Experimental Study Of NUSAP1 Promoting Pancreatic Adenocarcinoma Growth And Paclitaxel Resistance By Upregulating Homologous Recombination Repair Pathway

Objective: Pancreatic adenocarcinoma chemotherapy is ineffective,and the mechanism of resistance to paclitaxel is unclear.This study aimed to explore the role and mechanism of NUSAP1 in pancreatic adenocarcinoma growth and paclitaxel resistance,and to clarify its clinical value.Methods: The expression of NUSAP1 in pancreatic adenocarcinoma tissues and normal tissues in public databases was analyzed,and validated by IHC and WB.Cox regression and Kaplan-Meier survival analysis were performed on the clinicopathological data.The relationship between the expression of NUSAP1 in pancreatic adenocarcinoma cells and the IC50 value of paclitaxel was analyzed and verified.The effects of NUSAP1 on the growth of pancreatic adenocarcinoma cells and its role in paclitaxel resistance were analyzed by RTCA,CDX model and Annexin V/PI,and potential mechanisms were sought and verified.Results: Public database analysis,IHC and WB results showed that the expression of NUSAP1 in pancreatic adenocarcinoma tissues was higher than that in normal tissues.Analysis of clinicopathological data showed that high expression of NUSAP1 was an independent risk factor for OS（P < 0.01）,and patients with high expression of NUSAP1 had shorter OS（P < 0.01）,higher clinical stage（P < 0.05）,and lower degree of tissue differentiation（P < 0.01）.Bioinformatics analysis showed that NUSAP1 expression was positively correlated with paclitaxel IC50 value in pancreatic adenocarcinoma cell lines.After knockout of NUSAP1,the IC50 value of paclitaxel decreased,the proliferation ability in vitro and in vivo decreased,and the sensitivity to paclitaxel treatment increased.Preliminary mechanism studies showed that NUSAP1 expression was associated with the homologous recombination repair pathway in pancreatic adenocarcinoma,and RAD51 expression was decreased after NUSAP1 was knocked out.Conclusions: NUSAP1 may promote the growth of pancreatic adenocarcinoma and induce paclitaxel resistance by upregulating the homologous recombination repair pathway,which deserves further study.