FOXO3 is targeted by miR-223-3p and promotes osteogenic differentiation of bone marrow mesenchymal stem cells by enhancing autophagy

Cheng, Long; Cen, Shiqiang; Zhong, Zhou; Zhou, Chang; Zhong, Gang

doi:10.1007/s13577-020-00421-y

Cited by 26 publications

(17 citation statements)

References 34 publications

(40 reference statements)

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“…The result showed that 13 miRNAs were remarkably highly expressed in PBMC of mice with osteoporosis. Among the 13 miRNAs, the expression trends of miR-1271-5p, miR-135a-5p, miR-135b-5p, miR-153-3p, miR-223-3p, miR-27a-3p, miR-370-3p, and miR-9-5p in the current study were in line with their trends in various studies [5,7,[41][42][43][44][45][46]. Our result revealed that the expression of the 13 miRNAs was positively correlated with the progression of osteoporosis.…”

Section: Discussionsupporting

confidence: 86%

Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches

Lü

Wang

Xue

et al. 2021

Computational and Mathematical Methods in Medicine

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Osteoporosis is a degenerative osteoarthropathy commonly found in old people and postmenopausal women. Many studies showed that microRNAs (miRNAs) can regulate the expression of osteoporosis-related genes and are abnormally expressed in patients with osteoporosis. miRNAs therefore have the potential to serve as biomarkers of osteoporosis. In this study, the limma package was used for the differential expression analysis of mRNA expression profiles and 357 significantly differentially expressed genes (DEGs) were obtained. Metascape was used for functional enrichment analysis of DEGs. The result revealed that DEGs were mainly enriched in signaling pathways like MAPK6/MAPK4. Based on the STRING database, the protein-protein interaction (PPI) network of DEGs was constructed. MCODE was used to analyze the functional subsets, and a key functional subset composed of 9 genes was screened out. In addition, the miRNA-mRNA regulatory interaction network (RegIN) was analyzed by the CyTargetLinker plugin, which generated 55 miRNA-mRNA regulatory interactions. Through literature searching, the osteoporosis-related gene FOXO1 in the key functional subset was determined to be the main object of the study. In qRT-PCR assay, the expression of the predicted miRNAs was tested in peripheral blood mononuclear cells of mice with osteoporosis, in which 13 miRNAs were remarkably highly expressed. All in all, this study, based on bioinformatics analysis and testing assay of miRNA expression, determined the potential biomarkers of osteoporosis.

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Section: Discussionsupporting

confidence: 86%

Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches

Lü

Wang

Xue

et al. 2021

Computational and Mathematical Methods in Medicine

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“…ere are 20 pathways, which are closely related to inflammatory response, oxidative stress, autophagy, apoptosis, and submandibular gland cell signaling. A large number of experimental studies have shown that the FOXO family of transcription factors plays a crucial role in many basic cellular processes such as immune regulation, metabolism, proliferation, apoptosis, and oxidative stress response [40][41][42]. Inhibition of FOXO1 can reduce the expression of TNF-α and IL-6 [43].…”

Section: Discussionmentioning

confidence: 99%

Integrated Network Pharmacology and Mice Model to Investigate Qing Zao Fang for Treating Sjögren’s Syndrome

Zeng

Liu

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Sjögren’s syndrome (SS) is an autoimmune disease, and its conventional treatment has exhibited limited therapeutic efficacy. Qing Zao Fang (QZF), a traditional Chinese medicine formula, is used in the treatment of Sjögren’s syndrome, but its chemical composition is complex, and its pharmacological mechanism is not clear. Therefore, this study aims to explore the potential mechanism of QZF in the treatment of Sjögren’s syndrome based on network pharmacology and SS mouse model. The main active components and predicted targets of QZF were analyzed by network pharmacology. The SS mouse model was constructed and divided into 6 groups: control, SS, SS + hydroxychloroquine (HCQ)-treated, SS + low-dose QZF-treated, SS + medium-dose QZF-treated, and SS + high-dose QZF-treated group. Immunohistochemical, ELISA, and qRT-PCR assays were performed to detect the expressions of targets associated with SS. TUNEL staining was used to detect apoptosis. Cumulatively, 230 active compounds and 1883 targets of QZF were identified. There were 227 common targets for QZF and SS. The effective active ingredients were stigmasterol, neocryptotanshinone II, neotanshinone C, miltionone I, and beta-pinene. It mainly acts on biological processes such as inflammatory response, chemokine metabolic process, and immune response as well as pathways such as FoxO signaling pathway, Yersinia infection, HIF-1 signaling pathway, and TNF signaling pathway. In SS mice, levels of AKT1, HIF-1α, TNF-α, IL-6, and IL-17A were increased, while decreased after QZF treatment. In contrast, IL-10 levels were decreased in SS mice and increased in QZF-treated mice. In addition, QZF reduced apoptosis in the submandibular gland tissue compared to SS mice. It can be concluded that the QZF in treatment of SS is the result of the combined action of multiple components, multiple targets, and multiple pathways. This study improves the understanding of the link between QZF and SS on molecular mechanisms.

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“…The miR-223-3p might be a therapeutic target for enhancing bone functions. By increasing autophagy via targeting FOXO3, downregulated miR-223-3p expression promoted osteogenic differentiation of BM-MSCs [25].…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Hub Genes and miRNAs in Osteoporosis

Huang

Zhao

et al. 2021

Preprint

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Background and objective: Osteoporosis (OP) is a systemic disease of bone metabolism, characterized by decreasing bone mass, increasing bone microstructure damages and fracture risk. It affects the quality of life of nearly 200 million people worldwide and is a major burden on the public health systems. We want to identify hub genes and miRNAs by the miRNA-mRNA interaction network in osteoporosis disease so that further understand the pathogenesis of this disease.Materials and methods: The differentially expressed miRNAs (DEMis) and mRNAs (DEMs) were selected using data of OP patients downloaded from the GEO database (GSE93883, GSE74209 and GSE35959). Gene Ontology (GO) pathway analysis and transcription factor enrichment analysis were used for selecting DEMis, and the target mRNAs of DEMis were filtered by using FunRich. Cytoscape software was used to visualize the network between miRNAs and mRNAs and calculate the hub genes. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the mRNAs in the regulatory network.Results: A total of 17 DEMis and 655 DEMs were selected, from which we reconstructed the miRNA-mRNA network consisting of 6 miRNAs and 37 mRNAs. The top 10 nodes, hsa-let-7a-5p, hsa-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-223-3p, hsa-miR-320c, SLC2A3(Solute Carrier Family 2 Member 3), LBX1(ladybird homeobox 1), HCN2(hyperpolarization-activated cyclic nucleotide-gated ion channel 2), DAB2IP(DAB2 Interacting Protein) and CIC(capicua transcriptional repressor), were identified as important regulators.Conclusions: The study uncovered several important hub genes and miRNAs involved in the pathogenesis of OP, among which, the hsa-let-7a-5p, hsa-miR-92a-3p and hsa-miR-92b-3p may play an important role in osteoporosis, which can help us provide potential therapeutic targets of OP.

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FOXO3 is targeted by miR-223-3p and promotes osteogenic differentiation of bone marrow mesenchymal stem cells by enhancing autophagy

Cited by 26 publications

References 34 publications

Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches

Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches

Integrated Network Pharmacology and Mice Model to Investigate Qing Zao Fang for Treating Sjögren’s Syndrome

Integrated Analysis of Hub Genes and miRNAs in Osteoporosis

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