Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head

Yu, Lu; Yao, Tengfei; Jiang, Zhoulei; Xu, Tong

doi:10.1155/2021/8076598

Cited by 8 publications

(10 citation statements)

References 38 publications

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“…CPPED1 is a member of calcineurin‐like metallophosphoesterase superfamily involving in the timing of birth and spontaneous delivery 13,14 . It was disclosed that CPPED1 might be associated with the pathogenesis of osteonecrosis of the femoral head 15 . Even though the impact of CPPED1 in restenosis after PCI has barely been discussed before, it was known from the microarray data in our study that CPPED1 and SP1 were both highly expressed in the serum of patients with restenosis.…”

Section: Introductionmentioning

confidence: 64%

The potential function of SP1 and CPPED1 in restenosis after percutaneous coronary intervention

Wang

Liang

Cai

et al. 2022

Journal of Cardiac Surgery

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Objectives Impacts of molecular pathways have been discussed recently on restenosis after percutaneous coronary intervention (PCI). Hence, this study aimed to explore the impact of calcineurin‐like phosphoesterase domain containing 1 (CPPED1) and specificity protein 1 (SP1) on restenosis after PCI. Methods A carotid balloon injury rat model was established, followed by western blot analysis of SP1 and CPPED1 expression in carotid artery (CA) tissues. After SP1 and CPPED1 were overexpressed, the neointimal hyperplasia and luminal stenosis were assessed. In addition, EPC underwent hypoxia/reoxygenation (H/R) treatment to construct an endothelial injury cell model. Then, cell proliferation, apoptosis, intracellular reactive oxygen species (ROS), and Ca2+ concentration were detected with cell counting kit‐8 (CCK‐8), flow cytometry, Chloromethyl‐2'7'‐dichlorofluorescein diacetate (CM‐H2DCFDA) penetrant, and Fluo‐4 AM staining, respectively. The binding relationship between SP1 and CPPED1 was verified by dual‐luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Results SP1 and CPPED1 were lowly expressed in the model rats with carotid balloon injury. Mechanistically, SP1 bound to the promoter region of CPPED1 to activate CPPED1 expression. Overexpressing SP1 or CPPED1 lowered neointimal formation and restenosis rate, thus promoting the recovery of carotid balloon injury in rats. Meanwhile, SP1 and CPPED1 upregulation reduced ROS levels, Ca2+ concentration, and apoptosis of EPCs, accompanied by accelerated EPC viability. Conclusions SP1 or CPPED1 overexpression reduced neointimal formation and restenosis rate in carotid balloon injury.

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Section: Introductionmentioning

confidence: 64%

The potential function of SP1 and CPPED1 in restenosis after percutaneous coronary intervention

Wang

Liang

Cai

et al. 2022

Journal of Cardiac Surgery

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“…MiRNAs was an endogenous noncoding RNA molecule of length 20-24nt, which could regulate gene expression and repress translation at the post-transcriptional level of target genes by targeting the 3′UTR region of the mRNA [ 46 , 47 ]. However, the expression level of miRNAs also infected by its upstream molecular lncRNA, which was another noncoding RNA molecule of a transcript greater than 200 bp in length that were no or little translational potential [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

IRF8 and its related molecules as potential diagnostic biomarkers or therapeutic candidates and immune cell infiltration characteristics in steroid-induced osteonecrosis of the femoral head

Liang

Liu

et al. 2023

J Orthop Surg Res

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Purpose Steroid-induced osteonecrosis of the femoral head (SONFH) was a refractory orthopedic hip joint disease in the young and middle-aged people, but the pathogenesis of SONFH remained unclear. We aimed to identify the potential genes and screen potential therapeutic compounds for SONFH. Methods The microarray was obtained for blood tissue from the GEO database, and then it identifies differentially expressed genes (DEGs). The DEGs were analyzed to obtain the differences in immune cell infiltration. The gene functional enrichment analysis of SONFH was analyzed. The PPI of DEGs was identified through the STRING database, and the cluster modules and hub genes were ascertained using MCODE and CytoHubba, and the ROC curve of hub genes was analyzed, and the tissues distribution of hub genes was understood by the HPA, Bgee and BioGPS databases. The hub genes and target miRNAs and corresponding upstream lncRNAs were predicted by TargetScan, miRDB and ENCORI database. Subsequently, we used CMap, DGIdb and L1000FWD databases to identify several potential therapeutic molecular compounds for SONFH. Finally, the AutoDockTools Vina, PyMOL and Discovery Studio were employed for molecular docking analyses between compounds and hub genes. Results The microarray dataset GSE123568 was obtained related to SONFH. There were 372 DEGs including 197 upregulated genes and 175 downregulated genes by adjusted P value < 0.01 and |log2FC|> 1. Several significant GSEA enrichment analysis and biological processes and KEGG pathway associated with SONFH were identified, which were significantly related to cytoskeleton organization, nucleobase-containing compound catabolic process, NOD-like receptor signaling pathway, MAPK signaling pathway, FoxO signaling pathway, neutrophil-mediated immunity, neutrophil degranulation and neutrophil activation involved in immune response. Activated T cells CD4 memory, B cells naïve, B cells memory, T cells CD8 and T cells gamma delta might be involved in the occurrence and development of SONFH. Three cluster modules were identified in the PPI network, and eleven hub genes including FPR2, LILRB2, MNDA, CCR1, IRF8, TYROBP, TLR1, HCK, TLR8, TLR2 and CCR2 were identified by Cytohubba, which were differed in bone marrow, adipose tissue and blood, and which had good diagnostic performance in SONFH. We identified IRF8 and 10 target miRNAs that was utilized including Targetsan, miRDB and ENCORI databases and 8 corresponding upstream lncRNAs that was revealed by ENCORI database. IRF8 was detected with consistent expression by qRT-PCR. Based on the CMap, DGIdb and L1000FWD databases, the 11 small molecular compounds that were most strongly therapeutic correlated with SONFH were estradiol, genistein, domperidone, lovastatin, myricetin, fenbufen, rosiglitazone, sirolimus, phenformin, vorinostat and vinblastine. All of 11 small molecules had good binding affinity with the IRF8 in molecular docking. Conclusion The occurrence of SONFH was associated with a “multi-target” and “multi-pathway” pattern, especially related to immunity, and IRF8 and its noncoding RNA were closely related to the development of SONFH. The CMap, DGIdb and L1000FWD databases could be effectively used in a systematic manner to predict potential drugs for the prevention and treatment of SONFH. However, additional clinical and experimental research is warranted.

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“…Such as using miRNA-mRNA Regulatory Networks to study the pathogenesis of Osteonecrosis of the Femoral Head. 13 However, this research method has not been applied to study the pathogenesis of AMI. In this study, the differentially expressed genes were analyzed by mining the chip data of miRNAs and mRNAs associated with AMI from the GEO database, and then a miRNA-mRNA regulatory relationship network was constructed in the hope of providing data support and a theoretical basis for the occurrence, development and prevention of AMI.…”

Section: Discussionmentioning

confidence: 99%

Screening and Analysis of Potential Critical Gene in Acute Myocardial Infarction Based on a miRNA-mRNA Regulatory Network

Hou¹,

Guo²,

Fan³

et al. 2022

IJGM

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Background MicroRNAs (miRNAs) have been shown to be involved in the initiation, progression, and prevention of acute myocardial infarction (AMI), but the underlying mechanism remains unclear. Objective Through the GEO database, bioinformatics methods were used to explore the miRNA-mRNA regulatory relationship pairs associated with AMI and to elucidate the underlying mechanism. Methods Using the R software Limma package, differential expression analysis was performed using the AMI-related miRNA chip dataset (GSE31568) and mRNA chip dataset (GSE159657) from the GEO database. The miRDB, miRWalk, miRTarBase, and TargetScan databases were used to predict potential downstream target genes regulated by differentially expressed miRNAs, and a miRNA-mRNA regulatory network was built with Cytoscape; GO function and KEGG pathway enrichment analyses of target genes were done with Funrich software, and the protein interaction network of target genes in the regulatory network was built with the STRING database. Results and Conclusions A total of 187 differentially expressed miRNAs were experimentally screened, of which 91 were upregulated (such as hsa-miR-302b, hsa-miR-1299), and 96 were downregulated (such as hsa-miR-1201, hsa-miR-1283); 507 differentially expressed mRNAs were identified, of which 430 were upregulated (such as MRM1 and SFXN4), and 77 were downregulated (such as KCTD13 and CCDC134). And 16 miRNAs and 44 mRNAs were used for regulatory network construction. GO and KEGG enrichment analyses mainly focused on Integrins in angiogenesis, angiopoietin receptor Tie2-mediated signaling, and signaling events mediated by stem cell factor receptor (c-Kit). As hub genes in the PPI network, FGF2 and MMP2 may be key targets of AMI. The experimentally constructed miRNA-mRNA regulatory network found that hsa-miR-190b targets to inhibit FGF2, while hsa-miR-330-3p targets to regulate MMP2, which may mediate Integrins in angiogenesis, Angiopoietin receptor Tie2-mediated signaling pathway to induce AMI pathogenesis, providing strong data support and a research direction for the prevention and treatment of AMI.

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Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head

Cited by 8 publications

References 38 publications

The potential function of SP1 and CPPED1 in restenosis after percutaneous coronary intervention

The potential function of SP1 and CPPED1 in restenosis after percutaneous coronary intervention

IRF8 and its related molecules as potential diagnostic biomarkers or therapeutic candidates and immune cell infiltration characteristics in steroid-induced osteonecrosis of the femoral head

Screening and Analysis of Potential Critical Gene in Acute Myocardial Infarction Based on a miRNA-mRNA Regulatory Network

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