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Ding Li,1,* Xiao-Feng Ni,1,* Hengjie Tang,1,* Jiecheng Zhang,1 Chenlei Zheng,1 Jianhu Lin,1 Cheng Wang,1 Linxiao Sun,1 Bicheng Chen1,2 1Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bicheng Chen; Linxiao Sun Email chenbicheng@hotmail.com; sunlinxiao@wmu.edu.cnBackground: Pancreatic cancer (PC) is one of the most well-known malignancies with high mortality, but the underlying mechanism of PC remains unknown. Keratin17 (KRT17) expression has been reported in many malignancies, but its functions in PC are not clear. The aim of our study was to evaluate KRT17 expression and its potential role in PC.Methods: The online databases GEPIA and THPA were used to identify KRT17 expression in tissues. Quantitative real-time PCR (qRT-PCR) was used to determine KRT17 expression in cell lines. Ki67 and ROS levels were detected by immunofluorescence assay and a 2ʹ,7ʹ-dichlorodihydrofluorescein diacetate (DCFH-DA) probe. KRT17 downregulation was induced by the small interfering RNA (siRNA) technique. Proliferation function was evaluated by colony formation assay and RTCA. Migration and invasion were evaluated by transwell migration assay. A Western blot assay was used to detect protein levels.Results: KRT17 was overexpressed in PC tissues compared to that in normal tissues. The results showed that Ki67 and ROS levels were decreased in pancreatic cancer cells after transfection with siKRT17. After KRT17 downregulation in PC cell lines, cell viability functions, including proliferation, migration and invasion, and mTOR/S6K1 phosphorylation levels were attenuated.Conclusion: KRT17 knockdown significantly inhibited proliferation, migration and invasion in pancreatic cancer cells.Keywords: KRT17, knockdown, proliferation, migration, invasion, pancreatic cancer, mTOR/S6K1

Fubiao Ni,1,* Hengjie Tang,1,* Cheng Wang,1,* Hewei Zhang,1 Chenlei Zheng,1 Ning Zhang,2 Bicheng Chen,1 Linxiao Sun1 1Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 2First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linxiao Sun; Bicheng Chen Email sunlinxiao@wmu.edu.cn; bichengchen@hotmail.comBackground: Although the incidence of pancreatic cancer has increased markedly, the 5-year survival rate for this disease is considerably low compared with other types of cancer. Moreover, the mortality rate of pancreatic cancer is similar to its incidence rate. Current therapeutic agents exhibit a lack of specificity for pancreatic cancer. Baohuoside I is traditionally used to treat orgasmic disorder and inflammation. However, its role in pancreatic cancer is unknown.Objective: To explore the effects of Baohuoside I on pancreatic cancer and to study the potential-related molecular mechanism.Materials and methods: In the present study, the antineoplastic effect of Baohuoside I was investigated with regard to pancreatic cancer via colony formation, transwell and migration assay. The energy metabolism changes of pancreatic cancer were tested by flow cytometry analysis and oxidative phosphorylation and glycolysis assay. The target signaling members were analyzed by Western blot.Results: Baohuoside I inhibited the cell growth of pancreatic cancer cells. In addition, it affected intracellular energy metabolism to induce cancer cell apoptosis via the mTOR/S6K1 and the caspase/Bcl2/Bax signaling pathways.Conclusion: The present data provide further insight into the development of novel drugs against pancreatic cancer.Keywords: Baohuoside I, pancreatic cancer, apoptosis

Fubiao Ni,1,* Hengjie Tang,1,* Cheng Wang,1,* Zixiang Wang,2 Fangyi Yu,2 Bicheng Chen,1 Linxiao Sun1 1Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2First College of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linxiao SunKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, First Affiliated Hospital of Wenzhou MedicalUniversity, Fanhai West Road, Nanbaixiang Street, Wenzhou 325006, Zhejiang, People’s Republic of ChinaEmail sunlinxiao@wmu.edu.cnnBackground: Current investigations suggest that the Base Excision Repair (BER) system may change DNA repair capacity and affect clinical gastric cancer progression such as overall survival. However, the prognostic value of BER system members in gastric cancer remains unclear.Methods: We explored the prognostic correlation between 7 individual BER genes, including uracil-DNA glycosylase (UNG), Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), Methyl-CpG binding domain 4 (MBD4), thymine DNA glycosylase (TDG), 8-oxoguanine DNA glycosylase (OGG1), MutY DNA glycosylase (MUTYH) and Nei like DNA glycosylase 1 (NEIL1), expression and overall survival (OS) in different clinical data, such as Lauren classification, pathological stages, human epidermal growth factor receptor-2 (HER2) expression status, treatment strategy, gender and differentiation degree in gastric cancer patients, using Kaplan-Meier plotter (KM plotter) online database. Based on the bioinformatics analysis, we utilized Berzosertib (VE-822) to inhibit DNA damage repair in cancer cells compared to solvent control group via real-time cellular analysis (RTCA), flow cytometry, colony formation and migration assay. Finally, we utilized reverse transcription-polymerase chain reaction (RT-PCR) to confirm the expression of BER members between normal and two gastric cancer cells or solvent and VE-822 treated groups.Results: Our work revealed that high UNG mRNA expression was correlated with high overall survival probability; however, high SMUG1, MBD4, TDG, OGG1, MUTYH and NEIL1 mRNA expression showed relatively low overall survival probability in all GC patients. Additionally, UNG was associated with high overall survival probability in intestinal and diffuse types, but SMUG1 and NEIL1 showed opposite results. Further, VE-822 pharmacological experiment suggested that inhibition of DNA damage repair suppressed gastric cancer cells’ proliferation and migration ability via inducing apoptosis. Further, real-time polymerase chain reaction results proposed the inhibition of gastric cancer cells by VE-822 may be through UNG, MUTYH and OGG-1 of BER system.Conclusion: We comprehensively analyze the prognostic value of the BER system (UNG, SMUG1, MBD4, TDG, OGG1, MUTYH and NEIL1) based on bioinformatics analysis and experimental confirmation. BER members are associated with distinctive prognostic significance and maybe new valuable prognostic indicators in gastric cancer.Keywords: base excision repair, gastric cancer, Kaplan-Meier plotter