title: RNAi-mediated silencing of AQP1 expression inhibited the proliferation, invasion and tumorigenesis of osteosarcoma cells.
abstract: Aquaporin 1 (AQP1), a member of water channel proteins, functions as a water-selective transporting protein in cell membranes. In recent years, AQP1 has been found to be overexpressed in various tumors. However, the molecular mechanism underlying the biological function of AQP1 in osteosarcoma is still unclear. This study was aimed at elucidating the roles of AQP1 in regulating the biological behavior of osteosarcoma cells. In this study, we found that AQP1 mRNA was elevated in osteosarcoma tissue. High level of AQP1 was associated with poor prognosis in osteosarcoma. Then, we found that knockdown of AQP1 in osteosarcoma cells, U2OS or MG63 cells inhibited cell proliferation and significantly increased cells population in G1 phase. Additionally, suppressing AQP1 expression in osteosarcoma cells dramatically induced cell apoptosis. We also found that down-regulation of AQP1 significantly inhibited cell adhesion and invasion. More importantly, AQP1 knockdown inhibited tumor growth in vivo and prolonged the survival time of nude mice. Gene set enrichment analysis (GSEA) showed that transforming growth factor-β (TGF-β) signaling pathway and focal adhesion genes was correlatively with AQP1 expression. In addition, real time PCR and western blot analysis revealed that expression of TGF-β1/TGF-β2, RhoA and laminin β 2 (LAMB2) was remarkably impaired by AQP1 silencing. In conclusion, AQP1 may be a useful diagnosis and prognosis marker for osteosarcoma. AQP1 knockdown can effectively inhibit cell proliferation, adhesion, invasion and tumorigenesis by targeting TGF-β signaling pathway and focal adhesion genes, which may serve a promising therapeutic strategy for osteosarcoma.
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wu
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Shi
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Luo
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Qian
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Huang
authors.affiliation: a Department of Orthopedics ; Shanghai Tenth People's Hospital; Tongji University School of Medicine ; Shanghai , PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics* / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059585:G1 Phase Cell Cycle Checkpoints; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D034622:RNA Interference; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C496020:AQP1 protein, human; D016212:Transforming Growth Factor beta; D051398:Aquaporin 1
keywords: AQP1; RhoA; TGF; apoptosis; invasion-β; osteosarcoma; proliferation