title: RLN2 Is a Positive Regulator of AKT-2-Induced Gene Expression Required for Osteosarcoma Cells Invasion and Chemoresistance.
abstract: The aim of the study was to determine the effect of H2 relaxin (RLN2) on invasion, migration, and chemosensitivity to cisplatin in human osteosarcoma U2-OS and MG-63 cells and then to investigate the effect of RLN2 on the AKT/NF-κB signaling pathway. The expression of RLN2, p-AKT (Ser473), and p-ERK1/2 (Phospho-Thr202/Tyr204) proteins was detected by western blot in OS tissues from 21 patients with pulmonary metastatic disease, and the correlation between RLN2 and p-AKT or RLN2 and p-ERK1/2 expression was investigated. RLN2 expression was inhibited by RLN2 siRNA transfection in the MG-63 cells. RLN2 was overexpressed in the U2-OS cells by treatment with recombinant relaxin. The results showed that positive relation was found between RLN2 and p-AKT expression in tissues of OS. Silencing RLN2 inhibited cell migratory and invasive ability and angiogenesis formation and increased the chemosensitivity to cisplatin in MG-63 cells. RLN2 overexpression promoted migratory and invasive ability and angiogenesis and increased the chemoresistance to cisplatin in U2-OS cells. Silencing RLN2 inhibited the activity of AKT/NF-κB signaling pathway in MG-63 cells, and vice versa. Blockage of both pathways by specific inhibitors abrogated RLN2-induced survival and invasion of OS cells, and vice versa. Our results indicated RLN2 confers to migratory and invasive ability, angiogenesis, and chemoresistance to cisplatin via modulating the AKT/NF-κB signaling pathway in vitro.
authors.affiliation: Department of Spine, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, Linyi People's Hospital, Linyi, Shandong, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Dialysis Room, Zhangqiu Hospital of Traditional Chinese Medicine, Zhangqiu, Jinan, China.
authors.forename: Zenggang
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Neurology, People's Hospital of Zhangqiu, Jinan, China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Spine, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yue
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics; D012516:Osteosarcoma / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012065:Relaxin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016328:NF-kappa B; C095068:RLN2 protein, human; D034741:RNA, Small Interfering; D012065:Relaxin; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin