title: MiR-93 enhances angiogenesis and metastasis by targeting LATS2.
abstract: Here we report that miR-93, a miRNA in the miR-106B~25 cluster, a paralog of the miR-17-92 cluster, was significantly upregulated in human breast carcinoma tissues. We stably expressed miR-93 in the MT-1 human breast carcinoma cell line and found that tumors formed by the miR-93 cells contained more blood vessels than those formed by the control cells. Co-culture experiments indicated that the MT-1 cells displayed a high activity of adhesion with endothelial cells and could form larger and more tube-like structures with endothelial cells. Lung metastasis assays were performed in a mouse metastatic model, and it was found that expression of miR-93 promoted tumor cell metastasis to lung tissue. In cell culture, expression of miR-93 enhanced cell survival and invasion. We examined the potential target that mediated miR-93's effects and found that the large tumor suppressor, homology 2 (LATS2) was a target of miR-93. Higher levels of LATS2 were associated with cell death in the tumor mass. Silencing LATS2 expression promoted cell survival, tube formation and invasion, while ectopic expression of LATS2 decreased cell survival and invasion. These findings demonstrated that miR-93 promoted tumor angiogenesis and metastasis by suppressing LATS2 expression. Our results suggest that the inhibition of miR-93 function may be a feasible approach to repress tumor metastasis.
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON Canada.
authors.forename: Ling
authors.initials: L
authors.lastname: Fang
authors.forename: William W
authors.initials: WW
authors.lastname: Du
authors.forename: Weining
authors.initials: W
authors.lastname: Yang
authors.forename: Zina Jeyapalan
authors.initials: ZJ
authors.lastname: Rutnam
authors.forename: Chun
authors.initials: C
authors.lastname: Peng
authors.forename: Haoran
authors.initials: H
authors.lastname: Li
authors.forename: Yunxia Q
authors.initials: YQ
authors.lastname: O'Malley
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Askeland
authors.forename: Sonia
authors.initials: S
authors.lastname: Sugg
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Tanvi
authors.initials: T
authors.lastname: Mehta
authors.forename: Zhaoqun
authors.initials: Z
authors.lastname: Deng
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D018920:Coculture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C543350:MIRN93 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases