USP9X promotes apoptosis in cholangiocarcinoma by modulation expression of KIF1B? via deubiquitinating EGLN3

Abstract Background Cholangiocarcinoma represents the second most common primary liver malignancy. The incidence rate has constantly increased over last decades. silent nature limits early diagnosis and prevents efficient treatment. Methods Immunoblotting immunohistochemistry were used to assess expression profiling of USP9X EGLN3 in cholangiocarcinoma patients. ShRNA was silence gene expression. Cell apoptosis, cell cycle, CCK8, clone formation, shRNA interference xenograft mouse model explore biological function EGLN3. underlying molecular mechanism determined by immunoblotting, co-immunoprecipitation quantitative real time PCR (qPCR). Results Here we demonstrated that is downregulated which contributes tumorigenesis. inhibited proliferation colony formation vitro as well tumorigenicity vivo. Clinical data levels positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated involved deubiquitination EGLN3, a member 2-oxoglutarate iron-dependent dioxygenases. elicited tumor suppressor role preventing degradation Importantly, knockdown impaired USP9X-mediated suppression proliferation. regulated level apoptosis pathway genes de through thus cholangiocarcinoma. Conclusion These findings help understand alleviates malignant potential upregulation Consequently, provide novel insight into biomarker or serves therapeutic diagnostic target for