title: Cell-derived microvesicles mediate the delivery of miR-29a/c to suppress angiogenesis in gastric carcinoma.
abstract: Microvesicles (MVs) secreted from cells have been found to mediate signal transduction between cells. In the tumor microenvironment, VEGF released from cancer cells plays a key role in promoting tumor angiogenesis. In this study, we characterized the inhibitory effect of MV-delivered miR-29a/c on angiogenesis and tumor growth in gastric cancer (GC). We found that the downregulation of miR-29a/c increases VEGF expression and release in GC cells, promoting the growth of vascular cells. By simulating the tumor microenvironment, the MV-delivered miR-29a/c significantly suppresses VEGF expression in GC cells, inhibiting vascular cell growth, metastasis, and tube formation. We also used a tumor implantation mouse model to show that secreted MVs containing overexpressed miR-29a/c significantly reduced the growth rate of the vasculature and tumors in vivo. To conclude, our results contribute to a novel anti-cancer strategy using miRNA-containing MVs to control tumor cell growth by blocking angiogenesis.
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Bai
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Deng
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Duan
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ning
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Ge
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Likun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: dingzhih72@163.com.
authors.forename: Dingzhi
authors.initials: D
authors.lastname: Huang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: yingguoguang163@163.com.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Ying
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: bayi@tjmuch.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ba
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D055252:Cell-Derived Microparticles / Q000235:genetics; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000628:therapy; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Gastric cancer; Microvesicle; VEGF; miR-29