S1PR1 Suppresses Lung Adenocarcinoma Progression Through P-STAT1/miR-30c-5 P/FOXA1 Pathway

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2024 Nov 17

PMID 39551792

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Sphingosine-1-Phosphate Metabolic Pathway in Cancer: Implications for Therapeutic Targets.

Rufail M, Bassi R, Giussani P Int J Mol Sci. 2025; 26(3).

PMID: 39940821 PMC: 11817292. DOI: 10.3390/ijms26031056.

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