Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma

Qi, Yijun; Wang, Ming; Liu, Ruimin; Hua, Wei; Chao, Wei-Xia; Zhang, Tian; Lou, Qiang; Li, Xiumin; Ma, Jing; Zhu, Han; Yang, Zhenhua; Hai-qing, Liu; Ma, Yuanfang

doi:10.1371/journal.pone.0095386

Cited by 16 publications

(13 citation statements)

References 52 publications

(56 reference statements)

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“…In China, the morbidity and mortality of esophageal carcinoma accounted for the fifth and fourth of malignancy, respectively [2]. As the most common histological type of esophageal carcinoma in China, the 5‐year overall survival (OS) rate of esophageal squamous cell carcinoma (ESCC) patients after esophagectomy has significantly increased over the past several decades but remains approximately 20% [3–6]. However, the molecular mechanism of ESCC genesis and progression is not well understood, and biomarkers for predicting clinical outcome of ESCC patients are unavailable.…”

Section: Introductionmentioning

confidence: 99%

Expression and significance of ASPP2 in squamous carcinoma of esophagus

Liu

et al. 2018

The Kaohsiung J of Med Scie

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To study the significance of apoptosis stimulating protein of P53 2 (ASPP2) expression in esophageal squamous cell carcinoma (ESCC), immunohistochemistry S-P method was used to examine the expression of ASPP2 in 136 cases of ESCC, 35 cases of high grade intraepithelial neoplasia (HGIN), 29 cases of low grade intraepithelial neoplasia (LGIN) and 37 cases of normal esophageal epithelium (NEE). The associations of ASPP2 expression with clinicopathological data and overall survival (OS) were also analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate ASPP2 expression in a total of 20 matched human ESCC tumor tissues and normal adjacent tissues (NAT). In addition, EC109 cells were treated with cisplatin (CDDP) in vitro for 24 h (the intervention group) and the control group was set up at the same time. Western blot was used to examine the expression of ASPP2 protein between the two groups. The expression of ASPP2 decreased progressively from NEE to LGIN, to HGIN, and to ESCC, and it was related to TNM stage, histological differentiation and lymph node metastasis in ESCC (P < 0.05). ASPP2 was a protective factor of patients with ESCC (P = 0.008). The relative expression of ASPP2 mRNA was markedly downregulated in ESCC compared with the paired NAT (P < 0.01). Western blot results showed that cells in the intervention group could express ASPP2 while there was no expression of ASPP2 in the control group. Taken together, these results indicate that the abnormal expression of ASPP2 may play an important role for development and metastasis in ESCC.

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Section: Introductionmentioning

confidence: 99%

Expression and significance of ASPP2 in squamous carcinoma of esophagus

Liu

et al. 2018

The Kaohsiung J of Med Scie

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Section: Introductionmentioning

confidence: 99%

“…Esophageal squamous cell carcinoma (ESCC) is one of the frequently occurring digestive malignant diseases in China [ 1 , 2 ]. Patients with ESCC have higher mortality rates and 5-year survival rate is lower mainly because of local invasion, lymph node and distant metastasis [ 1 ]. Precise mechanisms of ESCC invasion and metastasis remain unclear, so further studies on the potential mechanisms involved in invasion and metastasis are critical for the improvement of prognosis for patients with ESCC.…”

Section: Introductionmentioning

confidence: 99%

MiR-424-5p participates in esophageal squamous cell carcinoma invasion and metastasis via SMAD7 pathway mediated EMT

