Identifying the Potential Differentially Expressed miRNAs and mRNAs in Osteonecrosis of the Femoral Head Based on Integrated Analysis

Hao, You-Zeng; Lü, Chao; Zhang, Baogang; Xu, Zhaochen; Guo, Hao; Zhang, Gaokui

doi:10.2147/cia.s289479

Cited by 9 publications

(9 citation statements)

References 82 publications

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“…miR-148a-3p [ 17 ], miR-23b-3p [ 18 ], and miR-26a [ 19 ] were all reported to play a protective role against ONFH. Recent advancement of genome-wide profiling approaches, such as gene microarray and RNA-sequencing technology, enhances the understanding of miRNA and gene expression profiles in the context of ONFH, providing opportunity to identify novel biomarkers and therapeutic targets for ONFH [ 20 , 21 ]. However, previous miRNA and gene expression profiles studies in ONFH are limited and focused one or several of the differentially expressed miRNAs (DEmiRs) or differential expressed genes (DEGs); none of them focused on the cooperative miRNA-mRNA regulatory mechanism for the pathogenesis of ONFH.…”

Section: Introductionmentioning

confidence: 99%

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

Yu¹,

Yao

Jiang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Osteonecrosis of the femoral head (ONFH) accounts for as many as 18% of total hip arthroplasties. Knowledge of genetic changes and molecular abnormalities could help identify individuals considered to be at a higher risk of developing ONFH. In this study, we sought to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) associated with ONFH by integrated bioinformatics analyses as well as to construct the miRNA-mRNA regulatory network involving in the pathogenesis of ONFH. We performed differential expression analysis using a gene expression profile GSE123568 and a miRNA expression profile GSE89587 deposited in the Gene Expression Omnibus and identified 47 DEmiRs (24 upregulated miRNAs and 23 downregulated miRNAs) and 529 DEGs (218 upregulated genes and 311 downregulated genes). Gene Ontology enrichment analyses of DEGs suggested that DEGs were significantly enriched in neutrophil activation, cytosol, and ubiquitin-protein transferase activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs revealed that DEGs were significantly enriched in transcriptional misregulation in cancer. DEGs-based miRNA-mRNA regulatory networks were obtained by searching miRNA-mRNA prediction databases, TargetScan, miTarBase, miRMap, miRDB, and miRanda databases. Then, overlapped miRNAs were selected between these putative miRNAs and DEmiRs between ONFH and non-ONFH, and pairs of the DEmiR-DEG regulatory network were finally depicted. There were 12 nodes and 64 interactions for upDEmiR-downDEG regulatory networks and 6 nodes and 16 interactions for downDEmiR-upDEG regulatory networks. Using the STRING database, we established a protein-protein interaction network based on the overlapped DEGs between ONFH and non-ONFH. C5AR1, CDC27, CDC34, KAT2B, CPPED1, TFDP1, and MX2 were identified as the hub genes. The present study characterizes the miRNA profile, gene profile, and miRNA-mRNA regulatory network in ONFH, which may contribute to the interpretation of the pathogenesis of ONFH and the identification of novel biomarkers and therapeutic targets for ONFH.

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Section: Introductionmentioning

confidence: 99%

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

Yu¹,

Yao

Jiang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Hao et al [ 99 ] identified 24 differentially-expressed miRNAs associated with 457 mRNAs in blood samples of ONFH individuals; some of the most representative upregulated miRNAs were hsa-miR-378c, hsa-miR-3200-3p, hsa-miR-28-5p, hsa-let-7a-5p, hsa-miR-3200-5p, and hsa-miR-532-5p. Moreover, it was observed that hsa-miR-378-c could downregulate WNT3A, DACT1, and CSF1, suggesting its possible role in regulating angiogenesis and bone remodeling.…”

Section: Osteonecrosis and Mirnasmentioning

confidence: 99%

“…Likewise, it was suggested that hsa-let-7a-5p could have a crucial role in ONFH progression due to the fact that this miRNA targets RCAN2 and IL9R, which are proteins involved in bone development and hematopoietic cell lineage, correspondingly. Finally, it was demonstrated that hsa-miR-532-5p could hinder the expression of CLDN18 and CLDN10 ( Figure 4 ), which might be implicated in ONFH bone loss [ 99 ].…”

