RNA-binding protein CPSF6 regulates IBSP to affect pyroptosis in gastric cancer  

作　　者：Xue-Jun Wang Yong Liu Bin Ke Li Zhang Han Liang 

机构地区：[1]Department of Gastric Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin’s Clinical Research Center for Cancer,Tianjin Key Laboratory of Digestive Cancer,Tianjin 300060,China

出　　处：《World Journal of Gastrointestinal Oncology》2023年第9期1531-1543,共13页世界胃肠肿瘤学杂志（英文版）（电子版）

摘　　要：BACKGROUND Extensive evidence has illustrated the promotive role of integrin binding sialoprotein(IBSP)in the progression of multiple cancers.However,little is known about the functions of IBSP in gastric cancer(GC)progression.AIM To investigate the mechanism underlying the regulatory effects of IBSP in GC progression,and the relationship between IBSP and cleavage and polyadenylation factor 6(CPSF6)in this process.METHODS The mRNA and protein expression of relevant genes were assessed through realtime quantitative polymerase chain reaction and Western blot,respectively.Cell viability was evaluated by Cell Counting Kit-8 assay.Cell invasion and migration were evaluated by Transwell assay.Pyroptosis was measured by flow cytometry.The binding between CPSF6 and IBSP was confirmed by luciferase reporter and RNA immunoprecipitation(RIP)assays.RESULTS IBSP exhibited higher expression in GC tissues and cell lines than in normal tissues and cell lines.IBSP knockdown suppressed cell proliferation,migration,and invasion but facilitated pyroptosis.In the exploration of the regulatory mechanism of IBSP,potential RNA binding proteins for IBSP were screened with catRAPID omics v2.0.The RNA-binding protein CPSF6 was selected due to its higher expression in stomach adenocarcinoma.Luciferase reporter and RIP assays revealed that CPSF6 binds to the 3’-untranslated region of IBSP and regulates its expression.Knockdown of CPSF6 inhibited cell proliferation,migration,and invasion but boosted pyroptosis.Through rescue assays,it was uncovered that the retarded GC progression mediated by CPSF6 knockdown was reversed by IBSP overexpression.CONCLUSION Our study highlighted the vital role of the CPSF6/IBSP axis in GC,suggesting that IBSP might be an effective biotarget for GC treatment.

关 键 词：Integrin binding sialoprotein Cleavage and polyadenylation factor 6 PYROPTOSIS Gastric cancer 

分 类 号：R730.5[医药卫生—肿瘤]