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ABSTRACT:
PROVIDER: PRJNA903384 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Esophageal squamous cell carcinoma (ESCC) is a serious malignant tumor, it affects human health. We analyzed the correlation between serum Stathmin levels and ESCC, further elucidated the molecular mechanisms how Stathmin promotes ESCC cell invasion and metastasis. Methods: Stathmin levels in ESCC and healthy control serum was detected by enzyme-linked immunosorbent assay (ELISA), and analyzed the clinical parameters. We established ESCC cells with Stathmin overexpression or knockdown, next evaluated the effects of Stathmin on invasion, metastasis and proliferation in ESCC. The expression levels of the integrin family, focal adhesion kinase (FAK) protein and extracellular signal-regulated kinase (ERK) were detected by immunoblotting. Results: Serum levels of Stathmin were significantly higher in ESCC and associated with lymph node metastasis, tumor stage and size. Furthermore, we found Stathmin promotes migration, invasion and proliferation of ESCC cells in vitro and in vivo. Further study confirmed that the activation of integrinα5β1/FAK/ERK pathway is increased in Stathmin overexpression cells, this pathway contribute to strengthen cell adhesion. Stathmin accelerates the cell motility by enhancing cell adhesion ability. Conclusion: Stathmin may be a potential biomarker for ESCC clinical detection, and it can promotes ESCC cell invasion and metastasis through the integrinα5β1/FAK/ERK pathway. The differentially expressed genes were analyzed by Human Transcriptome Array, and confirmed by RT-PCR.
2016-11-29 | GSE90578 | GEO
Project description:A proportion of superficial esophageal squamous cell carcinoma, a type of less invasive esophageal squamous cell carcinoma (ESCC), would have metastasis after esophagectomy or endoscopic resection with poor prognosis. The purpose of this study was to discover the whole-genome copy number alteration (CNA) profiles of superficial ESCC and compare the CNAs of superficial ESCC patients with and without metastasis after surgery. Thirty eight superficial ESCC cases, including 19 cases with metastasis and 19 cases without metastasis within 5 years after surgery, were analyzed CNAs by Affymetrix OncoScan™ FFPE Assay. A 39-gene signature was initially constructed to identify high risk of metastasis in superficial ESCC patients. In addition, amplification of 11q13.3 (FGF4) and deletion of 9p21.3 (CDKN2A) were identified as recurrent CNAs across all 38 superficial ESCC cases. And amplifications of 3p26.33 (SOX2-OT), 8q24.21 (MYC), 14q21.1 (FOXA1) and deletion of 3p12.1 (GBE1) were identified as recurrent CNAs among metastasis cases only. Our study provided a 39-gene signature tool to identified high risk metastasis in superficial ESCC and suggested that amplifications of SOX2-OT, MYC, FOXA1 genes and deletion of GBE1 gene might play a vital role in metastasis among superficial ESCC.
2017-06-10 | GSE78926 | GEO
Project description:Dysregulation of MOF (MYST1, KAT8), a highly conserved H4K16 acetyltransferase, plays important roles in human cancers. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we report that MOF is highly expressed in ESCC tumors and predicts a worse prognosis. Depletion of MOF in ESCC significantly impedes tumor growth and metastasis both in vitro and in vivo, whereas ectopic expression of MOF but not enzyme inactive mutant (MOF E350Q) promotes ESCC progression, suggesting that MOF acetyltransferase activity is crucial for its oncogenic activity. Further analysis reveals that USP10, a deubiquitinase highly expressed in ESCC, binds to and protects MOF from proteosome-dependent protein degradation. MOF stabilization by USP10 promotes H4K16ac enrichment in the ANXA2 promoter to stimulate ANXA2 transcription, which subsequently activates Wnt/ β-Catenin signaling to facilitate ESCC progression. Our findings highlight a novel USP10/MOF/ANXA2 axis as a promising therapeutic target for ESCC.
