Novel and recurrent keratin 6A (<i>KRT6A</i>) mutations in Chinese patients with pachyonychia congenita type 1

Lv, Yong Mei; Yang, Sen; Zhang, Z.; Cui, Yifan; Cheng, Qimin; Zhou, Fusheng; Fang, Qiaoyun; Du, Wenhui; Zhang, F.R.; Chang, Jinlong; Tao, Xiaoyong; Zhang, A.L.; Kang, Ran; Du, Wei‐Dong; Zhang, X.J.

doi:10.1111/j.1365-2133.2009.09062.x

Cited by 3 publications

(4 citation statements)

References 8 publications

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“…18 Keratin type II cytoskeletal 6A, together with 16A, is associated with epidermal hyperproliferation. 19 Pachyonychia congenita typically presents with nail hyperkeratosis, and our previous study confirmed that pachyonychia congenita type 1 is significantly associated with keratin 6A (KRT6A) mutations in Chinese patients. 19 As a benign tumour, the physiopathologic mechanism of VEN is similar to that of malignant tumours in terms of cell invasion and metastasis.…”

Section: Discussionsupporting

confidence: 62%

“…In addition, keratins, also called cytokeratins, are intermediate filament proteins that create an insoluble dense meshwork through the cytoplasm, associated with many benign skin tumours, such as steatocystoma multiplex, hidradenoma and papillary eccrine adenoma 18 . Keratin type II cytoskeletal 6A, together with 16A, is associated with epidermal hyperproliferation 19 . Pachyonychia congenita typically presents with nail hyperkeratosis, and our previous study confirmed that pachyonychia congenita type 1 is significantly associated with keratin 6A (KRT6A) mutations in Chinese patients 19 .…”

Section: Discussionmentioning

confidence: 99%

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Differentially expressed proteins identified by TMT proteomics analysis in children with verrucous epidermal naevi

Yuan

Cai

Sheng

et al. 2021

Acad Dermatol Venereol

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Background Verrucous epidermal naevi (VEN) are benign skin tumours, considered keratinocytic epidermal naevi, that appear at birth or early childhood. VEN may display a range of appearances, depending on patient age. Although the number of studies regarding VEN is increasing, the exact mechanism of VEN is still unknown.Objectives The aim of this study was to analyse the changes in the expression of protein factors in lesions of VEN children by TMT labelling-based quantitative proteomics.Methods A total of 8 children with VEN (5 for experiment and 3 for validation) and 8 healthy children (5 for experiment and 3 for validation) presented to the Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Boao Super Hospital, between January 2019 and November 2019. The lesions and lesion-adjacent tissues from children with VEN and naevus-adjacent normal skin tissues from children with pigmented naevi were defined as the VEN group, VENC group and C group, respectively. We performed a proteomics analysis to screen for differentially expressed proteins in the lesions of these individuals. We further performed Western blotting to validate the relative expression levels of nine targeted proteins in the validation group.Results According to the proteomics results, a total of 4970 proteins were identified, and 4770 proteins were quantified. Among these proteins, 586 proteins were up-or downregulated at least 1.3-fold with a P-value < 0.05 (upregulated: 399, downregulated: 187) in lesions between the VEN group and the C group. These proteins played important roles in multiple biological functions, such as cornification, epidermal cell differentiation and neutrophil activation, and formed a complicated protein-protein interaction network. Of the 586 up-or downregulated proteins, nine were selected for further validation. According to Western blotting analysis results, the relative expression levels of Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A (Cytokeratin 6A), BRAF, Filaggrin, S100A7 and Desmocollin-3 were significantly upregulated in VEN children and may be associated with skin barrier dysfunction, epidermal cell overgrowth and differentiation, inflammation and immune and oxidative phosphorylation, which are involved in the pathogenesis of VEN.Conclusions According to TMT-based proteomics and Western blotting results, we identified eight noteworthy proteins, Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A, BRAF, Filaggrin, S100A7 and Desmocollin-3, that were upregulated in the lesions of VEN children and may be associated with the pathogenesis of VEN. Our findings provide new starting points for identifying precise pathogenic mechanisms or therapeutic targets for VEN.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Differentially expressed proteins identified by TMT proteomics analysis in children with verrucous epidermal naevi

Yuan

Cai

Sheng

et al. 2021

Acad Dermatol Venereol

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“…KRT6A are a member of type II epithelial keratins, which are intermediate filament-forming proteins that provide mechanical support and fulfil a variety of additional functions in epithelial cells. The presence of KRT6A was associated with pachyonychia congenital [44], as well as renal carcinoma [45] and breast cancer progression [46]. Genome-wide expression profiling with linkage analysis revealed that the transcription level of KRT6A significantly increased in peripheral blood mononuclear cells (PBMCs), airway brushing cells (ABCs), and bronchioalveolar lavage (BAL) when asthmatics were exposed to cockroach allergen [47].…”

