title: miR-409-3p inhibits HT1080 cell proliferation, vascularization and metastasis by targeting angiogenin.
abstract: Although the expression of angiogenin (ANG), an angiogenic and tumorigenic factor, is elevated in various types of cancers, its regulation mechanism remains unclear. In the present study, in silico search predicted that miR-409-3p targeted to the 3' untranslated region (3'UTR) of the ANG mRNA. Overexpression of miR-409-3p in fibrosarcoma HT1080 cells resulted in decreased steady-state level of ANG transcript and ANG production which were achieved through direct binding of this miRNA to the ANG 3'UTR. The suppressions of miR-409-3p to rRNA transcription, cell proliferation and vasculogenic mimicry could be partially restored by overexpression of ANG with a mutated binding site of miR-409-3p within the ANG 3'UTR. Ectopic expression of miR-409-3p in transplanted HT1080 cells led to the retardation of tumor growth, vascularization and lung metastasis in mouse tumor xenografts. In these xenografts tissues, the expression of miR-409-3p displayed an inverse correlation with ANG, which was also detected in human fibrosarcoma samples. In addition, the suppression effects of miR-409-3p on cell proliferation and angiogenesis in vitro were also found in human umbilical vein endothelial cells. Taken together, these data demonstrate that miR-409-3p inhibits tumor growth, vascularization and metastasis through down-regulating ANG expression.
authors.affiliation: Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Weng
authors.forename: Haojie
authors.initials: H
authors.lastname: Dong
authors.forename: Guangdi
authors.initials: G
authors.lastname: Chen
authors.forename: Yixing
authors.initials: Y
authors.lastname: Zhai
authors.forename: Rongpan
authors.initials: R
authors.lastname: Bai
authors.forename: Hu
authors.initials: H
authors.lastname: Hu
authors.forename: Linrong
authors.initials: L
authors.lastname: Lu
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000502:physiology*; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D012335:RNA, Ribosomal / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D017931:DNA Primers; C572367:MIRN409 microRNA, human; D035683:MicroRNAs; D012335:RNA, Ribosomal; C046366:angiogenin; D012259:Ribonuclease, Pancreatic