Objective This study aims to investigate the impact of Src homology region 2-containing protein tyrosine phosphatase 2(SHP2)inhibitor on the expression of inflammation-related genes in KRAS-mutant lung cancer cells, providing a foundational basis for personalized and precision therapies targeting KRAS-mutant lung cancer in the future.
Methods Five KRAS-mutant human lung cancer cell lines were treated with the SHP2 inhibitor SHP099. Western blot was conducted to assess the activation levels of ERK1/2 and other signaling pathway proteins. RNA sequencing was used to analyze the gene expression profiles of paired samples after SHP099/DMSO treatment. Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were used to reveal the enriched functional pathways of differentially expressed genes. Furthermore, RT-qPCR was employed to validate the relative expression levels of these genes.
Results Treatment with the SHP2 inhibitor resulted in a significant downregulation of p-SHP2 and p-ERK1/2 in KRAS-mutant lung cancer cells. Transcriptome sequencing and differential gene analysis demonstrated that the use of SHP2 inhibitor affected the expression of numerous genes, particularly downregulating inflammation-related genes such as CXCL1, CXCL2, CXCL8, MMP1, and PTGS2, which were associated with the interleukin 17(IL-17)pathway.
Conclusions SHP2 targeted inhibition significantly affects the expression of inflammation-related genes within the IL-17 signaling pathway in KRAS-mutant lung cancer cells, providing preliminary evidence for further exploring the potential of targeting SHP2 to regulate the immune microenvironment in lung cancer.
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