Characterization of Tumor Suppressive Function of cornulin in Esophageal Squamous Cell Carcinoma

Chen, Kai; Li, Yan; Dai, Yongdong; Li, Jiangchao; Qin, Yanru; Zhu, Ying–Hui; Zeng, Tingting; Ban, Xiaohua; Fu, Li; Guan, Xin Yuan

doi:10.1371/journal.pone.0068838

Cited by 64 publications

(36 citation statements)

References 40 publications

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“…To resolve the question if the CRNN mRNA reduction in AD skin is caused by a gene polymorphism or whether other factors are involved, as is the case with FLG , whose expression is diminished by Th2 cytokines [1,17] , further studies are necessary. The reduction of CRNN mRNA and protein levels was previously reported in primary esophageal squamous cell carcinoma (SCC) and indicat-ed as an independent prognostic factor for esophageal SCC [36] . Furthermore, in laryngeal SCC, the CRNN transcript is downregulated [37] .…”

Section: Discussionmentioning

confidence: 82%

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Altered Expression of Genes Encoding Cornulin and Repetin in Atopic Dermatitis

Trzeciak¹,

Sakowicz-Burkiewicz

Wesserling

et al. 2017

Int Arch Allergy Immunol

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Background: It is assumed that beside alterations in the filaggrin gene (FLG), disturbances within genes encoding other cornified envelope proteins are also involved in atopic dermatitis (AD). To identify new potential markers of AD, we studied the polymorphisms of genes encoding repetin (RPTN), cornulin (CRNN), and their expression in the skin of AD patients. Methods: Polymorphisms in CRNN (rs941934), RPTN (rs284544, rs28441202, rs3001978, and rs12117644), and FLG mutations (R2447X, S3247X) were analyzed by TaqMan genotyping assay and by PCR-RFLP in the blood samples of 159 AD patients and 108 healthy subjects. The expression levels of CRNN and RPTN were determined by qRT-PCR in 34 AD skin samples (17 lesional and 17 nonlesional) and in 27 skin biopsies from healthy volunteers. The AD patients were recruited from the clinic of the university hospital between 2012 and 2014. Results:CRNN rs941934 (A allele) was associated with AD (OR 2.095, p = 0.008), a severe course of disease (p = 0.041), elevated IgE levels (p = 0.047), eosinophilia (p = 0.018), and concomitant asthma (p = 0.004). The mRNA level of CRNN was decreased in the AD skin (p = 0.041). In the AD patients without FLG mutations, the CC genotype of RPTN rs3001978 was associated with AD (OR 0.39, p = 0.037), early age at onset (p = 0.033), pruritus (p = 0.021), severity of AD (p = 0.045), and concomitant asthma (p = 0.041). The elevated mRNA levels of RPTN in lesional (p < 0.001) and nonlesional (p = 0.017) AD skin were observed. Conclusions: The single-nucleotide polymorphisms of CRNN (rs941934) and RPTN (rs3001978, rs28441202) may contribute to AD development, but further studies on a larger group of AD patients are needed to verify this assumption.

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Section: Discussionmentioning

confidence: 82%

“…Furthermore, in laryngeal SCC, the CRNN transcript is downregulated [37] . It has been demonstrated that CRNN is a tumor-suppressor gene [36] . On the other hand, there are studies reporting an increased risk of SCC among AD patients [38,39] .…”

Section: Discussionmentioning

confidence: 99%

Altered Expression of Genes Encoding Cornulin and Repetin in Atopic Dermatitis

Trzeciak¹,

Sakowicz-Burkiewicz

Wesserling

et al. 2017

Int Arch Allergy Immunol

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“…In a recent study by Chen et al it was shown that cornulin is a potential tumor suppressor and it regulates cell cycle progression at G1/S checkpoint by upregulating P21 WAF1/CIP1 and Rb. Thus it exerts its tumor suppressor effect by inhibiting G1 to S phase transition in cell cycle [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Downregulation of S100 Calcium Binding Protein A9 in Esophageal Squamous Cell Carcinoma

Pawar

Srikanth

Kashyap

et al. 2015

The Scientific World Journal

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The development of esophageal squamous cell carcinoma (ESCC) is poorly understood and the major regulatory molecules involved in the process of tumorigenesis have not yet been identified. We had previously employed a quantitative proteomic approach to identify differentially expressed proteins in ESCC tumors. A total of 238 differentially expressed proteins were identified in that study including S100 calcium binding protein A9 (S100A9) as one of the major downregulated proteins. In the present study, we carried out immunohistochemical validation of S100A9 in a large cohort of ESCC patients to determine the expression and subcellular localization of S100A9 in tumors and adjacent normal esophageal epithelia. Downregulation of S100A9 was observed in 67% (n = 192) of 288 different ESCC tumors, with the most dramatic downregulation observed in the poorly differentiated tumors (99/111). Expression of S100A9 was restricted to the prickle and functional layers of normal esophageal mucosa and localized predominantly in the cytoplasm and nucleus whereas virtually no expression was observed in the tumor and stromal cells. This suggests the important role that S100A9 plays in maintaining the differentiated state of epithelium and suggests that its downregulation may be associated with increased susceptibility to tumor formation.

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“…37 Cornulin is involved in cell cycle arrest at the G1/S checkpoint by upregulating the expression of p21(WAF/CIP). 38 Progression of renal failure in a subtotal nephrectomy model in p21 knockout mice was slower and associated with a 5-fold increase in epithelial surface compared with wild-type mice, suggesting that epithelial repair is hampered in the wild-type strain. Epithelial cell cycle arrest has been identified as a major promotor of kidney fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides

Schanstra

Zürbig

Alkhalaf

et al. 2015

Journal of the American Society of Nephrology

209

197

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Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303620.065; P,0.001) and integrated discrimination improvement (0.05860.014; P,0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.

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Characterization of Tumor Suppressive Function of cornulin in Esophageal Squamous Cell Carcinoma

Cited by 64 publications

References 40 publications

Altered Expression of Genes Encoding Cornulin and Repetin in Atopic Dermatitis

Altered Expression of Genes Encoding Cornulin and Repetin in Atopic Dermatitis

Downregulation of S100 Calcium Binding Protein A9 in Esophageal Squamous Cell Carcinoma

Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides

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