title: RBEL1 is required for osteosarcoma cell proliferation via inhibiting retinoblastoma 1.
abstract: Osteosarcoma is the most common type of primary malignant tumor of the bone. However, mechanisms underlying osteosarcoma cell proliferation are poorly understood. The present study shows that RBEL1, a newly identified Rab-like GTPase, may be a key regulator of osteosarcoma cell proliferation. Knockdown of RBEL1 in osteosarcoma cells resulted in impaired colony formation and cell proliferation. Cell cycle analysis suggested that RBEL1 depletion induced G1-S arrest in osteosarcoma cells. Furthermore, it was demonstrated that retinoblastoma 1 (Rb) was upregulated and activated following RBEL1 knockdown. In addition, Rb inhibitory downstream targets, such as cyclin A2, cyclin D1, c-Myc and cyclin-dependent kinase 2, were downregulated. Rb knockdown reversed RBEL1 depletion-induced tumor suppressive effects. In conclusion, the present results suggest that RBEL1 modulates cell proliferation and G1‑S transition by inhibiting Rb in osteosarcoma. These results suggest a potential therapeutic target in osteosarcoma.
authors.affiliation: Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Honghui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ji
authors.affiliation: Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yue
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D056751:Cyclin A2 / Q000096:biosynthesis; D019938:Cyclin D1 / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D055785:Gene Knockdown Techniques; D006801:Humans; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000096:biosynthesis* / Q000235:genetics; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C503721:CCNA2 protein, human; C530104:CCND1 protein, human; D056751:Cyclin A2; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D019938:Cyclin D1; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C526916:RABL6 protein, human; D018631:ras Proteins