Overexpression of UHRF1 and its potential role in the development of invasive ductal breast cancer validated by integrative bioinformatics and immunohistochemistry analyses

Abstract

Background Increasing evidence has highlighted the role of ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1) in the development of cancers, including hepatocellular carcinoma, pancreatic cancer, and bladder cancer. However, the correlation between UHRF1 and breast cancer remains unclear. The present study aimed to analyze the expression of UHRF1 and its role in the development of invasive ductal breast cancer (IDC) by integrating multilevel expression data and immunohistochemistry analysis. Methods The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to gather UHRF1 expression data on IDC. Additionally, immunohistochemistry analysis was used to investigate the correlations between UHRF1 expression and the clinical characteristics of IDC. Results The GEO and TCGA databases indicated that UHRF1 was up-regulated in IDC. Consistently, the immunohistochemical specimens showed that the significant overexpression of UHRF1 in IDC, and its expression level showed an increasing trend from ductal carcinomas in situ to IDC. Notably, the increased levels of UHRF1 were closely correlated with estrogen receptor expression, pathological grade, and the prognosis of the disease. In addition, patients with a high UHRF1 expression had a poorer prognosis. Conclusions In conclusion, our findings suggested that UHRF1 plays a promoting role in breast tumorigenesis, and the over-expression of UHRF1 could serve as a biomarker for the prognosis in invasive ductal carcinomas in breast cancer.

Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia

“…UHRF1 expression in epithelial tumors positively correlates with the stage, grade, drug resistance, and maintenance of cancer stem cell characteristics and has been suggested as a putative oncogene [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Moreover, high tumoral expression of UHRF1 is associated with poor prognosis of several cancer types, including hepatocellular carcinoma, pancreatic, breast, and bladder cancer [ 10 , 11 , 12 , 13 ].…”

Molecular basis of hUHRF1 allosteric activation for synergistic histone modification binding by PI5P

“…UHRF1 acts as a safeguard of the genome by maintaining global DNA methylation levels, protecting chromatin from DNA damaging agents, maintaining higher-order chromatin structures, and silencing repetitive DNA elements (15)(16)(17)(18)(19)(20). UHRF1 is up-regulated in various types of malignancies, including breast, liver, and pancreatic cancer, where it plays a crucial role in promoting proliferation (21)(22)(23).…”

Molecular basis of UHRF1 allosteric activation for synergistic histone modification binding by PI5P

“…UHRF1 acts as a safeguard of the genome by maintaining global DNA methylation levels, protecting chromatin from DNA damaging agents, maintaining higher-order chromatin structures and silencing repetitive DNA elements [4][5][6][7][8][9][10] . Accordingly, the protein is upregulated in various types of malignancies [11][12][13][14] .UHRF1 is composed of five domains that are connected through flexible linkers (Fig. 1a).…”