MicroRNA sequence analysis of plasma exosomes in early Legg–Calvé–Perthes disease

Huang, Qian; Li, Boxiang; Lin, Chengsen; Chen, Xianxiang; Wang, Tiantian; Liu, Jianhong; Liu, Yun; Lu, Rongbin; Liao, Shijie; Ding, Xiaofei

doi:10.1016/j.cellsig.2021.110184

Cited by 6 publications

(5 citation statements)

References 47 publications

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“…The study showed an increased number of EMPs in the circulation of Perthes patients and suggested that the mechanism of action of these circulating EMPs might be endothelial cell apoptosis, endothelial dysfunction and deregulated angiogenesis in Perthes patients [21]. In a study by Huang et al, epigenetic factors that might contribute to Perthes disease were examined in the plasma exosomes of both Perthes patients and controls [22]. They showed the differential expression of several miRNAs involved in endothelial cell dysfunction (miR-3133, miR-4644, miR-4693-3p and miR-4693-5p) and osteoclastogenesis (miR-3133, miR-4693-3p, miR-4693-5p, miR-141-3p and miR-30a) that might contribute to the development of Perthes disease [22].…”

Section: Plasma Exosomes and Microparticlesmentioning

confidence: 99%

“…In a study by Huang et al, epigenetic factors that might contribute to Perthes disease were examined in the plasma exosomes of both Perthes patients and controls [22]. They showed the differential expression of several miRNAs involved in endothelial cell dysfunction (miR-3133, miR-4644, miR-4693-3p and miR-4693-5p) and osteoclastogenesis (miR-3133, miR-4693-3p, miR-4693-5p, miR-141-3p and miR-30a) that might contribute to the development of Perthes disease [22].…”

Section: Plasma Exosomes and Microparticlesmentioning

confidence: 99%

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Molecular Biomarkers in Perthes Disease: A Review

et al. 2023

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Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.

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Section: Plasma Exosomes and Microparticlesmentioning

confidence: 99%

Section: Plasma Exosomes and Microparticlesmentioning

confidence: 99%

Molecular Biomarkers in Perthes Disease: A Review

et al. 2023

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“…Frontiers in Genetics frontiersin.org approaches (Huang et al, 2022;Wang et al, 2022). The present study therefore aimed to perform whole-transcriptome sequencing combined with miRNA sequencing for analyzing the gene expression patterns in Perthes disease.…”

Section: Figurementioning

confidence: 99%

“…Huang et al identified 35 differentially expressed miRNAs (DEmiRNAs) in early Perthes disease by miRNA sequencing using plasma exosomes. Notably, the study revealed that the expression levels of has-miR-3133, has-miR-4644, has-miR-150-5p, and hsa-miR-4693-3p were significantly increased in the plasma exosomes, and that the MAPK, Ras, cAMP, and PI3K-Akt signaling pathways were involved in disease pathogenesis (Huang et al, 2022). The ceRNA hypothesis describes a comprehensive regulatory mechanism between coding and non-coding RNAs (Tay et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Construction of ceRNA network based on RNA-seq for identifying prognostic lncRNA biomarkers in Perthes disease

Zhang

et al. 2023

Front. Genet.

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Introduction: Legg-Calvé-Perthes disease or Perthes disease is a condition that occurs in children aged 2 to 15 years, and is characterized by osteonecrosis of the femoral head, which results in physical limitations. Despite ongoing research, the pathogenesis and molecular mechanisms underlying the development of Perthes disease remain unclear. In order to obtain further insights, the expression patterns of long non-coding RNAs (lncRNAs), miRNAs, and mRNAs in a rabbit model of Perthes disease were analyzed in this study by transcriptome sequencing.Methods and results: The results of RNA-seq analyses revealed that 77 lncRNAs, 239 miRNAs, and 1027 mRNAs were differentially expressed in the rabbit model. This finding suggested that multiple genetic pathways are involved in the development of Perthes disease. A weighted gene co-expression network analysis (WGCNA) network was subsequently constructed using the differentially expressed mRNAs (DEmRNAs), and network analysis revealed that the genes associated with angiogenesis and platelet activation were downregulated, which was consistent with the findings of Perthes disease. A competing endogenous RNA (ceRNA) network was additionally constructed using 29 differentially expressed lncRNAs (including HIF3A and LOC103350994), 28 differentially expressed miRNAs (including ocu-miR-574-5p and ocu-miR-324-3p), and 76 DEmRNAs (including ALOX12 and PTGER2).Disscusion: The results obtained herein provide novel perspectives regarding the pathogenesis and molecular mechanisms underlying the development of Perthes disease. The findings of this study can pave the way for the development of effective therapeutic strategies for Perthes disease in future.

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“…The altered miRNA expressions are key controls on gene behavior, contributing to the development of inflammatory conditions [10]. For example, Legg-Calvé-Perthes is an inflammatory disease with high expression of miR-4693-5p that promotes endothelial cell dysfunction and osteoclastogenesis [11]. In another report, miR-4693-5p targeted thyroid hormone receptor-interacting protein 13 (TRIP) 13 to promote apoptosis and suppress cell proliferation [12].…”

Section: Introductionmentioning

confidence: 99%

Functional Significance of miR-4693-5p in Targeting HIF1α and Its Link to Rheumatoid Arthritis Pathogenesis

Saquib,

Agnihotri,

Sarkar

et al. 2024

ncRNA

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes joint inflammation and destruction with an unknown origin. Our study aims to elucidate the molecular mechanism behind HIF1α overexpression in RA. Dysregulated miRNA expressions are known to influence gene behavior, thereby enhancing cell proliferation, inflammation, and resistance to apoptosis, contributing to RA development. Our earlier finding indicated that exogenous miRNA similar to miR-4693-5p may modulate RA-related targets. However, the specific role of miR-4693-5p and its targets in RA remain unexplored. In this study, we found that miR-4693-5p was significantly reduced in PBMCs of RA patients, with evidence suggesting it targets the 3′ UTR of HIF1α, thereby potentially contributing to its overexpression in RA. In vitro overexpression of miR-4693-5p leads to the knockdown of HIF1α, resulting in inhibited expression of Survivin to disrupt apoptosis resistance, inflammation suppression, and a reduction in the total cellular ROS response in SW982 and RAFLS cells. The results were validated using the CIA Rat model. In conclusion, this study provides a crucial foundation for understanding the functional role of miR-4693-5p. These findings improve our understanding and provide novel insights into the molecular mechanisms underlying RA pathogenesis.

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MicroRNA sequence analysis of plasma exosomes in early Legg–Calvé–Perthes disease

Cited by 6 publications

References 47 publications

Molecular Biomarkers in Perthes Disease: A Review

Molecular Biomarkers in Perthes Disease: A Review

Construction of ceRNA network based on RNA-seq for identifying prognostic lncRNA biomarkers in Perthes disease

Functional Significance of miR-4693-5p in Targeting HIF1α and Its Link to Rheumatoid Arthritis Pathogenesis

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