title: DRP5 is involved in cancer cell growth and predicts poor prognosis in human osteosarcoma.
abstract: Osteosarcoma is an extremely aggressive primary malignant bone tumor of childhood. Collapsin response mediator proteins (CRMPs), which are highly expressed in the developing nervous system, were recently shown to be associated with cancer development. However, the relationship between DRP5 (CRMP5) and osteosarcoma has not been evaluated. In this study, we investigated the role of DRP5 in the regulation of osteosarcoma growth. DRP5 mRNA and protein levels were significantly upregulated in human osteosarcoma cell lines and associated with increased migration and invasion. Genetic knockdown of DRP5 markedly suppressed the expression of matrix metalloproteinase (MMP)-2 and MMP-9. DRP5 silencing significantly inhibited osteosarcoma cell growth in vitro and in a xenograft mouse model in vivo. Microarray immunohistochemical analysis of osteosarcoma specimens and Kaplan-Meier analysis showed that patients with high DRP5 protein expression had shorter overall survival than those with low DRP5 levels. Taken together, these results suggest that DRP5 plays a critical role in the regulation of osteosarcoma and could be a potential therapeutic target and prognostic factor in osteosarcoma.
authors.affiliation: Department of Oncology, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Weihai
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Hengtao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xianbiao
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Changye
authors.initials: C
authors.lastname: Zou
authors.affiliation: Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Junqiang
authors.identifier: http://orcid.org/0000-0003-0176-3512
authors.initials: J
authors.lastname: Yin
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006867:Hydrolases; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C415087:DPYSL5 protein, human; D006867:Hydrolases; D020782:Matrix Metalloproteinases
keywords: Animal model; DRP5; invasion; lung metastasis; migration; osteosarcoma; overall survival