Overexpressed FAM111B degrades GSDMA to promote esophageal cancer tumorigenesis and cisplatin resistance.

IF 4.9 2区医学 Q2 CELL BIOLOGY Cellular Oncology Pub Date : 2024-02-01 Epub Date: 2023-09-06 DOI:10.1007/s13402-023-00871-0

Haiqin Wang, Haohui Wang, Jiajing Chen, Pian Liu, Xiaoxiong Xiao

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Abstract

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.

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过表达的 FAM111B 能降解 GSDMA，从而促进食管癌肿瘤发生和顺铂耐药。

背景：顺铂等化疗药物常用于临床上无法切除或复发的食管癌（ESCA）患者。然而，患者往往会对顺铂产生耐药性，进而导致预后不良。研究表明，FAM111B 可能作为癌基因或抑癌基因参与肿瘤的发生发展。然而，FAM111B在ESCA中的病理作用和相应机制仍不清楚：方法：利用GEPIA网络工具、ENCORI泛癌分析平台和UALCAN-TCGA数据库研究FAM111B在ESCA中的表达。应用 CCK-8、血管生成、Transwell 和异种移植试验探讨 FAM111B 在 ESCA 中的生物学功能。应用Western印迹、RT-qPCR和RNA-seq分析研究FAM111B/GSDMA轴在ESCA细胞进展中的作用。CCK-8和异种移植试验用于研究FAM111B/GSDMA轴在决定ESCA对顺铂敏感性中的作用：结果：我们的研究结果表明，与正常组织相比，FAM111B在ESCA组织中高表达。结果：我们的研究结果表明，与正常组织相比，FAM111B在ESCCA组织中高表达。我们还发现，FAM111B通过与GSDMA结合促进ESCC细胞的进展，而胰蛋白酶蛋白酶结构域对FAM111B的活性至关重要。此外，我们还发现FAM111B/GSDMA轴调节ESCCA对顺铂的敏感性：总之，我们发现了一种新型的 FAM111B/GSDMA 轴，它至少在 ESCC 细胞中调控着 ESCA 的肿瘤发生和化疗敏感性。

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

Cellular Oncology ONCOLOGY-CELL BIOLOGY

CiteScore

10.30

自引率

1.50%

发文量

审稿时长

12 months

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.