miR-210 regulates the inflammation of otitis media with effusion by inhibiting the expression of hypoxia-inducible factor (HIF)-1a

Zhang, jintang; He, Jian‐Guo; Luo, yamei; Liu, yatian; Fan, Xiaofan

doi:10.1016/j.bbrc.2020.11.068

Cited by 9 publications

(15 citation statements)

References 29 publications

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“…Of note, the transfection of HMEEcs with miR-210 mimics led to a significant reduction in the expression levels of pro-inflammatory cytokines and cell apoptosis, whereas cell viability was increased. In addition, miR-210 overexpression was also related to the downregulation of hypoxia-inducible factor-1α, a transcriptional factor involved in pro-inflammatory gene expression (83). Overall, the obtained results suggested that miR-210 overexpression may represent the starting point for a novel therapeutic approach with which to reduce ear inflammatory processes.…”

Section: Involvement Of Mirnas In Ear Infection and Inflammatory Proc...mentioning

confidence: 73%

“…Recently, the role of miR-210 in otitis media was also investigated. Specifically, Zhang et al (83) observed that miR-210 levels were significantly downregulated in middle ear effusion in the serum of patients affected by otitis media. On the contrary, the expression levels of pro-inflammatory cytokines, as well as nitric oxide and vascular endothelial growth factor (VEgF) were increased in the otitis group compared to the controls (83).…”

Section: Involvement Of Mirnas In Ear Infection and Inflammatory Proc...mentioning

confidence: 99%

“…Specifically, Zhang et al (83) observed that miR-210 levels were significantly downregulated in middle ear effusion in the serum of patients affected by otitis media. On the contrary, the expression levels of pro-inflammatory cytokines, as well as nitric oxide and vascular endothelial growth factor (VEgF) were increased in the otitis group compared to the controls (83). These authors then conducted a functional assay to evaluate the potential regulatory role of the aforementioned miRNA.…”

Section: Involvement Of Mirnas In Ear Infection and Inflammatory Proc...mentioning

confidence: 99%

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Role of microRNAs as novel diagnostic biomarkers and potential therapeutic targets for hearing disorders (Review)

et al. 2022

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The ear is a complex structure consisting of the outer, middle and inner ear. For the proper function of the auditory system, the development of all these parts needs to be highly organized. Any alterations in this chain of events can lead to hearing loss or other impairments, such as dizziness, tinnitus and loss of balance. Of note, several external and internal elements, including noise exposure, ototoxic drugs, aging, as well as environmental or genetic factors, have been widely associated with hearing loss. Over the years, a growing body of evidence has indicated that microRNAs (miRNAs/miRs) play a critical role in ear development and auditory function, suggesting that an altered pattern of miRNA expression may be involved in the progression of these pathological conditions. On these bases, the present review article aimed to summarize the role of miRNAs in inner ear development and hearing disorders. Although further studies are warranted to provide more in-depth knowledge of the implicated mechanisms of action, according to the current data, miRNAs may be used as novel diagnostic biomarkers for the early detection of hearing loss. In addition, miRNAs and related signaling pathways may represent novel potential therapeutic targets for the treatment of hearing loss, ear inflammation and vestibular schwannoma.

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Section: Involvement Of Mirnas In Ear Infection and Inflammatory Proc...mentioning

confidence: 73%

Section: Involvement Of Mirnas In Ear Infection and Inflammatory Proc...mentioning

confidence: 99%

Section: Involvement Of Mirnas In Ear Infection and Inflammatory Proc...mentioning

confidence: 99%

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Role of microRNAs as novel diagnostic biomarkers and potential therapeutic targets for hearing disorders (Review)

et al. 2022

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“…HMEECs were purchased from Cell Bank of Chinese Academy of Sciences (Shanghai, China) and cultured in 50/50 mixture of DMEM and BEBM (both from Gibco) at 37°C with 5% CO 2 . To construct an in vitro OME model, 100 ng/ml lipopolysaccharide (LPS) was used to treat HMEEC cells as previously described [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) promotes the inflammation and apoptosis of otitis media with effusion through targeting microRNA (miR)-495 and activation of p38 MAPK signaling pathway

Dong

Huang

et al. 2021

Bioengineered

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Long non-coding RNA (lncRNA) plays a vital role in human inflammatory diseases. Our study aimed to investigate the function of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in otitis media with effusion (OME). The mRNA levels of NEAT1 and miR-495 were measured by RT-qPCR. The protein levels of p38 MAPK were detected by western blot. The levels of inflammatory cytokines were examined by ELISA. CCK-8 and flow cytometry assays were used to evaluate the cell viability and apoptosis, respectively. The interaction between NEAT1 and miR-495 was determined by luciferase reporter and RIP assays. NEAT1 was highly expressed in OME, and silencing of NEAT1 facilitated the cell proliferation and suppressed levels of inflammatory cytokines and cell apoptosis in LPS-induced HMEECs. Moreover, miR-495 was confirmed as a downstream target of NEAT1. Functional assays revealed that NEAT1 promoted the OME by targeting miR-495. It was further demonstrated that NEAT1 could activate the p38 MAPK signaling pathway by regulating miR-495, and the p38 MAPK inhibitor restored the effects of NEAT1 overexpression on the inflammation levels, cell proliferation, and apoptosis. Our study revealed that lncRNA NEAT1 served as a ceRNA to activate p38 MAPK signaling by targeting miR-495 in OME, which may offer a new target for OME treatment.

