MiR-142-5p directly targets cyclin-dependent kinase 5-mediated upregulation of the inflammatory process in acquired middle ear cholesteatoma

Sui, Rongcui; Shi, Wei; Han, Shuhui; Fan, Xintai; Zhang, Xianzhao; Wang, Na; Zhang, Hao; Xu, Anting; Liu, Chengcheng

doi:10.1016/j.molimm.2021.11.017

Cited by 6 publications

(11 citation statements)

References 54 publications

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“…The miR-142b gene has the same sequence as miR-142-5p and miR-142-5p has been studied by our laboratory as a miRNA playing a crucial role in acquired middle ear cholesteatoma. 32 Therefore, miR-142-5p is the subject of subsequent analysis. First, by using RT-qPCR, it was found that the expression level of miR-142-5p in exosomes from AR group was significantly lower than that in the control WT group ( Figure 5B ).…”

Section: Resultsmentioning

confidence: 99%

“…Our previous study of miR-142-5p indicated that miR-142-5p plays a crucial role in acquired middle ear cholesteatoma (AMEC) via CDK5. 32 CDK5 is a serine/threonine protein kinase known to play an important role in cell division and transcription regulation through phosphorylation of transcriptional regulators TrkB, NUDEL, and STAT3. 33–35 In one report, CDK5-STAT3 pathway is activated in response to sciatic nerve injury and participates in axon regeneration upon peripheral nerve injury.…”

Section: Discussionmentioning

confidence: 99%

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Tfh Exosomes Derived from Allergic Rhinitis Promote DC Maturation Through miR-142-5p/CDK5/STAT3 Pathway

Teng¹,

Zhou²,

Xu³

et al. 2022

JIR

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Background Dendritic cells (DCs) play an important role in allergen signal presentation. Many studies showed that follicular helper T cells (Tfhs) are related to allergic rhinitis (AR). However, the relationship between Tfhs and DCs and the mechanism of their interaction with AR remain unclear. Purpose To explore the mechanism of Tfhs on DC maturation in AR. Methods Tfhs were isolated from OVA-sensitized mice and co-cultured with DCs derived from mouse bone marrow. DCs maturity was monitored using flow cytometry and immunofluorescence staining. Exosomes of Tfhs were extracted, and miRNAs inside exosomes were analyzed using RNA-seq to identify differentially expressed genes. Using the TargetScan algorithm, it was predicted that CDK5 is a direct target gene, which is validated in a dual luciferase assay. DCs were treated with miR-142-5p mimics or inhibitors or transfected with CDK5 small interfering RNAs to verify the regulatory effects of miR-142-5p and CDK5 on DC maturation. How CDK5 regulates STAT3 signaling pathway was investigated to elucidate the molecular mechanism of DC maturation. Finally, in an in vivo experiment, the exosomes of AR-derived Tfhs were injected intravenously to detect their promotion of AR. Results Tfh exosomes derived from AR mice contributed to DC maturation. RNA-seq results showed that miR-142-5p was the differentially decreased gene. Using the TargetScan algorithm, it was predicted that CDK5 was the target gene for the direct action of miR-142-5p. By detecting the effects of changes in the expression levels of miR-142-5p and CDK5 on DC maturation, it was demonstrated that miR-142-5p inhibits DC maturation by inhibiting CDK5 expression. CDK5-regulated STAT3 signaling pathway during DC maturation, and inhibition of the STAT3 signaling pathway can reverse the regulation of miR-142-5p/CDK5 on DC maturation. Finally, in vivo experiment indicated that the injection of AR-derived Tfhs promoted AR in mice. Conclusion Tfh-derived exosomes induce DC maturation by regulating miR-142-5p/CDK5/STAT3 signaling pathway, thereby promoting the occurrence of AR.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tfh Exosomes Derived from Allergic Rhinitis Promote DC Maturation Through miR-142-5p/CDK5/STAT3 Pathway

Teng¹,

Zhou²,

Xu³

et al. 2022

JIR

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“…A study by Sui et al confirmed the negative correlation between miR-142-5p and cyclin-dependent kinase 5 (CDK5) in terms of expression and regulation [ 32 ]. CDK5 was previously reported to contribute to increasing inflammatory responses [ 69 , 70 ].…”

Section: Literature Reviewmentioning

confidence: 99%

“…CDK5 was previously reported to contribute to increasing inflammatory responses [ 69 , 70 ]. Sui et al observed CDK5 overexpression in cholesteatoma tissue samples, which was found to be positively correlated with levels of the cytokines TNF-α, TGF-β1, IL-5, IL-6, and IL-17A [ 32 ]. It is commonly known that TNF-α, IL-6, and IL-17A affect the development and proliferation of epidermal cells [ 71 ].…”

Section: Literature Reviewmentioning

confidence: 99%

“…It is commonly known that TNF-α, IL-6, and IL-17A affect the development and proliferation of epidermal cells [ 71 ]. Therefore, it was suspected that the formation of a specific inflammatory microenvironment in cholesteatoma may result from the upregulation of IL-5 in AMEC [ 32 ]. Moreover, Sui et al hypothesized that the CDK5/MAPK/NF-κB pathway is used by miR-142-5p to regulate the secretion of inflammatory cytokines [ 32 ].…”

Section: Literature Reviewmentioning

confidence: 99%

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Micro RNAs and Circular RNAs in Different Forms of Otitis Media

Kotowski

Adamczyk

Szydłowski

2023

IJMS

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The aim of this comprehensive review was to present the current knowledge on the role of microRNAs (miRNAs) in acute, recurrent, and chronic forms of otitis media. Special attention was focused on cholesteatoma of the middle ear. MicroRNAs modulate gene expression, which, in turn, influences the development and likelihood of the recurrence of acute and aggressive chronic middle ear inflammatory processes. Moreover, this study discusses the modulating role of a specific subgroup of noncoding RNA, circular RNA (circRNA). Recognizing the precise potential pathways and the mechanisms of their function may contribute to a better understanding of the molecular bases of middle ear diseases and identifying novel methods for treating this demanding pathology. Articles published between 2009 and 2022 were used in this analysis. In this review, we provide a complete overview of the latest progress in identifying the role and mechanisms of particular miRNAs and circRNAs in acute, recurrent and chronic forms of otitis media.

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The Science of Cholesteatoma

Patel,

Welch

2024

Otolaryngologic Clinics of North America

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MiR-142-5p directly targets cyclin-dependent kinase 5-mediated upregulation of the inflammatory process in acquired middle ear cholesteatoma

Cited by 6 publications

References 54 publications

Tfh Exosomes Derived from Allergic Rhinitis Promote DC Maturation Through miR-142-5p/CDK5/STAT3 Pathway

Tfh Exosomes Derived from Allergic Rhinitis Promote DC Maturation Through miR-142-5p/CDK5/STAT3 Pathway

Micro RNAs and Circular RNAs in Different Forms of Otitis Media

The Science of Cholesteatoma

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