FOXA3: A Novel Tumor Suppressor in Esophageal Squamous Cell Carcinoma

IF 2.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2025-02-18 DOI:10.1002/jgm.70009

Siang Zhang, Yuxiang Jin, Qianyu Han, Xuewei Zhao, Lei Xue

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Abstract

Background

The forkhead box A (FOXA) family has been extensively studied in cancer research; however, the role of FOXA3 in malignant tumors, particularly esophageal squamous cell carcinoma (ESCC), is not well understood. This study explores the expression and function of FOXA3 in ESCC, assessing its potential as a prognostic marker and therapeutic target.

Methods

This study analyzed FOXA3 expression in ESCC tissues and its correlation with patient prognosis. The effects of FOXA3 overexpression on ESCC cell proliferation, migration, and invasion were examined in ESCC cell lines in vitro. Additionally, an in vivo tumorigenesis assay was performed using subcutaneous injection to assess the impact of FOXA3 overexpression on tumor growth. Statistical analyses were conducted to determine the significance of the results.

Results

FOXA3 expression was significantly reduced in ESCC tissues compared with it in paired adjacent normal tissues, and low FOXA3 expression was significantly associated with poor prognosis in ESCC patients. FOXA3 overexpression markedly inhibited ESCC cell proliferation, migration, and invasion. In addition, overexpression of FOXA3 repressed tumor growth in mice.

Conclusions

These findings indicate that FOXA3 acts as a tumor suppressor in ESCC, and its low expression is linked to poor outcomes. FOXA3 may serve as a potential diagnostic and therapeutic target for ESCC.

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FOXA3：食管癌中一种新的抑癌因子

叉头盒A （FOXA）家族在癌症研究中被广泛研究；然而，FOXA3在恶性肿瘤，特别是食管鳞状细胞癌（ESCC）中的作用尚不清楚。本研究探讨FOXA3在ESCC中的表达和功能，评估其作为预后标志物和治疗靶点的潜力。方法分析FOXA3在ESCC组织中的表达及其与患者预后的关系。在体外培养的ESCC细胞株中，研究FOXA3过表达对ESCC细胞增殖、迁移和侵袭的影响。此外，通过皮下注射进行体内肿瘤发生实验，以评估FOXA3过表达对肿瘤生长的影响。进行统计分析以确定结果的显著性。结果FOXA3在ESCC组织中的表达明显低于配对的邻近正常组织，FOXA3的低表达与ESCC患者的不良预后显著相关。FOXA3过表达明显抑制ESCC细胞的增殖、迁移和侵袭。此外，FOXA3的过表达抑制了小鼠的肿瘤生长。结论FOXA3在ESCC中发挥抑癌作用，其低表达与预后不良有关。FOXA3可能是ESCC潜在的诊断和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.