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.
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：Sideroflexin1（SFXN1），参与单碳代谢的线粒体丝氨酸转运蛋白，是肺腺癌（LUAD）的预后生物标志物。然而,其在LUAD进展中的作用仍然难以捉摸。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：我们使用泛癌TCGA数据集分析了SFXN1在LUAD中的表达及其诊断和预后价值。体外测定(CCK-8，细胞周期，EDU,伤口愈合,和transwell）用于评估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。使用来自TCGA和GEO的大量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,蛋白质印迹,和IHC分析验证了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，与不良预后相关。RNA-seq和scRNA-seq分析显示肿瘤细胞中SFXN1表达增加，伴有NK和细胞毒性T细胞浸润减少。SFXN1敲低显著降低细胞增殖和迁移，而抑制ERK磷酸化和CCL20表达可能是其分子机制。在体内,靶向SFXN1减少Tregs浸润并抑制肿瘤生长。
结论：我们的研究结果表明SFXN1可能是LUAD治疗的潜在治疗靶点。
方法：我们使用泛癌TCGA数据集分析了SFXN1在LUAD中的表达及其诊断和预后价值。体外测定(CCK-8，细胞周期，EDU,伤口愈合,和transwell）用于评估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。使用来自TCGA和GEO的大量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,蛋白质印迹,和IHC分析验证了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，与不良预后相关。RNA-seq和scRNA-seq分析显示肿瘤细胞中SFXN1表达增加，伴有NK和细胞毒性T细胞浸润减少。SFXN1敲低显著降低细胞增殖和迁移，而抑制ERK磷酸化和CCL20表达可能是其分子机制。在体内,靶向SFXN1减少Tregs浸润并抑制肿瘤生长。
结论：我们的研究结果表明SFXN1可能是LUAD治疗的潜在治疗靶点。
