J Cancer 2017; 8(19):4027-4039. doi:10.7150/jca.21256

Research Paper

UHRF1 is an Independent Prognostic Factor and a Potential Therapeutic Target of Esophageal Squamous Cell Carcinoma

Jiecheng Ye1, 2*, Yong Zhang3*, Weiye Liang1, 2, Jianxian Huang1, 2, Lihui Wang1, 2✉, Xueyun Zhong1, 2✉

1. Department of Pathology, Medical College, Jinan University, Guangzhou 510632, China;
2. Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Jinan University, Guangzhou 510632, China;
3. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
*Contributed to this work equally

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Ye J, Zhang Y, Liang W, Huang J, Wang L, Zhong X. UHRF1 is an Independent Prognostic Factor and a Potential Therapeutic Target of Esophageal Squamous Cell Carcinoma. J Cancer 2017; 8(19):4027-4039. doi:10.7150/jca.21256. Available from http://www.jcancer.org/v08p4027.htm

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Purpose: Ubiquitin-like with plant homeodomain and ring-finger domains 1 (UHRF1) plays an essential role in DNA methylation, and the overexpression of UHRF1 is associated with poor prognosis in various cancers. Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90% of esophageal cancer cases in China, but the five-year survival rate for patients is less than 10% due to limited clinical approaches for early diagnosis and treatment. The present research aimed to investigate the expression of UHRF1 in ESCC and its biological role in ESCC development.

Methods: UHRF1 expression in ESCC and normal esophageal tissues was examined using immunohistochemical staining, followed by analysis of the correlation between UHRF1 expression and clinical features. In addition, the effects of lentivirus-mediated RNA interference of UHRF1 on global DNA methylation, cell proliferation, cell cycle progression and apoptosis and were investigated in ESCC cells.

Results: UHRF1 was overexpressed in ESCC tissues and was an independent prognostic factor for ESCC patients. In ESCC cells, knockdown of UHRF1 caused global DNA hypomethylation, inhibited cell proliferation and induced apoptosis. Furthermore, UHRF1 depletion induced cell cycle arrest at the G2/M phase, accompanied by activation of Wee1 and DNA damage response pathway.

Conclusions: Our findings identify UHRF1 as a promising prognostic marker for ESCC and suggest that UHRF1 may be a potential therapy target for ESCC patients with elevated UHRF1 expression.

Keywords: DNA methylation, esophageal squamous cell carcinoma, prognosis, UHRF1, Wee1