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

doi:10.1038/s41388-020-1228-1

	MiR-629-5p promotes the invasion of lung adenocarcinoma via increasing both tumor cell invasion and endothelial cell permeability
	Li, Yu 1,2; Zhang, Huibiao 3; Fan, Lei 1,2; Mou, Jiahui 1,2; Yin, Yue 4; Peng, Chao 5; Chen, Yuxiang 1; Lu, Henglei 1,6; Zhao, Liting 7; Tao, Zhouteng 1,2
刊名	ONCOGENE
	2020-02-27
页码	16
ISSN号	0950-9232
DOI	10.1038/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.
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关键词	UP-REGULATION ; CANCER ; METASTASIS ; EXPRESSION ; TARGETS ; GROWTH ; CELSR1 ; ANGIOGENESIS ; SUPPRESSES ; MIGRATION
WOS研究方向	Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000516891300003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281267]
专题	中国科学院上海药物研究所
通讯作者	Huang, Ruimin; Ren, Jin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Fudan Univ, Huadong Hosp, Dept Thorac Surg, Shanghai 200040, Peoples R China 4.Natl Facil Prot Sci Shanghai, Zhangjiang Lab, Shanghai 201210, Peoples R China 5.Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai 201204, Peoples R China 6.Shanghai Univ Chinese Med, Shanghai 201203, Peoples R China 7.Fudan Univ, Huadong Hosp, Dept Nursing, Shanghai 200040, Peoples R China 8.Beijing Inst Basic Med Sci, Brain Sci Ctr, Beijing 100730, Peoples R China 9.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, 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.