Wang

Yang

et al. 2016

Diagn Pathol

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BackgroundsESCC is a life-threatening disease due to invasion and metastasis in the early stage. Great efforts had been made to detect the molecular mechanisms which led to the invasion and metastasis in ESCC. Recent evidence had suggested that deregulation of miR-424-5p took an important role in cancers. However, its role and functional mechanism in ESCC had seldom been elucidated.MethodsThe expression levels of miR-424-5p were detected in ESCC tissues and cell lines by real-time PCR methods. Then, the invasion, metastasis and proliferation ability of ESCC cell lines transfected with miR-424-5p mimics were analyzed separately by transwell invasion assay, wound healing assay and cell proliferation assay. Finally, the target gene of miR-424-5p was studied and verified by luciferase activity assay. And the role of miR-424-5p in EMT was also investigated by real-time PCR and western blot assay.ResultsWe showed that the expression levels of miR-424-5p were decreased both in ESCC tissues and cell lines. Furthermore, the expression levels of miR-424-5p were negatively linked to lymph node metastasis in ESCC tissues. Restoration of miR-424-5p in EC-1 cells by using miR-424-5p mimics could decrease the invasion, metastasis and proliferation of EC-1 cells, indicating its role in inhibition on the invasion and metastasis ability of ESCC cells and tissues. In addition, we demonstrated that SMAD7 was a specific target gene for miR-424-5p by luciferase activity assay and miR-424-5p could not only negatively regulate SMAD7 expression but also participate in EMT via SMAD7, because overexpression of SMAD7 could partly enhance the miR-424-5p anti-EMT function.ConclusionsOur results described that miR-424-5p -SMAD7 pathway contributed to ESCC invasion and metastasis and up-regulation of miR-424-5p perhaps provided a strategy for preventing tumor invasion, metastasis.

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“…Phosphate can bind to all of the 14-3-3 family and therefore being present at high intracellular concentration [ 4 , 5 ]. With roles of different 14-3-3 isoforms in a wide variety of signal transduction processes, 14-3-3 σ is the only isoform directly linked to cancer in epithelial cells, which is regulated by major tumor suppressor genes [ 6 – 8 ]. The stabilizing ring-ring and salt bridge interactions unique to the 14-3-3 σ homodimer structure are revealed by the x-ray crystal structure of 14-3-3 σ with binding peptide, which potentially destabilized electrostatic interactions between subunits in 14-3-3 σ -containing heterodimers, and rationalized preferential homodimerization of 14-3-3 σ in vivo.…”

Section: Introductionmentioning

confidence: 99%

Identification of 14-3-3 Proteins Phosphopeptide-Binding Specificity Using an Affinity-Based Computational Approach

Li¹,

Tang²,

Guo³

2016

PLoS ONE

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The 14-3-3 proteins are a highly conserved family of homodimeric and heterodimeric molecules, expressed in all eukaryotic cells. In human cells, this family consists of seven distinct but highly homologous 14-3-3 isoforms. 14-3-3σ is the only isoform directly linked to cancer in epithelial cells, which is regulated by major tumor suppressor genes. For each 14-3-3 isoform, we have 1,000 peptide motifs with experimental binding affinity values. In this paper, we present a novel method for identifying peptide motifs binding to 14-3-3σ isoform. First, we propose a sampling criteria to build a predictor for each new peptide sequence. Then, we select nine physicochemical properties of amino acids to describe each peptide motif. We also use auto-cross covariance to extract correlative properties of amino acids in any two positions. Finally, we consider elastic net to predict affinity values of peptide motifs, based on ridge regression and least absolute shrinkage and selection operator (LASSO). Our method tests on the 1,000 known peptide motifs binding to seven 14-3-3 isoforms. On the 14-3-3σ isoform, our method has overall pearson-product-moment correlation coefficient (PCC) and root mean squared error (RMSE) values of 0.84 and 252.31 for N–terminal sublibrary, and 0.77 and 269.13 for C–terminal sublibrary. We predict affinity values of 16,000 peptide sequences and relative binding ability across six permutated positions similar with experimental values. We identify phosphopeptides that preferentially bind to 14-3-3σ over other isoforms. Several positions on peptide motifs are in the same amino acid category with experimental substrate specificity of phosphopeptides binding to 14-3-3σ. Our method is fast and reliable and is a general computational method that can be used in peptide-protein binding identification in proteomics research.

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Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma

Cited by 16 publications

References 52 publications

Expression and significance of ASPP2 in squamous carcinoma of esophagus

Expression and significance of ASPP2 in squamous carcinoma of esophagus

MiR-424-5p participates in esophageal squamous cell carcinoma invasion and metastasis via SMAD7 pathway mediated EMT

Identification of 14-3-3 Proteins Phosphopeptide-Binding Specificity Using an Affinity-Based Computational Approach

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