Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer malignant behaviors by activation of target of rapamycin kinase/autophagy signaling  

作　　者：Juan Sun Jin-Xiu Zhang Meng-Shi Li Meng-Bin Qin Ruo-Xi Cheng Qing-Ru Wu Qiu-Ling Chen Dan Yang Cun Liao Shi-Quan Liu Jie-An Huang 

机构地区：[1]Department of Gastroenterology,The Second Affiliated Hospital of Guangxi Medical University,Nanning 530007,Guangxi Zhuang Autonomous Region,China [2]Department of Colorectal&Anal Surgery,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi Zhuang Autonomous Region,China

出　　处：《World Journal of Gastroenterology》2024年第26期3229-3246,共18页世界胃肠病学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China,No.81760516;Natural Science Foundation of Guangxi,China,No.2019GXNSFAA185030;Self-Financed Scientific Research Projects of Guangxi Zhuang Autonomous Region Health and Family Planning Commission,China,No.Z20181003;Guangxi Medical University Youth Science Fund Project,China,No.GXMUYSF202221.

摘　　要：BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

关 键 词：Colorectal cancer Monopolar spindle-binding protein 3B Mechanistic target of rapamycin kinase AUTOPHAGY Prognosis 

分 类 号：R73[医药卫生—肿瘤]