Section: Osteonecrosis and Mirnasmentioning

confidence: 99%

The Emerging Role of MicroRNAs in Bone Diseases and Their Therapeutic Potential

et al. 2021

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MicroRNAs (miRNAs) are a class of small (20–24 nucleotides), highly conserved, non-coding RNA molecules whose main function is the post-transcriptional regulation of gene expression through sequence-specific manners, such as mRNA degradation or translational repression. Since these key regulatory molecules are implicated in several biological processes, their altered expression affects the preservation of cellular homeostasis and leads to the development of a wide range of pathologies. Over the last few years, relevant investigations have elucidated that miRNAs participate in different stages of bone growth and development. Moreover, the abnormal expression of these RNA molecules in bone cells and tissues has been significantly associated with the progression of numerous bone diseases, including osteoporosis, osteosarcoma, osteonecrosis and bone metastasis, among others. In fact, miRNAs regulate multiple pathological mechanisms, including altering either osteogenic or osteoblast differentiation, metastasis, osteosarcoma cell proliferation, and bone loss. Therefore, in this present review, aiming to impulse the research arena of the biological implications of miRNA transcriptome in bone diseases and to explore their potentiality as a theragnostic target, we summarize the recent findings associated with the clinical significance of miRNAs in these ailments.

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“…Zhang, Chen, et al, 2018), and it has been tested to be related with osteogenic differentiation (Guo et al, 2020). As reported, miR-532-5p is upregulated in ONFH (Hao et al, 2021); however, its role and molecular mechanism in ONFH still need to be further explored.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells‐derived exosomes mediate nuclear receptor coactivator‐3 expression in osteoblasts by delivering miR‐532‐5p to influence osteonecrosis of the femoral head development

Lan

Xiong

et al. 2022

Cell Biology International

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Exosomes (Exo) originated from bone marrow mesenchymal stem cells (BMSCs) have therapeutic impacts on osteonecrosis of the femoral head (ONFH), and microRNA (miR)-532-5p has been confirmed to participate in ONFH progression. In the research, it was figured out whether BMSCs-Exo could relieve ONFH by delivering miR-532-5p. MG-63 cells were treated with DEX to construct an ONFH cell model in vitro. The effects of Exo and miR-532-5p on the cell viability, lactate dehydrogenase (LDH) content, and apoptosis of BMSCs were detected. The ONFH rat model was established, and the effect of BMSCs-Exo delivering miR-532-5p on the pathological damage of ONFH rats was evaluated. Changes in nuclear receptor coactivator-3 (NCOA3) and apoptotic proteins were assessed by western blot. The relationship between miR-532-5p and NCOA3 was verified by dual luciferase reporter experiments. miR-532-5p was elevated in vivo and in vitro ONFH-models, while NCOA3 expression was reduced. Overexpression of miR-532-5p aggravated DEX toxicity in osteoblasts, decreased cell viability, and promoted apoptosis. Knockdown of miR-532-5p made Exo further attenuate the toxic effect of DEX on osteoblasts and inhibited apoptosis. The protective effect of miR-532-5p-delivering Exo on osteoblasts was reversed by NCOA3 silencing. In addition, in vivo experiments also confirmed that knockdown of miR-532-5p enhanced the therapeutic effect of Exo on ONFH rats. This study demonstrates that miR-532-5p-delivering BMSCs-Exo inhibits osteoblast viability and promote apoptosis by targeting NCOA3, thereby aggravating ONFH development.

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Identifying the Potential Differentially Expressed miRNAs and mRNAs in Osteonecrosis of the Femoral Head Based on Integrated Analysis

Cited by 9 publications

References 82 publications

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

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

The Emerging Role of MicroRNAs in Bone Diseases and Their Therapeutic Potential

Bone marrow mesenchymal stem cells‐derived exosomes mediate nuclear receptor coactivator‐3 expression in osteoblasts by delivering miR‐532‐5p to influence osteonecrosis of the femoral head development

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