Resistance to ferroptosis, a form of regulated cell death caused by disruptions in iron ion and intracellular redox homeostasis, is closely related to tumorigenesis and tumor drug resistance; therefore, targeting ferroptosis-related pathways has garnered attention as a potential antitumor therapeutic strategy. However, the molecular mechanisms underlying ferroptosis resistance in tumor cells remain unknown. Zinc-finger estrogen receptor interaction clone 6 (ZER6) consists of two isoforms with distinct N-termini, p52-ZER6 and p71-ZER6. ZER6 is upregulated in tumors and promotes tumorigenic potential; however, whether ZER6 is involved in tumor cell ferroptosis resistance remains unknown. Herein, we identified p52-ZER6 as a novel regulator of tumor cell ferroptosis resistance. p52-ZER6 promotes the transcriptional activity of DAZAP1, an RNA-binding protein. DAZAP1, in turn, enhances the stability of SLC7A11 mRNA by binding to its 3'-UTR region, thereby increasing SLC7A11 expression and cellular glutathione levels. This subsequently reduces lipid peroxide accumulation and enhances tumor cell ferroptosis resistance, eventually promoting tumorigenic potential. These findings reveal a new function of p52-ZER6 in regulating SLC7A11 mRNA stability via DAZAP1, ultimately leading to ferroptosis resistance and tumorigenic potential. Additionally, we also suggest targeting p52-ZER6 as a potential strategy to promote the efficacy of ferroptosis-based antitumor therapies.

Objective:To explore the feasibility and safety of laparoscopic radical gastrectomy for gastric cancer through analysising the laparoscopic radical gastrectomy and open radical gastrectomy.Methods:Retrieval the Cochrane Library,PubMed,EMBASE,CBM,VIP,CNKI,WANFANG DATA,the time is from January 2010 to August 2015.Bring into the comparative studies about laparosopic radical gastrectomy and laparotomye.Processing data using the revman 5.2 to reaserch the feasibility and safety of laparoscopic radical gastrectomy.Results:7 clinical comparative studies were included in this study.The observation group was the group of laparoscopic radical gastrectomy and the control group was the group of laparotomye.Results showed that the length of incision of the observation group was shorter[MD=-12.93,95％ CI (-13.16,-12.70),P＜0.00001];The observation group bleeding was lesser[MD=-129.98,95％C1(-220.54,-39.42),P=0.005];The number of lymph node of the two groups had no significant difference [MD=0.77,95％ CI (-2.56,3.60),P=0.56];The operation time of the observation group was longer [MD=49.17,95％ CI (25.32,73.02),P＜0.0001];The hospitalization time of the observation group is shorter [MD=-2.27,95％ CI (-3.77,0.77),P=0.003].Conclusion:Laparoscopic radical gastrectomy is feasible and it is superior to laparotomye within the thoroughness,minimally invasiving and safety.