The importance of Sphingosine kinase 1 isoform expression in the gut-liver axis

Publication Type:
Conference Proceeding
Annals of Oncology, 2021, 32, pp. S197-S197
Issue Date:
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Background: The sphingosine kinase 1 (SphK1) isoenzyme synthesises sphingosine-1-phosphate (S1P) 1 and plays a critical role in gut-liver diseases such as fatty liver, inflammatory bowel diseases and colon cancers. SphK1 is expressed as two major isoforms, SphK1a and SphK1b, both presenting common and distinct interacting functions depending on tissue type and location within the cell. Here, in this report, we examined the expression of SphK1 isoforms in normal and cancer human liver tissues and compare the isoform expression with different cells and tissue types and explore its relevance to the diagnosis and treatment of liver cancer. The overall aim of the study was to determine the SphK1 isoform status and importance in the liver and liver cancer. Methods: Polymerase chain reaction (PCR) primers were designed overlapping the SphK1a-b region and within the SphK1a region to differentiate the two isoforms. Qualitative RTPCR was used to determine the status of the SphK1a and SphK1b expression in normal and cancer cells lines, and in human tissue samples from patients with liver cancer (hepatocellular carcinoma). Results: Overall SphK1a is the most dominant isoform expressed in most tissue types whereas SphK1b is cell and tissue type specific. In cancer and adjacent liver tissue strong expression of SphK1a is detected, while SphK1b is not detected in the same samples and cell lines. Conclusion: Our data suggest that overall SphK1a is the predominant isoform in most cell lines and human tissues whilst SphK1b is cell and tissue type specific. In cells associated with the gut-liver axis only SphK1a is detected suggesting that SphK1a expression is important for normal gut-liver function, whereby the lack of SphK1b expression indicates that this isoform function may be redundant in this tissue. Although we see no observable change in SphK1a expression in cancer and adjacent liver tissues its strong expression may still influence disease outcome given that knocking out SphK1 offered protection from liver accumulation and inflammation in a mouse model.
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