STK39 Enhances the Progression of Cholangiocarcinoma via PI3K/AKT Pathway

Abstract

Cholangiocarcinoma (CCA) is a highly aggressive form of liver cancer, but its pathogenesis is far from being fully elucidated. Recent studies have reported that Serine/threonine kinase 39 (STK39) is overexpressed in various tumor tissues and plays an essential role in tumor progression. However, the role of STK39 in CCA is still unclear. In this study, we investigated the clinical value as well as the potential functions and mechanisms of STK39 in CCA. The results showed that STK39 was overexpressed in CCA and negatively associated with the prognosis of CCA patients. Functionally, STK39 knockdown suppressed cell proliferation, migration, and invasion, while overexpression of STK39 facilitated tumor aggressiveness. In addition, STK39 knockdown was shown to induce G2/M phase cell cycle arrest and promote cell apoptosis. The tumor-promoting effects of STK39 in CCA were also validated by in vivo experiments. Mechanistically, RNA-seq analysis identified that STK39 positively regulated the PI3K/AKT pathway, and STK39 knockdown decreased the PI3K and AKT phosphorylation levels without changing the total protein levels. Combined with in vitro experiment results, STK39 was shown to function as an oncogene in CCA progression by activating PI3K/AKT signaling pathway. Furthermore, overexpression of STK39 could induce gemcitabine resistance in CCA cells. Moreover, we found that the increased expression of STK39 may be mediated by the dysregulation of miR-26a-5p. In summary, this study illustrates that STK39 may exert its oncogenic function in CCA through activating PI3K/AKT signaling pathway and could be served as a valuable prognostic candidate and a potential therapeutic target of CCA.