LSM12 facilitates the progression of colorectal cancer by activating the WNT/CTNNB1 signaling pathway

作     者：YAN ZHUANG CHUNLAN NING PENGFEI LIU YANPENG ZHAO YUE LI ZHENCHI MA LULING SHAN YINGZHE PIAO PENG ZHAO XUN JIN 

作者机构：Department of Colorectal OncologyTianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin300060China Department of Biochemistry and Molecular BiologyTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin300060China Tianjin Medical UniversityTianjin300070China Department of OncologyTianjin Academy of Traditional Chinese Medicine Affiliated HospitalTianjin300120China Tianjin Marvel Medical LaboratoryTianjin Marvelbio Technology Co.Ltd.Tianjin300381China Department of Gastro Colorectal OncologyTianjin Cancer Hospital Airport HospitalTianjin300304China Department of Neuro-Oncology and NeurosurgeryTianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy TianjinTianjin’s Clinical Research Center for CancerTianjin300060China 

出 版 物：《Oncology Research》 (肿瘤学研究（英文）)

年 卷 期：2022年第30卷第6期

页      面：289-300页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the Science and Technology Support Plan Key Projects of Tianjin(Grant No.20YFZCSY00070) the National Natural Science Foundation of China(Grant Nos.82073276,82273100) the China Digestive Tumor Clinical Scientific Research Public Welfare Project(Grant No.P014-058) Science and Technology project of Health Commission of Tianjin Binhai New Area(Grant No.2022BWKY016). 

主　　题：CRC LSM12 WNT CTNNB1 Apotosis 

摘      要：Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway.Here,we found that LSM12 is highly expressed in CRC patient-derived tissues and cells.LSM12 is involved in the proliferation,invasion,and apoptosis of CRC cells,similar to the function of WNT signaling in CRC.Furthermore,protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1(also known asβ-Catenin)and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway.LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis.Taken together,we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation,and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.