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Abstract: Objectives: Thymidine kinase 1 (TK1) is one of the salvage enzymes engaged in the synthesis of DNA. Although a pro‐carcinogenetic role of TK1 has been reported in various types of cancers, its role in pancreatic ductal adenocarcinoma (PDAC) is still unknown. The study is aimed to elaborate the function of TK1 in PDAC and the potential mechanisms in the following study. Materials and methods: TK1 expression was analysed by immunohistochemistry, real‐time PCR and Western blot, and its relationship with clinicopathological characteristics of PDAC patients was further investigated. To verify the function of TK1 and potential mechanism, TK1 siRNA was used to transfect PDAC cells and performed a series of assays in cell and animal models. Results: The level of TK1 expression was higher in cancerous tissues compared with matched adjacent tissues. TK1 overexpression was associated with progression of PDAC and poor prognosis. Knockdown of TK1 could suppress cell proliferation via inducing S phase arrest mediated by upregulation of P21. Further mechanism investigation suggested that transcription factor E2F‐1 could directly regulate the TK1 and promote tumour proliferation. Conclusions: The results suggested that TK1 might be involved in the development and progression of PDAC by regulating cell proliferation and show that TK1 may work as a promising therapeutic target in patients with PDAC. [ABSTRACT FROM AUTHOR]

Cell proliferation ability was examined in the Blank, inhibitor-NC, PLL 3.7, miR-23a and inhibitor groups after (A) 24 h and (B) 48 h treatment. Effects of miR-23a on proliferation and metastasis ability of pancreatic cancer cells. [Extracted from the article]

• Expression of some GRGs was significantly associated with the prognosis or progression of pancreatic cancer. • Pancreatic cancer cell death was enhanced following inhibition of glycolysis. • The sensitivity of cancer cells to GEM was elevated by 2-DG. • A prognostic model involving GRGs should be helpful for pancreatic cancer early diagnosis and treatment. Previous studies have reported that increased glycolytic activity enhances chemotherapy resistance in some types of malignancies. However, whether glycolysis influences the curative effect of gemcitabine (GEM) on pancreatic cancer (PC) cells remains unclear. The aim of this study was to investigate the status of glycolysis in PC and its association with tolerance to GEM. Data from The Cancer Genome Atlas (TCGA) were used to analyze the correlation between glycolysis-related gene (GRG) expression and PC progression and prognosis. 2-Deoxy-D-glucose (2-DG) was applied to assess the effect of glycolysis inhibition on PC cell death and GEM tolerance. Expression of some GRGs, such as HK1, GAPDH, PKM2, and LDHA, was significantly associated with the prognosis of PC. Furthermore, HK1, PKLR, and LDHA expression correlated positively with PC progression. Further analysis revealed that cancer cell death was markedly enhanced following glycolysis inhibition and that the sensitivity of cancer cells to GEM was notably increased in the presence of 2-DG. Our findings indicate that abnormally increased glycolytic activity promotes the development of PC and enhances drug tolerance to GEM. 2-DG combined with GEM is a potential therapy for PC. [ABSTRACT FROM AUTHOR]