Exogenous expression of UHRF1 promotes proliferation and metastasis of breast cancer cells

Abstract

Abstract. In the present study, we investigated the role of UHRF1 (ubiquitin-like protein containing PHD and RING finger domains 1) in proliferation, invasion and migration of breast cancer cells, and the potential mechanisms were also explored. Cell proliferation was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; cell cycle distribution and apoptosis were evaluated using flow cytometry; protein expression was determined by western blotting; angiogenesis of xenografts was assessed by microvessel density (MVD); cell invasion was measured using transwell chamber; cell migration was determined by wound scratching assay. Our results demonstrated that UHRF1 transfection conferred serum independence to MDA-MB-231 cells, G 1 phase shortage and apoptosis suppression, accompanied with an increased expression of cyclin D 1 and decreased expression of Bax. Significant pro-invasion and pro-migration activity was observed, with no obvious effect on the expression of PTEN and maspin. Co-expression of the UHRF1/PTEN or UHRF1/maspin degraded the role of UHRF1 in regulating invasion and migration. UHRF1 induced growth of MDA-MB-231 cells by promoting tumor vessel formation in vivo. In conclusion, UHRF1 promoted the proliferation of breast cancer cells by apoptosis inhibition, G 1 phase shortage and promotion of tumor vessel formation, and pro-invasion and pro-migration activity was also observed by interacting with PTEN and maspin. Thus, UHRF1 may serve as a new therapy target for breast cancer.

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

“…Furthermore, the overexpression of UHRF1 destabilizes and delocalizes DNMT1, and causes DNA hypomethylation in cancer cells (19). Although several studies have demonstrated the function of UHRF1 in tumorigenesis and tumor progression (14,17,20), little is known regarding the function of UHRF1 in human osteosarcoma cells. In the present study, the expression of UHRF1 was detected in all of the human osteosarcoma cell lines examined.…”

“…Through interaction with other nuclear proteins, including Tip60, histone deacetylase and G9A, UHRF1 may function as a bridge between DNA methylation and the histone methylation (12). Furthermore, significant overexpression of UHRF1 has been observed in several types of human tumor, including breast (13,14), bladder (15), prostate (16) and lung cancer (17). The overexpression of UHRF1 has also been reported to reduce the radiosensitivity of human breast cancer cells and HeLa cells to γ-irradiation (18).…”

Structural Insight into Coordinated Recognition of Trimethylated Histone H3 Lysine 9 (H3K9me3) by the Plant Homeodomain (PHD) and Tandem Tudor Domain (TTD) of UHRF1 (Ubiquitin-like, Containing PHD and RING Finger Domains, 1) Protein

“…Up-regulations of UHRF1 were observed in various cancer cells, including breast, prostate, and lung cancer (24,34,35). In cancer cells, UHRF1 plays a key role in promoting proliferation, and its abundance remains at high levels in all phases of the cell cycle (24,31,36,37). Thus, UHRF1 is a potential drug target for cancer therapy and a biomarker for diagnosis (38).…”

Quantitative Proteomic Analysis of the Metastasis-Inhibitory Mechanism of miR-193a-3p in Non-Small Cell Lung Cancer

“…It was found that UHRF1 could promote the G1/S transition as a direct target of E2F1, which is a transcriptional factor essential for S-phase entry [30]. In examining many human cancers, including lung cancer, breast cancer and colorectal cancer [31,32,33], we have found that UHRF1 could promote their proliferation and metastasis.…”