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SPHK1 Promotes the Migration and Invasion of Gastric Cancer Cells via NF-ΚB Signaling Pathway

*Corresponding Author:

Received Date: Mar 12, 2024 / Published Date: Apr 23, 2025

Citation: Zhu B, Ling Q, Ji K, Guan J, Wang R (2025) SPHK1 Promotes the Migration and Invasion of Gastric Cancer Cells via Nf-Κb Signaling Pathway. Diagnos Pathol Open 10: 250.

Copyright: © 2025 Zhu B, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

 
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Abstract

Background: Gastric Cancer (GC) is one of the most common malignancy in digestive system. Sphingosine Kinase-1 (SPHK1) is a member of the SPHK family of proteins, which is involved in the pathogenesis of various cancers. This study aims to investigate SPHK1 expression in GC tissues and its effects on the migration and invasion of GC cells.

Methods: SPHK1 expression and prognosis were analyzed by bioinformatics and Immunohistochemistry (IHC). SPHK1mRNA expression was detected through by Real-Time PCR (qRT-PCR). The enrichment pathway of SPHK1 was predicted by public databases. Cell migration was detected by cell scratch methods. Cell migration and invasion were detected by Transwell assays. Protein expression was detected through Western blotting.

Results: High expression of SPHK1 was observed in GC tissues and correlated with poor prognosis. IHC and qRT-PCR analyses revealed upregulation of SPHK1 expression in GC tissues. Knockdown of SPHK1 reduced the migration and invasion of GC cells, while overexpression of SPHK1 has the opposite result. Mechanistically, SPHK1 positively regulated 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 Nuclear Factor-κB (NF-κB/P65) signaling pathway. Blocking the NF-κB pathway with PDTC attenuated SPHK1-promoted migration and invasion of GC cells.

Conclusion: Our results elucidate the key role of SPHK1 in promoting migration and invasion of GC cells and suggest that SPHK1 may be a potential molecular target for preventing GC metastasis.

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