582. LOW EXPRESSION OF FRG1 PROMOTES MIGRATION AND INVASION IN ESOPHAGEAL CANCER

IF 2.3 3区 医学 Q3 GASTROENTEROLOGY & HEPATOLOGY
Ya Zeng, Xi Su, Tongfang Zhou, Yunfeng Wang, Jingyi Jia, Jie Gao, Yuezhen Deng, Xiaolong Fu, Xuwei Cai
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Abstract

Purpose Distant metastasis is the primary cause of mortality among patients with esophageal cancer. Although FRG1 is known to play a role in the metastasis of various cancers, its specific function in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. In this study, we aimed to explore the role and potential molecular mechanism of FRG1 in the metastasis of ESCC. Methods Whole-exome sequencing was performed in ESCC patients who experienced distant metastasis (DM group) and those without metastasis within two years (non-DM group). Bioinformatics analysis and Immunohistochemistry (IHC) validation were conducted. In vitro, FRG1-overexpressed ESCC cell lines were established with lentivirus and validated by western blots. The wound-healing assay, transwell migration and invasion assay were performed in esophageal cancer cell lines. Additionally, RNA sequencing was conducted in ESCC cells to identify potential pathways involved. Results Mutations in FRG1 were more frequently observed in DM group compared to those in non-DM group. IHC revealed that the expression of FRG1 in DM group was significantly lower than non-DM group. In vitro, our results showed that ESCC cells with low FRG1 expression exhibited enhanced migration and invasion capabilities. Conversely, overexpression of FRG1 inhibited migration and invasion in ESCC cells. Mechanistically, RNA sequencing analysis showed a total of 93 differential expression genes between FRG1-overexpressed cells and the negative control. Notably, most differential genes were mainly enriched in the PPAR pathway and tyrosine metabolism pathway. Conclusion Our findings suggest that low FRG1 expression in patients may be indicative of rapid distant metastasis. The significant impact of FRG1's abnormal expression on the migration and invasion of ESCC cells highlights its potential as a therapeutic target for treating esophageal squamous cell carcinoma.
582.低表达的 frg1 促进食管癌的迁移和侵袭
目的 远处转移是食管癌患者死亡的主要原因。虽然已知 FRG1 在多种癌症的转移中发挥作用,但其在食管鳞状细胞癌(ESCC)中的具体功能尚未阐明。本研究旨在探讨 FRG1 在 ESCC 转移中的作用及其潜在的分子机制。方法 对发生远处转移的 ESCC 患者(DM 组)和两年内未发生转移的 ESCC 患者(非 DM 组)进行全外显子组测序。进行了生物信息学分析和免疫组化(IHC)验证。在体外,利用慢病毒建立了FRG1表达的ESCC细胞系,并通过Western印迹进行了验证。在食管癌细胞系中进行了伤口愈合试验、Transwell 迁移和侵袭试验。此外,还对 ESCC 细胞进行了 RNA 测序,以确定潜在的参与途径。结果 与非DM组相比,DM组中FRG1的突变更为常见。IHC显示,DM组中FRG1的表达明显低于非DM组。体外实验结果表明,FRG1 低表达的 ESCC 细胞具有更强的迁移和侵袭能力。相反,过表达 FRG1 会抑制 ESCC 细胞的迁移和侵袭。从机理上讲,RNA测序分析表明,FRG1表达过高的细胞与阴性对照之间共有93个差异表达基因。值得注意的是,大多数差异基因主要富集在 PPAR 通路和酪氨酸代谢通路中。结论 我们的研究结果表明,患者体内 FRG1 的低表达可能预示着快速的远处转移。FRG1 的异常表达对 ESCC 细胞的迁移和侵袭有重大影响,这突显了其作为食管鳞状细胞癌治疗靶点的潜力。
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来源期刊
Diseases of the Esophagus
Diseases of the Esophagus 医学-胃肠肝病学
CiteScore
5.30
自引率
7.70%
发文量
568
审稿时长
6 months
期刊介绍: Diseases of the Esophagus covers all aspects of the esophagus - etiology, investigation and diagnosis, and both medical and surgical treatment.
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