KLF13 promotes esophageal cancer progression and regulates triacylglyceride and free fatty acid metabolism through GPIHBP1.

Abstract

Kruppel-Like Factor 13 (KLF13) has strong effects on cancer occurrence and progression. Nevertheless, the role of KLF13 in oesophagal cancer (EC) remain elusive. In this study, we detected the expression of KLF13 in EC tissues and cells using immunohistochemistry, western blot, and real-time PCR, and found that KLF13 was upregulated in EC tissues and cells compared to normal controls. High expression of KLF13 indicated a poor prognosis for EC patients. Further, function studies in vitro and in vivo were performed to explore the role of KLF13 in EC cell progression. The results revealed that KLF13 knockdown suppressed EC cell proliferation, migration, epithelial-mesenchymal transition, increased cell apoptosis and cell cycle arrest in vivo and inhibited tumour growth in vitro. Conversely, KLF13 overexpression in EC cells had the opposite consequences. Mechanically, differentially expressed genes downstream of KLF13 were identified by RNA-seq and ChIP-seq. We found that there is a positive correlation between triacylglyceride and free fatty acid levels and KLF13 expression levels. A lipid-related gene, Glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1), was identified as a downstream gene of KLF13 using luciferase and chromatin immunoprecipitation assays, whose expression was positively regulated by KLF13. Finally, in vitro and in vivo recovery assays using shRNAs and overexpression plasmids confirmed that KLF13 has an oncogenic role in EC progression through GPIHBP1. Collectively, KLF13 can promote EC progression, triacylglyceride and free fatty acid metabolism through GPIHBP1. Therefore, molecular therapies targeting KLF13 and GPIHBP1 may be effective treatments against EC.