SFXN1 介导的肺腺癌免疫细胞浸润和肿瘤发生：一个潜在的治疗靶点。

SFXN1-mediated immune cell infiltration and tumorigenesis in lung adenocarcinoma: A potential therapeutic target.

机构信息

Department of Anaesthesiology and Perioperative Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan 450003, China.

Medical Genetic Institute of Henan Province, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan 450003, China.

出版信息

Int Immunopharmacol. 2024 May 10;132:111918. doi: 10.1016/j.intimp.2024.111918. Epub 2024 Mar 26.

DOI:10.1016/j.intimp.2024.111918

PMID:38537539

Abstract

BACKGROUND

Sideroflexin 1 (SFXN1), a mitochondrial serine transporter implicated in one-carbon metabolism, is a prognostic biomarker in lung adenocarcinoma (LUAD). However, its role in LUAD progression remains elusive. This study aimed to investigate the functional significance of SFXN1 in LUAD and evaluate its potential as a therapeutic target.

METHODS

We analyzed SFXN1 expression and its diagnostic and prognostic value in LUAD using the Pan-cancer TCGA dataset. In vitro assays (CCK-8, cell cycle, EDU, wound-healing, and transwell) were employed to assess the role of SFXN1, complemented by in vivo experiments. RNA sequencing elucidated SFXN1-mediated cellular functions and potential mechanisms. Bulk RNA-seq and scRNA-seq data from TCGA and GEO were used to investigate the correlation between SFXN1 and the tumor immune microenvironment. RT-qPCR, Western blot, and IHC assays validated SFXN1 expression and its impact on the immune microenvironment in LUAD.

RESULTS

SFXN1 was upregulated in LUAD tissues and associated with poor prognosis. RNA-seq and scRNA-seq analyses revealed increased SFXN1 expression in tumor cells, accompanied by decreased infiltration of NK and cytotoxic T cells. SFXN1 knockdown significantly reduced cell proliferation and migration, and the inhibition of ERK phosphorylation and CCL20 expression may be the molecular mechanism involved. In vivo, targeting SFXN1 decreased Tregs infiltration and inhibited tumor growth.

CONCLUSIONS

Our findings suggest that SFXN1 may be a potential therapeutic target for LUAD treatment.

摘要

背景

丝氨酸载体蛋白 1（SFXN1）是一种与一碳代谢有关的线粒体丝氨酸转运蛋白，它是肺腺癌（LUAD）的预后生物标志物。然而，它在 LUAD 进展中的作用仍不清楚。本研究旨在探讨 SFXN1 在 LUAD 中的功能意义，并评估其作为治疗靶点的潜力。

方法

我们使用 Pan-cancer TCGA 数据集分析了 SFXN1 的表达及其在 LUAD 中的诊断和预后价值。通过 CCK-8、细胞周期、EDU、划痕愈合和 Transwell 等体外实验评估 SFXN1 的作用，并辅以体内实验。RNA 测序阐明了 SFXN1 介导的细胞功能和潜在机制。使用 TCGA 和 GEO 的批量 RNA-seq 和 scRNA-seq 数据来研究 SFXN1 与肿瘤免疫微环境之间的相关性。RT-qPCR、Western blot 和 IHC 检测验证了 SFXN1 在 LUAD 中的表达及其对免疫微环境的影响。

结果

SFXN1 在 LUAD 组织中上调，与预后不良相关。RNA-seq 和 scRNA-seq 分析显示肿瘤细胞中 SFXN1 表达增加，同时 NK 和细胞毒性 T 细胞浸润减少。SFXN1 敲低显著降低了细胞增殖和迁移，ERK 磷酸化和 CCL20 表达的抑制可能是涉及的分子机制。在体内，靶向 SFXN1 减少了 Tregs 的浸润并抑制了肿瘤生长。