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. 2024 Oct 28;14(18):7199–7218. doi: 10.7150/thno.102390

Figure 4.

Figure 4

SPHK1 regulated MMP1 expression via the MAPK signaling pathway. A. Enrichment plot of SPHK1 target gene sets based on RNA sequencing. B. Correlation analysis of specific MAPK subfamily direct upstream kinases of ERK, p38, and JNK with SPHK1 and MMP1. C-E. SAS and SCC15 cells were treated with sphk1-specific siRNA or siRNA NC for 48 h, and then cells were transduced for 24 h in the presence or absence of 10 µM of the following inhibitors: ERK1/2 inhibitor FR 180204 (FR), JNK inhibitor SP 600125 (SP), or p38 inhibitor SB 202190 (SB). MMP1 protein levels were then analyzed by western blotting. F. SAS and SCC15 cells were treated with sphk1-specific siRNA or siRNA NC for 48 h and then analyzed for phosphorylated and total ERK1/2, phosphorylated and total p38, and phosphorylated and total JNK by western blotting. G. Multiplex immunofluorescence staining of tumor tissues from five patients with HNSCC showed the ratio of SPHK1+/MMP1+ /phospho-ERK+ cells.