the risk thereof, be accurately identified in a timely manner. In the present study, bioinformatics analyses were used to screen for the differentially expressed genes (DEGs) and differentially expressed ...[more]

PMID: 32319614

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Project description:Purpose: Recurrent implantation failure (RIF) is an enormous challenge for in vitro fertilization (IVF) clinicians. An understanding of the molecular mechanisms of RIF helps to predict prognosis and develop new therapeutic strategies. The study is designed to identify diagnostic biomarkers for RIF as well as the potential mechanisms underlying RIF by utilizing public databases together with experimental validation. Methods: Two microarray datasets of RIF patients and the healthy control endometrium were downloaded from the Gene Expression Omnibus (GEO) database. First, differentially expressed microRNAs (miRNAs) (DEMs) were identified and their target genes were predicted. Then, we identified differentially expressed genes (DEGs) and selected hub genes through protein-protein interaction (PPI) analyses. Functional enrichment analyses of DEGs and DEMs were conducted. Furthermore, the key DEMs which targeted these hub genes were selected to obtain the key miRNA-target gene network. The key genes in the miRNA-target gene network were validated by a single-cell RNA-sequencing dataset of endometrium from GEO. Finally, we selected two miRNA-target gene pairs for further experimental validation using dual-luciferase assay and quantitative polymerase chain reaction (qPCR). Results: We identified 49 DEMs between RIF patients and the fertile group and found 136,678 target genes. Then, 325 DEGs were totally used to construct the PPI network, and 33 hub genes were selected. Also, 25 DEMs targeted 16 key DEGs were obtained to establish a key miRNA-target gene network, and 16 key DEGs were validated by a single-cell RNA-sequencing dataset. Finally, the target relationship of hsa-miR-199a-5p-PDPN and hsa-miR-4306-PAX2 was verified by dual-luciferase assay, and there were significant differences in the expression of those genes between the RIF and fertile group by PCR (p < 0.05). Conclusion: We constructed miRNA-target gene regulatory networks associated with RIF which provide new insights regarding the underlying pathogenesis of RIF; hsa-miR-199a-5p-PDPN and hsa-miR-4306-PAX2 could be further explored as potential biomarkers for RIF, and their detection in the endometrium could be applied in clinics to estimate the probability of successful embryo transfer.

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Dataset Information

Identification of key microRNAs and target genes for the diagnosis of bone nonunion.

Publications

Identification of key microRNAs and target genes for the diagnosis of bone nonunion.

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