title: UHRF1 promotes human osteosarcoma cell invasion by downregulating the expression of E‑cadherin in an Rb1‑dependent manner.
abstract: Ubiquitin‑like with plant homeodomain (PHD) and RING‑finger domain 1 (UHRF1) maintains methylation patterns following DNA replication and is expressed at high levels in various types of human cancer. UHRF1 has been identified as a novel oncogene involved in the pathogenesis of hepatocellular carcinoma. Previous studies have demonstrated that inhibition of the expression of UHRF1 suppresses the proliferation of cancer cells. However, the role of UHRF1 in human osteosarcoma has not been investigated. The present study examined the expression levels of UHRF1 and retinoblastoma 1 (Rb1) in human osteosarcoma cell lines by western blot analysis. Stable overexpression of UHRF1 or knockdown of Rb1 was achieved by lentiviral transfection. Subsequently, a Cell Counting Kit-8 assay and a cell invasion assay were performed to detect the biological functions of UHRF1 in vitro. The results of the present study demonstrated that UHRF1 promoted the proliferation of human osteosarcoma cells. The present study also reported that UHRF1 was able to enhance the invasion of osteosarcoma cells in a retinoblastoma 1 (Rb1)‑dependent manner. UHRF1 promoted invasion in Rb1‑positive osteosarcoma cells, but not in Saos‑2 cells with homozygous loss of Rb1. Similarly, knockdown of Rb1 in Rb1‑positive osteosarcoma cells enhanced levels of invasion and eliminated the regulation of invasion by UHRF1. UHRF1 was found to inhibit the mRNA and protein expression levels of Rb1. Furthermore, deletion of Rb1 was found to suppress the expression of E‑cadherin and promote epithelial‑to‑mesenchymal transition (EMT). In addition, the overexpression of UHRF1 inhibited the expression of E‑cadherin and promoted EMT via the suppression of Rb1. These data demonstrated that UHRF1 promotes osteosarcoma cell invasion by downregulating the expression of E‑cadherin and increasing EMT in an Rb1‑dependent manner.
authors.affiliation: Department of Orthopedics, Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 215006, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 215006, P.R. China.
authors.forename: Rui Hong
authors.initials: RH
authors.lastname: Qiao
authors.affiliation: Department of Orthopedics, Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 215006, P.R. China.
authors.forename: Dong Ming
authors.initials: DM
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 226001, P.R. China.
authors.forename: Xiao Wei
authors.initials: XW
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 215006, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 215006, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D015820:Cadherins; D016160:Retinoblastoma Protein; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases