UHRF1 promotes human osteosarcoma cell invasion by downregulating the expression of E‑cadherin in an Rb1‑dependent manner

Liu,Wei; Qiao,Rui Hong; Wang,Dong Ming; Huang,Xiao  Wei; Li,Bing; Wang,Dong

doi:10.3892/mmr.2015.4515

UHRF1 promotes human osteosarcoma cell invasion by downregulating the expression of E‑cadherin in an Rb1‑dependent manner

Authors:
- Wei Liu
- Rui Hong Qiao
- Dong Ming Wang
- Xiao Wei Huang
- Bing Li
- Dong Wang
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Affiliations: Department of Orthopedics, Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 215006, P.R. China, Department of Gastroenterology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 226001, P.R. China
Published online on: November 6, 2015 https://doi.org/10.3892/mmr.2015.4515
Pages: 315-320

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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.

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