Role of hepatocyte nuclear factor 4 alpha in cell proliferation and gemcitabine resistance in pancreatic adenocarcinoma

摘要: Hepatocyte nuclear factor 4α (HNF4α) is a tissue-specific transcription that regulates the expression of numerous genes in hepatocytes and pancreatic β cells. HNF4α has been reported to affect cell proliferation chemoresistance several cancers. However, role adenocarcinoma (PDAC) not studied extensively remains unclear. By utilizing immunohistochemical (IHC) staining, we measured PDAC tissues. silencing lines, assessed impact on cancer gemcitabine sensitivity. We used CCK8 colony formation assays examine effect proliferation. A flow cytometry assay was assess apoptosis. The gemcitabine-related detected by quantitative real‑time PCR (qRT-PCR) Western blotting. IHC utilized correlation between human equilibrative nucleoside transporter 1 (hENT1) patients. Chromatin immunoprecipitation (ChIP) dual‑luciferase reporter were confirm hENT1 target gene HNF4α. Increased tissues; patients with higher displayed worse prognosis. To elucidate function HNF4α, examined its proliferation, apoptosis resistance. In HNF4α-silenced Capan-1 MiaPaCa-2 cells, observed decreased increased sensitivity compared those controls. mechanism chemosensitivity then explored. response silencing, levels proteins, deoxycytidine kinase (dCK) significantly increased. Additionally, negatively correlated tissue samples. Moreover, identified as downstream prognostic marker for overall survival, required promotes resistance downregulating hENT1. Therefore, targeting might reverse provide novel treatment strategies PDAC.