Cobalt chloride-stimulated hypoxia promotes the proliferation of cholesteatoma keratinocytes via the PI3K/Akt signaling pathway

Zhang, Chen; Chen, Min; Qi, Tao; Chi, Zhangcai

doi:10.7150/ijms.60617

Cited by 8 publications

(9 citation statements)

References 25 publications

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“…Protein kinase B signaling plays a crucial role in cell growth, differentiation, and survival (Cantley, 2002). HIF‐1 consists of HIF‐1α and HIF‐1β, and HIF‐1α activity is regulated through the PI3K/Akt pathway (Zhang et al, 2021). Interestingly, PCOS is characterized by in vivo dysregulated hormone secretion and metabolic disorders (Carmina et al, 2010; Norman et al, 2007; Rotterdam ESHRE/ASRM‐Sponsored PCOS Consensus Workshop Group, 2004).…”

Section: Resultsmentioning

confidence: 99%

Investigating the active components of Huatan Tongjing decoction for the treatment of polycystic ovary syndrome via network pharmacology

Zeng

et al. 2022

Chem Biol Drug Des

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Section: Resultsmentioning

confidence: 99%

Investigating the active components of Huatan Tongjing decoction for the treatment of polycystic ovary syndrome via network pharmacology

Zeng

et al. 2022

Chem Biol Drug Des

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“…Recently, cholesteatoma has been recognized as hypoxic tissue resulting from under-aeration of the middle ear cleft in most cases. 16,22 In fact, it has become evidence that hypoxia represents one of the major contributing factors in the development and progression of cholesteatoma. 4 Herein, our findings provided evidence that HIF1A, as a key element in hypoxia response, is highly expressed in human cholesteatoma samples, consistent with a previous study.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, cholesteatoma has been recognized as hypoxic tissue resulting from under‐aeration of the middle ear cleft in most cases 16,22 . In fact, it has become evidence that hypoxia represents one of the major contributing factors in the development and progression of cholesteatoma 4 .…”

Section: Discussionmentioning

confidence: 99%

“…Lately, recent literature has suggested that the overexpression of HIF1A might promote cholesteatoma deterioration and bone erosion 15 . Beyond that, dysregulated HIF1A was previously validated to be closely associated with the proliferation of cholesteatoma keratinocytes 16 . Nevertheless, current studies on the expression and underlying mechanism of HIF1A in cholesteatoma keratinocyte proliferation are far from being addressed.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia‐inducible factor‐1α contributes to the proliferation of cholesteatoma keratinocytes through regulating endothelin converting enzyme 1 expression

Chen,

Xu,

et al. 2024

Laryngoscope Investig Oto

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ObjectiveCholesteatoma is a hyperproliferative, pseudoneoplastic lesion of the middle ear characterized by aggressive growth and bone destruction. Hypoxia‐inducible factor‐1α (HIF‐1α, also known as HIF1A) is a key transcription factor that enters the nucleus and upregulates many genes involved in cancer progression in the oxygen‐free environment. This study is designed to explore the role and mechanism of HIF1A in the progression of cholesteatoma.MethodsHIF1A and endothelin converting enzyme 1 (ECE1) levels were determined using real‐time quantitative polymerase chain reaction. The protein levels of HIF1A, Cyclin D1, proliferating cell nuclear antigen, and ECE1 were measured using western blot. Cell viability, proliferation, and cell cycle progression were analyzed using cell counting kit‐8, Colony formation, 5‐ethynyl‐2′‐deoxyuridine, and flow cytometry assays. Binding between HIF‐1α and ECE1 promoter was predicted by Jaspar and verified using Chromatin immunoprecipitation and dual‐luciferase reporter assays.ResultsHIF1A and ECE1 were highly expressed in cholesteatoma patients and keratinocytes. Moreover, HIF1A knockdown might suppress the cell viability, proliferation, and cycle progression of cholesteatoma keratinocytes. Furthermore, HIF1A upregulated the transcription of ECE1 through binding to its promoter region.ConclusionHIF1A might expedite cholesteatoma keratinocyte proliferation partly by increasing ECE1 expression, providing a possible therapeutic target for the cholesteatoma treatment.

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“…Since hypoxia is common in MEC tissue, the expression of hypoxia-inducible factor 1 (HIF-1) was significantly increased in MEC compared to normal skin [ 90 ] and localized to keratinocytes located on the basal layer [ 91 ]. Interestingly, the likelihood of relapse after surgery was correlated to HIF-1 expression [ 90 ].…”

Section: Applicable Targets In Precision Medicine For Mec Therapymentioning

confidence: 99%

Review of potential medical treatments for middle ear cholesteatoma

2022

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Middle ear cholesteatoma (MEC), is a destructive, and locally invasive lesion in the middle ear driven by inflammation with an annual incidence of 10 per 100,000. Surgical extraction/excision remains the only treatment strategy available and recurrence is high (up to 40%), therefore developing the first pharmaceutical treatments for MEC is desperately required. This review was targeted at connecting the dysregulated inflammatory network of MEC to pathogenesis and identification of pharmaceutical targets. We summarized the numerous basic research endeavors undertaken over the last 30+ years to identify the key targets in the dysregulated inflammatory pathways and judged the level of evidence for a given target if it was generated by in vitro, in vivo or clinical experiments. MEC pathogenesis was found to be connected to cytokines characteristic for Th1, Th17 and M1 cells. In addition, we found that the inflammation created damage associated molecular patterns (DAMPs), which further promoted inflammation. Similar positive feedback loops have already been described for other Th1/Th17 driven inflammatory diseases (arthritis, Crohn’s disease or multiple sclerosis). A wide-ranging search for molecular targeted therapies (MTT) led to the discovery of over a hundred clinically approved drugs already applied in precision medicine. Based on exclusion criteria designed to enable fast translation as well as efficacy, we condensed the numerous MTTs down to 13 top drugs. The review should serve as groundwork for the primary goal, which is to provide potential pharmaceutical therapies to MEC patients for the first time in history.

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Cobalt chloride-stimulated hypoxia promotes the proliferation of cholesteatoma keratinocytes via the PI3K/Akt signaling pathway

Cited by 8 publications

References 25 publications

Investigating the active components of Huatan Tongjing decoction for the treatment of polycystic ovary syndrome via network pharmacology

Investigating the active components of Huatan Tongjing decoction for the treatment of polycystic ovary syndrome via network pharmacology

Hypoxia‐inducible factor‐1α contributes to the proliferation of cholesteatoma keratinocytes through regulating endothelin converting enzyme 1 expression

Review of potential medical treatments for middle ear cholesteatoma

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