SPHK1 promotes the migration and invasion of gastric cancer cells through NF-κB pathway

Abstract

Background: Gastric cancer (GC) is one of the most common malignant tumors. Sphingosine kinase-1 (SPHK1) is a member of the SPHK family of proteins,which are involved in the pathogenesis of various cancers. This study aimed to investigate SPHK1 expression in GC tissues, and its effects on the migration and invasion of GC cell lines. Methods: Bioinformatics predicted SPHK1 expression and prognosis. The expression of SPHK1 was detected by immunohistochemistry. Real-time PCR analysis was used to detect SPHK1mRNA expression. Cell migration was detected by cell scratch methods. Cell migration and invasion were detected by Transwell assays. Western Blotting was used to detect protein expression. Results: The expression of SPHK1 in GC was significantly higher than that in matched non-cancer tissues. Knockdown of SPHK1 can reduce the migration and invasion of GC cells, while overexpression of SPHK1 has the opposite effect. In addition, SPHK1 positively regulates protein levels of phosphorylated P65(p-P65), as well as protein expression of vascular endothelial growth factor A(VEGFA) and interleukin 17(IL-17) at transcriptional targets of the NF-κB signaling pathway. The blockage of the NF-κB signaling pathway by PDTC could reverse the SPHK1-promoted GC cell migration and invasion. Conclusions: Our results elucidate the key role of SPHK1 in promoting GC cell migration and invasion, and suggest that SPHK1 may be a potential molecular target for preventing GC metastasis.