2024-01-09 | GSE241066 | GEO
Project description:Background: Esophageal squamous cell carcinoma (ESCC) has become an important global health issue. The M2 polarization of tumor-associated macrophages (TAMs) plays a key role in the occurrence and development of ESCC. It is reported that exosome circRNAs are involved in the regulation of the polarization state of TAMs, but the underlying mechanism remains unclear. In this study, we aim to identify novel exosome circrnas that regulate the progression of ESCC and explore their biological functions and regulatory mechanisms in ESCC. Method: The highly expressed circRNAs in ESCC tissues and plasma were identified by circRNA microarray analysis. Transmission electron microscopy, differential centrifugation and Western blotting were used for the presence of exosome circAP2B, and the uptake of circAP2B1 by macrophages was determined by exosome tracing. The effects of exosome circAP2B1 on tumor proliferation and metastasis were investigated in vitro and in vivo. The role and molecular mechanism of exosome circAP2B1 in enhancing mitochondrial homeostasis of macrophages to induce M2 polarization were investigated by means of flow cytometry analysis, IP, LC-MS/MS, RIP, Pull down, CHIP, CHRIP and dual-luciferase reporter gene. Result: We demonstrated that the upregulation of exosome circAP2B1 expression was positively correlated with lymph node metastasis and poor prognosis in patients with ESCC. Functionally, exosome circAP2B1 promotes the growth and metastasis of ESCC both in vitro and in vivo by inducing TMS-M2 polarization. Mechanism speaking, the tumor-derived exosome circAP2B1 enters macrophages to promote the nuclear translocation of the circAP2B1/ESRRA/KPNA1 ternary complex and mediate the transcriptional regulation of MFN2 to enhance the mitochondrial homeostasis of TAMs. Conclusion: The exosome circAP2B1 derived from ESCC cells induces TMS-M2 polarization and tumor progression by regulating mitochondrial metabolic reprogramming in macrophages. Therefore, circAP2B1 targeting exosome packaging may provide potential diagnostic and therapeutic strategies for ESCC.
2025-05-15 | GSE296251 | GEO
Project description:Objective: Esophageal squamous carcinoma (ESCC) is one of the most common gastrointestinal tumors, and the PI3K/AKT signaling pathway plays a key role in the development of ESCC. circRNAs have been reported to be involved in the regulation of PI3K/AKT signaling, but the underlying mechanisms are unclear. This study aimed to identify protein-coding circRNAs and investigate their function in ESCC. Design: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. A novel protein encoded by circ-PDE5A was identified by LC-MS/MS. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circ-PDE5A and its encoded PDE5A-500aa novel protein in ESCC. Construction of a nanoplatform for the coupling of circRNAs to investigate the therapeutic translation value of circ-PDE5A. Results: We found that circ-PDE5A expression was downregulated in ESCC cells and tissues, and its low expression was associated with later clinicopathological staging and poorer prognosis. Functionally, circ-PDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding the novel PDE5A-500aa protein, which was identified as a key player in regulating PI3K/AKT signaling activation in ESCC. Mechanistically, the novel PDE5A-500aa protein binds directly to PIK3IP1 and promotes USP14-mediated deubiquitination of the k48-linked polyubiquitin chain at residue K198 of PIK3IP1, thereby attenuating PI3K/AKT pathway in ESCC. In addition, the circ-PDE5A plasmid-coupled reduction-responsive nanoplatform successfully inhibited ESCC growth and metastasis. Conclusions: circ-PDE5A represents an epigenetic mechanism regulating PI3K/ATK signaling and serves as a novel and promising therapeutic target and prognostic marker for ESCC.
