LncRNA NEAT1 Sponges MiRNA-148a-3p to Suppress Choroidal Neovascularization and M2 macrophage polarization

Zhang, Pengfei; Lu, Bing; Zhang, Qi; Xu, Feng-Yuan; Zhang, Rongrong; Wang, Chen; Liu, Yinping; Wei, Chenghua; Mei, Lixin

doi:10.1016/j.molimm.2020.08.008

Cited by 28 publications

(20 citation statements)

References 15 publications

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“…A total of 7 miRNAs, including 5 AS is a lipid-driven inflammatory disease, and inflammation has long been considered a marker of AS. Recent studies have found that miR-148a-3p plays a critical role in inflammatory diseases (27)(28)(29) and angiogenesis (30,31). The knockdown of SULT2B1b has been shown to inhibit the inflammatory response via increasing the miR-148a-3p level in macrophages (32).…”

Section: Mir-148a-3p Attenuates Apoptosis and Inflammation By Targeti...mentioning

confidence: 99%

MiR-148a-3p attenuates apoptosis and inflammation by targeting CNTN4 in atherosclerosis

Wang¹,

Huang²,

Miao³

et al. 2022

Ann Transl Med

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Background: Atherosclerosis (AS) seriously affects human health. The role of microRNAs (miRNAs) in the pathogenesis and progression of AS has become a focus of research. Our goal was to identify the biological effect of differentially expressed miRNAs (DE-miRNAs) in AS. Methods:To analyze differentially expressed genes (DEGs), including differentially expressed mRNAs (DE-mRNAs) and DE-miRNAs, in AS by using the Gene Expression Omnibus (GEO) database and limma package. DEGs protein-protein interaction (PPI) network and functional enrichment analysis were constructed by using the search tool for the retrieval of interacting genes/proteins (STRING) database, Cytoscape software and Cytoscape plugin "ClueGO2.5.6". We established a coexpression network of dysregulated miRNAs and mRNAs to predict the function of miRNAs by using miRWalk database and Pearson correlation coefficient (PCC) analysis. Cellular experiments were used to validate the results of bioinformatics.Results: First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R. Next, a DEG PPI network was constructed. Functional enrichment analysis of DEGs showed that 11 functional pathways were significantly enriched, such as positive regulation of monocyte chemotaxis.Seven common DE-miRNAs were obtained from the GSE99685 dataset and DE-mRNAs predicted miRNAs through the miRWalk database. The miRNA-mRNA network constructed using Cytoscape software suggested that miR-148a-3p targeted contactin 4 (CNTN4). Quantitative real-time polymerase chain reaction (qRT-PCR) assay results indicated that miR-148a-3p was downregulated and CNTN4 was upregulated in the THP-1 + phorbol 12-myristate 13-acetate (PMA) + oxidized low-density lipoprotein (oxLDL) group compared with the THP-1 + PMA group. qRT-PCR, flow cytometry, and ELISA found that upregulated miR-148a-3p significantly inhibited the expression of CNTN4, cell apoptosis, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations in oxLDL-induced THP-1 macrophages. In addition, a dual-luciferase reporter assay demonstrated that CNTN4 was a target gene of miR-148a-3p.Conclusions: Overall, these findings suggested that miR-148a-3p inhibited oxLDL-induced cell apoptosis and inflammation via targeting CNTN4 in THP-1 macrophages.

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Section: Mir-148a-3p Attenuates Apoptosis and Inflammation By Targeti...mentioning

confidence: 99%

MiR-148a-3p attenuates apoptosis and inflammation by targeting CNTN4 in atherosclerosis

Wang¹,

Huang²,

Miao³

et al. 2022

Ann Transl Med

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“…Consistently, Zhang et al . found M2 polarization can be promoted by NEAT1 and promotes choroidal neovascularization by sponging miRNA-148a-3p [ 42 ]. Besides, NEAT1 accelerates multiple myeloma progression by regulating B7-H3 to promote M2 macrophage polarization [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal Lnc NEAT1 from endothelial cells promote bone regeneration by regulating macrophage polarization via DDX3X/NLRP3 axis

Chen

Guo

et al. 2023

J Nanobiotechnol

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Background Bone regeneration is a complex procedure that involves an interaction between osteogenesis and inflammation. Macrophages in the microenvironment are instrumental in bone metabolism. Amount evidence have revealed that exosomes transmitting lncRNA is crucial nanocarriers for cellular interactions in various biotic procedures, especially, osteogenesis. However, the underlying mechanisms of the regulatory relationship between the exosomes and macrophages are awaiting clarification. In the present time study, we aimed to explore the roles of human umbilical vein endothelial cells (HUVECs)-derived exosomes carrying nuclear enrichment enriched transcript 1 (NEAT1) in the osteogenesis mediated by M2 polarized macrophages and elucidate the underlying mechanisms. Results We demonstrated HUVECs-derived exosomes expressing NEAT1 significantly enhanced M2 polarization and attenuated LPS-induced inflammation in vitro. Besides, the conditioned medium from macrophages induced by the exosomes indirectly facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Mechanically, Exos carrying NEAT1 decreased remarkably both expression of dead-box helicase 3X-linked (DDX3X) and nod-like receptor protein 3 (NLRP3). The level of NLRP3 protein increased significantly after RAW264.7 cells transfected with DDX3X overexpression plasmid. Additionally, the knockdown of NEAT1 in exosomes partially counteracted the aforementioned effect of Exos. The results of air pouch rat model demonstrated that HUVECs-derived exosomes increased anti-inflammatory cytokines (IL-10) and decreased pro-inflammatory cytokines (IL-1β and IL-6) significantly in vivo, contributing to amelioration of LPS-induced inflammation. Afterwards, we further confirmed that the HUVECs-derived exosomes encapsulated in alginate/gelatin methacrylate (GelMA) interpenetrating polymer network (IPN) hydrogels could promote the bone regeneration, facilitate the angiogenesis, increase the infiltration of M2 polarized macrophages as well as decrease NLRP3 expression in the rat calvarial defect model. Conclusions HUVECs-derived exosomes enable transmitting NEAT1 to alleviate inflammation by inducing M2 polarization of macrophages through DDX3X/NLRP3 regulatory axis, which finally contributes to osteogenesis with the aid of alginate/GelMA IPN hydrogels in vivo. Thus, our study provides insights in bone healing with the aid of HUVECs-derived exosomes-encapsulated composite hydrogels, which exhibited potential towards the use of bone tissue engineering in the foreseeable future.

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“…A reduction in the protein level of signal transducer and activator of transcription 3 is also observed when NEAT1 is inhibited (21). Furthermore, lncRNA NEAT1 plays a role in regulating choroidal neovascularization and M2 macrophage polarization (22). Cancer cells from the endometrium and breast may also be significantly slowed by lncRNA NEAT1 (23,24).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of lncRNA NEAT1 inhibits the proliferation of human cutaneous squamous cell carcinoma in vivo and in vitro

Shen¹,

Huang²,

Zhang³

et al. 2022

Ann Transl Med

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Background: The incidence of cutaneous squamous cell carcinoma (CSCC), a malignant tumor that threatens human life, is increasing every year, and yet its pathogenesis is still unclear. This study found that long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) was abnormally expressed in CSCC. However, the biochemical mechanisms of lncRNA NEAT1 in carcinogenesis and the development of cancer remain unclear.Methods: Fluorescence quantitative polymerase chain reaction (qPCR) was conducted to determine lncRNA NEAT1 expression in CSCC and paracarcinoma tissues and investigate the correlation between NEAT1 levels and patients' clinicopathological features. The invasion, proliferation, and migration of CSCC cells were measured using colony formation, Cell Counting Kit-8, and Transwell assays. Western blot assay was conducted to test whether NEAT1 knockdown affected invasion and migration-related proteins. In addition, a nude mouse subcutaneous tumorigenesis experiment was performed to determine whether the knockdown of NEAT1 affected the proliferation ability of CSCC cells.Results: Changes in lncRNA NEAT1 expression in CSCC tissues were correlated with the degree of lymph node metastasis and the tumor, regional lymph nodes, and distant metastasis (TNM) grade of patients. The downregulation of NEAT1 lncRNA significantly impeded cell invasion, proliferation, and migration in CSCC. Through lncRNA NEAT1 knockdown, significant reductions in metalloproteinase-2, metalloproteinase-9, N-cadherin, and vimentin expression were observed, and the level of E-cadherin increased. In vivo experiments in nude mice revealed that knockdown of lncRNA NEAT1 greatly inhibited cell proliferation in CSCC. Conclusions:In CSCC tissues, NEAT1 lncRNA was expressed at high levels and correlated with lymph node metastasis and TNM stage. The knockdown of NEAT1 lncRNA could significantly impede CSCC proliferation, metastasis, and invasion. Additionally, by measuring the expression level of lncRNA NEAT1, we may be able to detect the clinical and pathological characteristics of CSCC.

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LncRNA NEAT1 Sponges MiRNA-148a-3p to Suppress Choroidal Neovascularization and M2 macrophage polarization

Cited by 28 publications

References 15 publications

MiR-148a-3p attenuates apoptosis and inflammation by targeting CNTN4 in atherosclerosis

MiR-148a-3p attenuates apoptosis and inflammation by targeting CNTN4 in atherosclerosis

Exosomal Lnc NEAT1 from endothelial cells promote bone regeneration by regulating macrophage polarization via DDX3X/NLRP3 axis

Downregulation of lncRNA NEAT1 inhibits the proliferation of human cutaneous squamous cell carcinoma in vivo and in vitro

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