RBMS3通过抑制Wnt/β-catenin信号通路减弱胆囊癌细胞增殖、侵袭、迁移及血管形成的作用  

RBMS3 Inhibits Proliferation,Invasion,Migration,and Angiogenesis of Gallbladder Cancer Cells via Regulating Wnt/β-catenin Signaling Pathway

作　　者：张生彬[1] 王会雄 盛海涛 王俊杰[1] 云哲琳[1] Zhang Shengbing;Wang Huixiong;Sheng Haitao(Department of Hepatobiliary Surgery,Baogang Hospital,Baotou 014010,China)

机构地区：[1]内蒙古包钢医院肝胆外科,包头014010

出　　处：《华中科技大学学报（医学版）》2022年第5期618-624,共7页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：内蒙古自治区自然科学基金资助项目(No.2020MS08090)。

摘　　要：目的研究核糖核酸结合基序单链相互作用蛋白3(RBMS3)对胆囊癌细胞增殖、侵袭和迁移及血管形成的影响,并探讨其可能的分子作用机制。方法构建RBMS3过表达的胆囊癌细胞株;通过小干扰核糖核酸(siRNA)抑制胆囊癌细胞中Dickkopf1(DKK1)的表达;通过CCK-8法检测胆囊癌细胞增殖;通过侵袭小室(Transwell)实验检测细胞侵袭能力;通过划痕实验检测细胞迁移能力;采用小管形成实验检测血管形成能力;分别采用反转录聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)及蛋白免疫印迹(Western blot)检测基因mRNA和蛋白表达水平。结果过表达RBMS3的胆囊癌细胞增殖、侵袭、迁移及血管形成明显减少。与对照组比较,过表达RBMS3的胆囊癌细胞中Wnt/β-catenin信号通路相关蛋白β-catenin,c-Myc,细胞周期蛋白D1(Cyclin D1)表达明显降低,DKK1表达增加。同时转染DKK1干扰质粒和RBMS3过表达质粒到胆囊癌细胞中发现,抑制DKK1表达及过表达RBMS3对胆囊癌细胞增殖、侵袭、迁移以及血管形成有抑制作用。结论RBMS3可能通过抑制Wnt/β-catenin信号通路,抑制胆囊癌细胞的增殖、侵袭、迁移及血管形成。低表达的DKK1或可抑制RBMS3发挥抑癌作用。Objective To study the effect of ribonucleic acid-binding motif single-chain interacting protein 3(RBMS3)on the proliferation,invasion,migration and angiogenesis of gallbladder cancer cells,and to explore its possible molecular mechanism of action.Methods The RBMS3 overexpressed gallbladder cancer cell lines were constructed;the expression of Dickkopf1(DKK1)in gallbladder cancer cells was inhibited by small interfering ribonucleic acid(siRNA).The proliferation ability of gallbladder cancer cells was detected by CCK-8.Cell invasion was detected by transwell assay;cell migration was detected by scratch test;the angiogenesis ability was detected by tubule formation assay.Reverse transcription-polymerase chain reaction(RT-PCR)and Western blot were used to detect mRNA and protein expression levels of gene.Results The proliferation,invasion,migration and angiogenesis of gallbladder cancer cells were significantly reduced with overexpression of RBMS3.Compared with the control group,the expression levels of Wnt/β-catenin signaling pathway related proteinsβ-catenin,c-Myc and Cyclin D1 in gallbladder cancer cells were significantly decreased in gallbladder cancer cells with overexpression of RBMS3,and the expression of DKK1 was increased.After transfection of DKK1 interference plasmid and RBMS3 overexpression plasmid into gallbladder cancer cells,it could be found that the inhibition of DKK1 expression and overexpression of RBMS3 had an inhibitive effect on the proliferation,invasion,migration and angiogenesis of gallbladder cancer cells.Conclusion RBMS3 may inhibit the proliferation,invasion,migration and angiogenesis of gallbladder cancer cells by inhibiting Wnt/β-catenin signaling pathway.Low expression of DKK1 can inhibit tumor suppressor effect of RBMS3 in gallbladder cancer,and the relationship between DKK1 and RBMS3 calls for further investigation.

关 键 词：RBMS3 WNT/Β-CATENIN 胆囊癌 增殖 侵袭 迁移 

分 类 号：R735.8[医药卫生—肿瘤]