2024-01-15 | GSE250413 | GEO
Project description:To identify the candidate exosomal miRNAs involved in ESCC metastasis, we conducted small RNA sequencing to determine the miRNA expression profiles of plasma exosomes from 5 LNM+ and 5 LNM- ESCC patients
2022-10-02 | GSE214259 | GEO
Project description:Lung metastasis is a major cause of death in patients with esophageal squamous cell carcinoma (ESCC) and its tumor microenvironment (TME) is highly complex; however, the molecular mechanisms of ESCC lung metastasis are unclear. In this study, the first comprehensive single-cell atlas of ESCC lung metastasis is established using single-cell RNA sequencing of 11 patient samples. The findings highlight the dynamic evolutionary patterns of the TME and distinct characteristics of key cellular subpopulations. The immune microenvironment exhibited significant alterations, with a subpopulation of pro-carcinogenic cancer-associated fibroblasts (CAFs) in primary ESCC foci and lung metastases. Notably, calreticulin CDH11 is exclusively expressed in these CAFs and upregulated in conjunction with lung metastasis of ESCC. CDH11 modulates the AKT-related signaling pathway through its interaction with FGFR1, influencing CAF-mediated extracellular matrix remodeling, thereby facilitating metastatic progression. Application of the CDH11 inhibitor, celecoxib, presents a promising new strategy for targeting lung metastasis in ESCC. The molecular mechanisms underlying the lung metastatic microenvironment of ESCC, which are expected to improve the molecular typing accuracy of ESCC lung metastasis to the single-cell level contribute to the development of a precision therapeutic system based on the modulation of the stromal microenvironment, with significant clinical translational potential.
2025-09-29 | GSE309393 | GEO
Project description:Lung metastasis is a major cause of death in patients with esophageal squamous cell carcinoma (ESCC) and its tumor microenvironment (TME) is highly complex; however, the molecular mechanisms of ESCC lung metastasis are unclear. In this study, the first comprehensive single-cell atlas of ESCC lung metastasis is established using single-cell RNA sequencing of 11 patient samples. The findings highlight the dynamic evolutionary patterns of the TME and distinct characteristics of key cellular subpopulations. The immune microenvironment exhibited significant alterations, with a subpopulation of pro-carcinogenic cancer-associated fibroblasts (CAFs) in primary ESCC foci and lung metastases. Notably, calreticulin CDH11 is exclusively expressed in these CAFs and upregulated in conjunction with lung metastasis of ESCC. CDH11 modulates the AKT-related signaling pathway through its interaction with FGFR1, influencing CAF-mediated extracellular matrix remodeling, thereby facilitating metastatic progression. Application of the CDH11 inhibitor, celecoxib, presents a promising new strategy for targeting lung metastasis in ESCC. The molecular mechanisms underlying the lung metastatic microenvironment of ESCC, which are expected to improve the molecular typing accuracy of ESCC lung metastasis to the single-cell level contribute to the development of a precision therapeutic system based on the modulation of the stromal microenvironment, with significant clinical translational potential.
2025-09-29 | GSE309392 | GEO
Project description:Objective: Esophageal squamous carcinoma (ESCC) is one of the most common gastrointestinal tumors, and the PI3K/AKT signaling pathway plays a key role in the development of ESCC. circRNAs have been reported to be involved in the regulation of PI3K/AKT signaling, but the underlying mechanisms are unclear. This study aimed to identify protein-coding circRNAs and investigate their function in ESCC. Design: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. A novel protein encoded by circ-PDE5A was identified by LC-MS/MS. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circ-PDE5A and its encoded PDE5A-500aa novel protein in ESCC. Construction of a nanoplatform for the coupling of circRNAs to investigate the therapeutic translation value of circ-PDE5A. Results: We found that circ-PDE5A expression was downregulated in ESCC cells and tissues, and its low expression was associated with later clinicopathological staging and poorer prognosis. Functionally, circ-PDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding the novel PDE5A-500aa protein, which was identified as a key player in regulating PI3K/AKT signaling activation in ESCC. Mechanistically, the novel PDE5A-500aa protein binds directly to PIK3IP1 and promotes USP14-mediated deubiquitination of the k48-linked polyubiquitin chain at residue K198 of PIK3IP1, thereby attenuating PI3K/AKT pathway in ESCC. In addition, the circ-PDE5A plasmid-coupled reduction-responsive nanoplatform successfully inhibited ESCC growth and metastasis. Conclusions: circ-PDE5A represents an epigenetic mechanism regulating PI3K/ATK signaling and serves as a novel and promising therapeutic target and prognostic marker for ESCC.
2024-01-15 | GSE250323 | GEO