TFAP2A-mediated Transcriptional Activation of ELMO1 Inhibits Ferroptosis and Promotes Esophageal Squamous Cell Carcinoma Progression.

IF 2.5 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Biotechnology Pub Date : 2025-09-13 DOI:10.1007/s12033-025-01511-8

Zhensheng Deng, Jinghong Xu, Zhenguo Liu

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引用次数: 0

Abstract

The role of engulfment and cell motility protein 1 (ELMO1) in esophageal squamous cell carcinoma (ESCC) is still unknown, even though it is critical for cellular behaviors. Our bioinformatics analyses have predicted transcription factor AP-2 alpha (TFAP2A) as a potential upstream regulator of ELMO1, suggesting its involvement in ESCC progression. ELMO1 expression in ESCC cells was analyzed. Lentivirus-mediated gene silencing was conducted, while cell counting kit-8, wound healing, and transwell assays evaluated the effects of ELMO1 on ESCC cell activities. The transcriptional regulatory effect of TFAP2A on ELMO1 was verified using dual-luciferase reporter assays and ChIP-qPCR. Additionally, ferroptosis-related indicators were detected to explore the potential role of TFAP2A/ELMO1 in ESCC. A nude mouse xenograft model was established to analyze tumor growth in vivo. ELMO1 was upregulated in KYSE150 cells. Silencing of ELMO1 suppressed ESCC cell migration and invasion, while sensitizing cells to ferroptosis. TFAP2A transcriptionally activated ELMO1 by binding to its promoter, thereby enhancing ESCC cell invasive potential. In vivo, TFAP2A knockdown activated ferroptosis and inhibited tumor growth, whereas ELMO1 overexpression promoted tumor progression. TFAP2A facilitates ESCC cell proliferation, migration, and invasion by promoting ELMO1 transcription and inhibiting ferroptosis. Both TFAP2A and ELMO1 act as oncogenic drivers in ESCC and may represent potential therapeutic targets.

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tfap2a介导的ELMO1转录激活抑制铁下垂并促进食管鳞状细胞癌进展。

吞噬和细胞运动蛋白1 （ELMO1）在食管鳞状细胞癌（ESCC）中的作用尚不清楚，尽管它对细胞行为至关重要。我们的生物信息学分析预测转录因子AP-2 α (TFAP2A)是ELMO1的潜在上游调节因子，表明其参与ESCC的进展。分析ELMO1在ESCC细胞中的表达。通过慢病毒介导的基因沉默，细胞计数试剂盒-8、伤口愈合和transwell实验评估ELMO1对ESCC细胞活性的影响。采用双荧光素酶报告基因法和ChIP-qPCR验证TFAP2A对ELMO1的转录调控作用。此外，通过检测凋亡相关指标，探讨TFAP2A/ELMO1在ESCC中的潜在作用。建立裸鼠异种移植瘤模型，分析肿瘤在体内的生长情况。ELMO1在KYSE150细胞中表达上调。ELMO1的沉默抑制了ESCC细胞的迁移和侵袭，同时使细胞对铁凋亡敏感。TFAP2A通过结合ELMO1的启动子转录激活ELMO1，从而增强ESCC细胞的侵袭潜能。在体内，TFAP2A敲低激活铁下垂并抑制肿瘤生长，而ELMO1过表达促进肿瘤进展。TFAP2A通过促进ELMO1转录和抑制铁下垂促进ESCC细胞增殖、迁移和侵袭。TFAP2A和ELMO1在ESCC中都是致癌驱动因子，可能代表潜在的治疗靶点。

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

Molecular Biotechnology 医学-生化与分子生物学

CiteScore

4.10

自引率

3.80%

发文量

165

审稿时长

6 months

期刊介绍： Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.