Section: Resultsmentioning

confidence: 99%

Consistent Biomarkers and Related Pathogenesis Underlying Asthma Revealed by Systems Biology Approach

Nie

Wei

Hao

et al. 2019

IJMS

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Asthma is a common chronic airway disease worldwide. Due to its clinical and genetic heterogeneity, the cellular and molecular processes in asthma are highly complex and relatively unknown. To discover novel biomarkers and the molecular mechanisms underlying asthma, several studies have been conducted by focusing on gene expression patterns in epithelium through microarray analysis. However, few robust specific biomarkers were identified and some inconsistent results were observed. Therefore, it is imperative to conduct a robust analysis to solve these problems. Herein, an integrated gene expression analysis of ten independent, publicly available microarray data of bronchial epithelial cells from 348 asthmatic patients and 208 healthy controls was performed. As a result, 78 up- and 75 down-regulated genes were identified in bronchial epithelium of asthmatics. Comprehensive functional enrichment and pathway analysis revealed that response to chemical stimulus, extracellular region, pathways in cancer, and arachidonic acid metabolism were the four most significantly enriched terms. In the protein-protein interaction network, three main communities associated with cytoskeleton, response to lipid, and regulation of response to stimulus were established, and the most highly ranked 6 hub genes (up-regulated CD44, KRT6A, CEACAM5, SERPINB2, and down-regulated LTF and MUC5B) were identified and should be considered as new biomarkers. Pathway cross-talk analysis highlights that signaling pathways mediated by IL-4/13 and transcription factor HIF-1α and FOXA1 play crucial roles in the pathogenesis of asthma. Interestingly, three chemicals, polyphenol catechin, antibiotic lomefloxacin, and natural alkaloid boldine, were predicted and may be potential drugs for asthma treatment. Taken together, our findings shed new light on the common molecular pathogenesis mechanisms of asthma and provide theoretical support for further clinical therapeutic studies.

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“…Both KRT6A and KRT6B are type II cytokeratins and keratin 6 isoforms [ 52 , 53 ]. KRT6A and KRT6B are associated with pachyonychia congenita [ 54 , 55 ], as well as renal carcinoma [ 32 ] and breast cancer [ 56 ] progression. SFTA3 is an immunoregulatory protein that protects lung tissue during inflammation and is likely a lung surfactant protein family member [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma

Xiao

Chen

et al. 2017

Oncotarget

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Lung adenocarcinoma (LADC) and squamous cell carcinoma (LSCC) are the most common non-small cell lung cancer histological phenotypes. Accurate diagnosis distinguishing between these two lung cancer types has clinical significance. For this study, we analyzed four Gene Expression Omnibus (GEO) datasets (GSE28571, GSE37745, GSE43580, and GSE50081). We then imported the datasets into the Gene-Cloud of Biotechnology Information online platform to identify genes differentially expressed in LADC and LSCC. We identified DSG3 (desmoglein 3), KRT5 (keratin 5), KRT6A (keratin 6A), KRT6B (keratin 6B), NKX2-1 (NK2 homeobox 1), SFTA2 (surfactant associated 2), SFTA3 (surfactant associated 3), and TMC5 (transmembrane channel-like 5) as potential biomarkers for distinguishing between LADC and LSCC. Receiver operating characteristic curve analysis suggested that KRT5 had the highest diagnostic value for discriminating between these two cancer types. Using the PrognoScan online survival analysis tool and the Kaplan-Meier Plotter, we found that high KRT6A or KRT6B levels, or low NKX2-1, SFTA3, or TMC5 levels correlated with unfavorable prognoses in LADC patients. Further studies will be needed to verify our findings in additional patient samples, and to elucidate the mechanisms of action of these potential biomarkers in non-small cell lung cancer.

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Novel and recurrent keratin 6A (KRT6A) mutations in Chinese patients with pachyonychia congenita type 1

Abstract: Novel and recurrent KRT6A mutations, Y. M. LV et al. 1329

Cited by 3 publications

References 8 publications

Differentially expressed proteins identified by TMT proteomics analysis in children with verrucous epidermal naevi

Differentially expressed proteins identified by TMT proteomics analysis in children with verrucous epidermal naevi

Consistent Biomarkers and Related Pathogenesis Underlying Asthma Revealed by Systems Biology Approach

Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma

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