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MiR-629-5p promotes the invasion of lung adenocarcinoma via increasing both tumor cell invasion and endothelial cell permeability

文献类型：期刊论文

作者Li, Yu3,4; Zhang, Huibiao5; Fan, Lei3,4; Mou, Jiahui3,4; Yin, Yue6; Peng, Chao7; Chen, Yuxiang4; Lu, Henglei2,4; Zhao, Liting8; Tao, Zhouteng3,4
刊名ONCOGENE
出版日期2020-02-27
页码16
ISSN号0950-9232
DOI10.1038/s41388-020-1228-1
通讯作者Huang, Ruimin(rmhuang@simm.ac.cn) ; Ren, Jin(jren@cdser.simm.ac.cn)
英文摘要Tumor invasion underlies further metastasis, the leading cause for cancer-related deaths. Deregulation of microRNAs has been identified associated with the malignant behavior of various cancers, including lung adenocarcinoma (LUAD), the major subtype of lung cancer. Here, we showed the significantly positive correlation between miR-629-5p level and tumor invasion in LUAD specimens (n = 49). In a human LUAD metastasis mouse model, H1650 cells (high level of miR-629-5p) were more aggressive than A549 cells (low level of miR-629-5p) in vivo, including higher incidence of vascular invasion and pulmonary colonization. Ectopic expression of miR-629-5p in A549 cells also increased their invasive capability. Then we identified that miR-629-5p promotes LUAD invasion in a mode of dual regulation via tumor cells invasion and endothelial cells permeability, respectively. In tumor cells, miR-629-5p enhanced motility and invasiveness of tumor cells by directly targeting PPWD1 (a cyclophilin), which clinically related to tumor invasion in LUAD specimens. Restoring PPWD1 protein significantly attenuated the invasion-promoting effects of miR-629-5p. Besides, exosomal-miR-629-5p secreted from tumor cells could be transferred to endothelial cells and increased endothelial monolayers permeability by suppressing CELSR1 (a nonclassic-type cadherin), which had a low level in the endothelial cells of invasive LUAD specimens. Activating the expression of CELSR1 in endothelial cells markedly blocked the effect of miR-629-5p. Our study suggests the dual roles of miR-629-5p in tumor cells and endothelial cells for LUAD invasion, implying a therapeutic option to targeting miR-629-5p using the "one stone, two birds" strategy in LUAD.
WOS关键词UP-REGULATION ; CANCER ; METASTASIS ; EXPRESSION ; TARGETS ; GROWTH ; CELSR1 ; ANGIOGENESIS ; SUPPRESSES ; MIGRATION
资助项目National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09101001-003-007] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-010-001] ; National Natural Science Foundation of china[91859106] ; One Hundred Talent Program of Chinese Academy of Sciences ; State Key Laboratory of Drug Research ; Shanghai Committee of Science and Technology, China[18DZ2290200]
WOS研究方向Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
语种英语
WOS记录号WOS:000516891300003
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/281267]  
专题新药研究国家重点实验室
通讯作者Huang, Ruimin; Ren, Jin
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Shanghai Univ Chinese Med, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Fudan Univ, Huadong Hosp, Dept Thorac Surg, Shanghai 200040, Peoples R China
6.Natl Facil Prot Sci Shanghai, Zhangjiang Lab, Shanghai 201210, Peoples R China
7.Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai 201204, Peoples R China
8.Fudan Univ, Huadong Hosp, Dept Nursing, Shanghai 200040, Peoples R China
9.Beijing Inst Basic Med Sci, Brain Sci Ctr, Beijing 100730, Peoples R China
推荐引用方式
GB/T 7714		 Li, Yu,Zhang, Huibiao,Fan, Lei,et al. MiR-629-5p promotes the invasion of lung adenocarcinoma via increasing both tumor cell invasion and endothelial cell permeability[J]. ONCOGENE,2020:16.
APA Li, Yu.,Zhang, Huibiao.,Fan, Lei.,Mou, Jiahui.,Yin, Yue.,...&Ren, Jin.(2020).MiR-629-5p promotes the invasion of lung adenocarcinoma via increasing both tumor cell invasion and endothelial cell permeability.ONCOGENE,16.
MLA Li, Yu,et al."MiR-629-5p promotes the invasion of lung adenocarcinoma via increasing both tumor cell invasion and endothelial cell permeability".ONCOGENE (2020):16.

入库方式： OAI收割

来源：上海药物研究所

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