S1PR1 通过 p-STAT1/miR-30c-5 p/FOXA1 通路抑制肺腺癌的进展。

IF 11.4 1区 医学 Q1 ONCOLOGY
Yanfei Chai, Hong Xiang, Yuchao Ma, Wei Feng, Zhibin Jiang, Qianjun Zhu, Yingji Chen, Quanjun Liu, Jing Zhang, Jie Ouyang, Peng Gao, Xiao Zhang, Shuhua Chen, Longyu Jin, Hongwei Lu
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引用次数: 0

摘要

背景:两性鞘氨醇-1-磷酸受体1(S1PR1)被认为与多种恶性肿瘤密切相关,但S1PR1在肺腺癌中的作用和机制尚不完全清楚。本研究旨在探讨 S1PR1 在肺腺癌(LUAD)恶性生物学功能中的作用及下游信号通路:方法:采用生物信息学分析、RT-qPCR、western blot和免疫组织化学(IHC)等方法研究S1PR1在LUAD中的表达。同时还分析了 S1PR1 的预后。为研究 S1PR1 对 LUAD 的影响,进行了 CCK-8 试验、集落形成试验、划痕试验、Transwell 迁移和侵袭试验以及细胞粘附试验。采用 RNA 测序分析了过表达 S1PR1 的 LUAD 细胞中的 DEGs。染色质免疫沉淀(ChIP)和双荧光素酶报告实验验证了 FOXA1 与靶基因之间的直接调控。通过双荧光素酶报告实验确定了miRNA-30c-5p是调控FOXA1的微RNA。检测了S1PR1的下游信号通路,以明确调控miRNA-30c-5p的特定通路:结果:S1PR1在LUAD中明显减少,并与预后呈正相关。过表达 S1PR1 可抑制 COL5A1、MMP1 和 SERPINE1 的表达,从而抑制 LUAD 细胞的增殖、迁移、侵袭和粘附功能。FOXA1 是调节 MMP1、COL5A1 和 SERPINE1 表达的关键转录因子。S1PR1通过p-STAT1/miR-30c-5p抑制FOXA1的表达,从而抑制LUAD细胞的恶性功能:结论:S1PR1在LUAD中表达下调,与预后呈正相关。S1PR1通过p-STAT1/miR-30c-5p/FOXA1信号通路抑制COL5A1、MMP1和SERPINE1的表达,从而调节LUAD细胞的恶性功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
S1PR1 suppresses lung adenocarcinoma progression through p-STAT1/miR-30c-5 p/FOXA1 pathway.

Background: Sphingosine-1-phosphate receptor 1 (S1PR1) is considered to be closely related to a variety of malignant tumors, but the role and mechanism of S1PR1 in lung adenocarcinoma are not fully understood. In this study, we aim to explore the role and downstream signaling pathways of S1PR1 in the malignant biological functions of lung adenocarcinoma (LUAD).

Methods: Bioinformatics analysis, RT-qPCR, western blot and immunohistochemistry (IHC) were was used to investigate the expression of S1PR1 in LUAD. The prognosis of S1PR1 was also analyzed. CCK-8 assay, colony formation assay, scratch assay, transwell migration and invasion assay, cell adhesion assay were performed to examine the effect of S1PR1 on LUAD. RNA sequencing was employed to analyze the DEGs in LUAD cells overexpressing S1PR1. Enrichment pathway analysis using KEGG, GO, and GSEA was conducted to predict potential signaling pathways and downstream targets. chromatin immunoprecipitation (ChIP) and dual luciferase reporter assay were performed to verify the direct regulation between FOXA1 and the target genes. Then FOXA1 overexpression were performed to functional rescue experiments. miRNA-30c-5p was identified as a microRNA regulating FOXA1 by dual luciferase reporter assay. The downstream signaling pathways of S1PR1 was detected to clarify the specific pathways to regulates miR-30c-5p.

Results: S1PR1 is significantly decreased in LUAD and is positively correlated with the prognosis. Overexpression of S1PR1 inhibits the proliferation, migration, invasion and adhesion function of LUAD cells by suppressing the expression of COL5A1, MMP1, and SERPINE1. FOXA1 is a key transcription factor regulating the expression of MMP1, COL5A1 and SERPINE1. S1PR1 inhibits the expression of FOXA1 through p-STAT1/miR-30c-5p, thereby suppressing the malignant function of LUAD cells.

Conclusions: The expression of S1PR1 is downregulated in LUAD, which is positively correlated with prognosis. S1PR1 regulates the malignant function of LUAD cells by inhibiting the expression of COL5A1, MMP1 and SERPINE1 through the p-STAT1/miR-30c-5p/FOXA1 signaling pathway.

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来源期刊
CiteScore
18.20
自引率
1.80%
发文量
333
审稿时长
1 months
期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
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