A controlled random gene perturbation method identifies ARPC1B gene as a key regulator of cancer metastasis  

作　　者：De Chang Hongzhen Du Xiaowei Chen Xiaocui Bian Wenjia Tian Jing Shen Yiju Wei Yunpeng Jiang Charles Dela Cruz Lixin Xie Lokesh Sharma Kailong Li 

机构地区：[1]College of Pulmonary and Critical Care Medicine,Chinese PLA General Hospital,Beijing 100083,China [2]Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing 100005,China [3]Section of Pulmonary and Critical Care and Sleep Medicine,Department of Medicine,Yale University School of Medicine,New Haven,CT 06520,USA [4]Department of Biochemistry and Biophysics,Peking University Health Science Center,Beijing 100191,China

出　　处：《Genes & Diseases》2023年第3期687-689,共3页基因与疾病（英文）

基　　金：This study was supported by funding from The National Key Research and Development Program of China(No.2021YFC2302300);Beijing Nova Program Interdisciplinary Cooperation Project(DC;No.Z191100001119021);Chinese PLA General Hospital Youth Project(DC;No.QNF19074);Beijing Nova Program Project(DC;No.Z171100001117012);China 13th Five-year National Key Grant(LXX,No.2018ZX09201013);the Fundamental Research Funds for the Central Universities(KL;No.BMU2021YJ073).

摘　　要：The discovery of clinically useful targets to treat specific pathological conditions can provide novel therapeutic approaches.To unbiasedly identify key genes related to tumor metastasis,we developed a random gene perturbation method using a piggyBac transposon system under the control of a doxycycline regulated promoter.Using this random gene perturbation method and utilizing a mouse model of metastatic pancreatic cancer,we identified genes dysregulated in metastasized cells from a random mutagenesis library after multiple rounds of in vivo selection.Analysis of these metastasized clones revealed the downregulation of ARPC1B gene.Our further mechanistic studies revealed that ARPC1B gene and its closely related gene ARPC1A worked in a regulatory loop to control tumor metastasis.These findings validate that piggyBac transposon mediated random gene perturbation is a powerful tool to investigate the functional relevance of novel genes and the ARPC1A/B axis is a potential key regulator of tumor metastasis.

关 键 词：METASTASIS cancer RANDOM 

分 类 号：R730.2[医药卫生—肿瘤]