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“…HIF-1 plays an important role in embryonic angiogenesis, tumor angiogenesis, and pathophysiology of ischemic diseases. For example, it has been reported that HIF-1α promotes tumor chemotherapy resistance by recruiting GDF15induced tumor-associated macrophages in colorectal cancer [6]; silencing long noncoding RNA NEAT1 stimulates HIF-1α/NF-kappaB by competitively binding miR-33a-5p to inhibit the occurrence of infantile hemangioma [7]; under hypoxic conditions, miR-375 impairs the invasion ability of liver cancer cells through targeted regulation of HIF-1α [8]; in the process of IL-1β-induced chondrocyte degeneration, FBW7 regulates the HIF-1α/VEGF pathway [9]; miR-210 regulates the inflammatory response of exudative otitis media by inhibiting the expression of HIF-1α [10]; extracellular vesicles from healthy cells activate and improve the cell function of progeria stem cells and stem cells themselves through miR-302b and HIF-1α [11].…”

Section: Introductionmentioning

confidence: 99%

Study on the Mechanism of Capillary Leakage Caused by Hypoxia-Inducible Factor-1α through Inducing High Expression of Matrix Metalloproteinase-9

Li¹,

Huang²,

Cui³

et al. 2021

Journal of Oncology

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Purposes. This study mainly explored the mechanism of capillary leakage caused by hypoxia-inducible factor-1α through inducing high expression of matrix metalloproteinase-9. Method. We established a monolayer endothelial cell model by culturing human umbilical vein endothelial cells (HUVEC) in vitro, used tumor necrosis factor (TNFα) and HIF-1α inhibitor 2-methoxyestradiol (2ME2) to act on HUVEC, and at the same time constructed siRNA-transfected HUVEC to interfere with the expression of HIF-1α. The permeability of monolayer endothelial cells was measured by transwell chamber method, the concentration of MMP-9 in the supernatant was measured by ELISA method, the expression of key molecules related to permeability (HIF- 1α, MMP-9, claudin-5, and ZO-1) was measured by RT-PCR and Western blot method, and the localization and expression of claudin-5 and ZO-1 were measured by immunofluorescence method. We searched for 7 HIF-1α hypoxia response elements within 4000 bp before the transcription start site in the MMP-9 promoter region, constructed the MMP-9 promoter-luciferase reporter gene recombinant plasmid, transfected and stimulated HUVEC with TNFα, and detected the effect of 7 hypoxia response element plasmids on the transcription activity of MMP-9 promoter. Results. Under the action of TNFα, the permeability of monolayer endothelial cells increased, and the concentration of MMP-9 in the cell supernatant increased. 2ME2 and HIF-1α-siRNA transfection can improve the above situation ( P < 0.05 ). 2ME2 and HIF-1α-siRNA transfection can inhibit the high expression of HIF-1α and MMP-9 caused by TNFα, thereby increasing the expression of claudin-5 and ZO-1 ( P < 0.05 ). 2ME2 and HIF-1α-siRNA transfection can reduce the inhibition of TNFα on the expression of cell membrane protein claudin-5 and tight junction protein ZO-1. Element 1, element 5, and element 7 are the sites where HIF-1α interacts with MMP-9 at the transcription level. Conclusion. This study shows that HIF-1α can increase the permeability of monolayer epithelial cells by inducing the high expression of MMP-9, leading to capillary leakage. Its target is at the −3798 bp, −1878 bp, and −1489 bp points of the transcription initiation site in the MMP-9 promoter region.

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miR-210 regulates the inflammation of otitis media with effusion by inhibiting the expression of hypoxia-inducible factor (HIF)-1a

Cited by 9 publications

References 29 publications

Role of microRNAs as novel diagnostic biomarkers and potential therapeutic targets for hearing disorders (Review)

Role of microRNAs as novel diagnostic biomarkers and potential therapeutic targets for hearing disorders (Review)

Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) promotes the inflammation and apoptosis of otitis media with effusion through targeting microRNA (miR)-495 and activation of p38 MAPK signaling pathway

Study on the Mechanism of Capillary Leakage Caused by Hypoxia-Inducible Factor-1α through Inducing High Expression of Matrix Metalloproteinase-9

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