首页|A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Human-specific insertions play important roles in human phenotypes and diseases.Here we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5.Interestingly,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chim-panzee divergence.We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques.In addition,over-expression TBC1D8B promoted cell pro-liferation and migration through"a dual finger"catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo.Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells.Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene.These findings provide a significant insight into the effects of human-specific insertions on evolution.

human-specific insertionenhancergene expressioncell proliferation and migration

Hui Zhao、Lin-Lin Liu、Jian Sun、Lian Jin、Hai-Bing Xie、Jian-Bo Li、Hui Xu、Dong-Dong Wu、Xiao-Lin Zhuang、Min-Sheng Peng、Ya-Jun Guo、Wei-Zhu Qian、Newton O.Otecko、Wei-Jie Sun、Liang-Hu Qu、Jie He、Zhao-Li Chen、Rong Liu、Ce-Shi Chen、Ya-Ping Zhang

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State Key Laboratory for Conservation and Utilization of Bio-resource,School of Life Sciences,School of Ecology and Environmental Science,Yunnan University,Kunming 650091,China

School of Forensic Medicine,Kunming Medical University,Kunming 650500,China

The Third Affiliated Hospital,Kunming Medical University,Kunming 650118,China

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650201,China

State Key Laboratory of Genetic Resources and Evolution,Yunnan Laboratory of Molecular Biology of Domestic Animals,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650201,China

The Key Laboratory of Gene Engineering of the Ministry of Education,State Key Laboratory for Biocontrol,Sun Yat-sen University,Guangzhou 510275,China

National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering and Antibody,Shanghai 201203,China

Department of Thoracic Surgery,Cancer Institute and Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China

Academy of Biomedical Engineering,Kunming Medical University,Kunming 650500,China

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Key Research and Development Program of Yunnan国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家重点研发计划国家重点研发计划国家重点研发计划Spring City Plan:the High-level Talent Promotion and Training Project of KunmingYunnan Fundamental Research ProjectsYunnan Fundamental Research Projectsopen project of State Key Laboratory of Genetic Resources and Evolution,Kunming Institute of Zoology,Chinese Academy of ScieYunnan University's new round of"Double First-Class"Construction Project—For People's Life and Health

202203AC100010317603113216023681830087U21022032022YFC26016042018YFC20004002020YFA01123002022SCP001CY22624104202101AS070050GREKF17-01CY22624104

2024

10.1007/s11427-023-2442-3

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(4)
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