Anti-oncogenic mechanism of KLF17 in colon cancer by repressing cell migration and invasion via FHL1 upregulation.

Colon cancer is a disease with high prevalence worldwide. This study sought to investigate Kruppel-like factor 17 (KLF17) mechanism in the development of colon cancer through four-and-a-half-LIM domain protein 1 (FHL1). In colon cancer cells, KLF17 and FHL1 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. After gain- and loss-of-function experiments in colon cancer cells, cell proliferative, invasive, and migrating abilities were tested by cell counting kit-8, transwell, and scratch assays, respectively. The expression of epithelial-mesenchymal transition (EMT)-related genes, E-cadherin, N-cadherin, and Vimentin, was measured by RT-qPCR and Western blot. Chromatin immunoprecipitation and dual-luciferase reporter gene assays were performed to detect the binding of KLF17 and the FHL1 promoter. Finally, a transplantation tumor model in nude mice was established for in vivo validation. Mechanistically, KLF17 facilitated FHL1 transcription by binding to the FHL1 promoter. KLF17 or FHL1 upregulation suppressed the colon cancer cell proliferative, invasive, and migrating capacities, accompanied by elevated E-cadherin expression and diminished N-cadherin and Vimentin expression. Furthermore, FHL1 silencing abrogated the repressive impacts of KLF17 upregulation on colon cancer cell EMT, proliferative, invasive, and migrating capabilities. Furthermore, KLF17 augmented FHL1 expression and curtailed the growth of transplanted tumors in nude mice. Conclusively, KLF17 promoted FHL1 transcription, thereby impeding the invasion, migration, and EMT of colon cancer cells.