title: Knockdown of CUL4A inhibits invasion and induces apoptosis in osteosarcoma cells.
abstract: Cullin4A (CUL4A) is implicated in many cellular events including cell survival and growth. However, the specific function and underlying mechanisms of CUL4A in cancer invasion have not yet been elucidated. In this work, we were focused on investigating the role of CUL4A in human osteosarcoma (OS). The expression level of CUL4A was evaluated by immunohistochemical (IHC) assay in human OS tissues. Lentivirus-mediated CUL4A shRNA (Lv-shCUL4A) constructed by us was transfected into OS cells for assessing its effects on cell proliferation and invasive potential, respectively detected by MTT and Transwell assays. It was demonstrated that the expression of CUL4A protein was markedly increased in OS tissues compared with the adjacent non-cancerous tissues (ANCT) (57.8% vs. 25.6%, P = 0.019), and was associated with the distant metastases in OS patients (P = 0.016). In vitro, silencing of CUL4A gene inhibited OS cell proliferation and invasion, and induced cell apoptosis, followed by increased expression of p27 and p53 and decreased expression of MMP-2. Therefore, these findings indicate that elevated expression of CUL4A is positively correlated with distant metastases in OS patients, and knockdown of CUL4A suppresses invasion and induces apoptosis in OS cells, suggesting that CUL4A may serve as a potential target for the treatment of OS.
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China shaojiang201502@163.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Shao
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D044842:Cullin Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C114234:CUL4A protein, human; D044842:Cullin Proteins; D034741:RNA, Small Interfering
keywords: CUL4A; invasion; osteosarcoma; proliferation