背景:化学治疗剂如顺铂通常用于临床不可切除或复发性食管癌(ESCA)的患者。然而,患者经常对顺铂产生耐药性,这反过来又导致预后不良。研究表明,FAM111B可能作为癌基因或抑癌基因参与肿瘤的发展。然而,FAM111B在ESCA中的病理作用和相应机制尚不清楚。
方法:GEPIA网络工具,使用ENCORI泛癌分析平台和UALCAN-TCGA数据库研究FAM111B在ESCA中的表达。CCK-8,血管生成,应用Transwell和异种移植试验探讨FAM111B在ESCA中的生物学功能。蛋白质印迹,RT-qPCR,和RNA-seq分析用于研究ESCA细胞进展中的FAM111B/GSDMA轴。CCK-8和异种移植物测定用于研究FAM111B/GSDMA轴在确定ESCA对顺铂的敏感性中的作用。
结果:我们的结果表明,与正常组织相比,FAM111B在ESCA组织中高表达。我们表明FAM111B通过与GSDMA结合促进ESCC细胞的进展,并且胰蛋白酶蛋白酶结构域对于FAM111B的活性是必不可少的。此外,我们显示FAM111B/GSDMA轴调节ESCA中顺铂敏感性。
结论:总体而言,我们确定了一个新的FAM111B/GSDMA轴调节ESCA肿瘤发生和化学敏感性,至少在ESCC细胞中。
BACKGROUND: Chemotherapeutic agents such as cisplatin are commonly used in patients with clinically unresectable or recurrent esophageal cancer (ESCA). However, patients often develop resistance to cisplatin, which in turn leads to a poor prognosis. Studies have shown that FAM111B may be involved in the development of tumors as an oncogene or tumor suppressor gene. However, the pathological role and corresponding mechanism of FAM111B in ESCA are still unclear.
METHODS: The GEPIA web tool, ENCORI Pan-Cancer Analysis Platform and UALCAN-TCGA database were used to study the expression of FAM111B in ESCA. CCK-8, angiogenesis, Transwell and xenograft assays were applied to explore the biological function of FAM111B in ESCA. Western blot, RT-qPCR, and RNA-seq analyses were applied to study the FAM111B/
GSDMA axis in the progression of ESCA cells. CCK-8 and xenograft assays were used to study the role of the FAM111B/
GSDMA axis in determining the sensitivity of ESCA to cisplatin.
RESULTS: Our results demonstrated that FAM111B is highly expressed in ESCA tissues compared to normal tissues. We showed that FAM111B promotes the progression of ESCC cells by binding to
GSDMA and that the trypsin protease domain is essential for the activity of FAM111B. Furthermore, we showed that the FAM111B/
GSDMA axis regulates cisplatin sensitivity in ESCA.
CONCLUSIONS: Overall, we identified a novel FAM111B/
GSDMA axis regulating ESCA tumorigenesis and chemosensitivity, at least in ESCC cells.