UHRF1 silences gelsolin to inhibit cell death in early stage cervical cancer
- Lee, Han Ju; Kim, Min Jun; Kim, Yoon Sook; Choi, Mee Young; Cho, Gyeong Jae; Choi, Wan Sung
- Issue Date
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Cervical cancer; DNA methylation; Gelsolin; HPV; UHRF1
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.526, no.4, pp.1061 - 1068
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Start Page
- End Page
- Persistent infection with high-risk strains of human papillomavirus (HPV) is the primary cause of cervical cancer, the fourth most common cancer among women worldwide. Two oncoproteins encoded by the HPV genome, E6 and E7, are required for epigenetic modifications that promote cervical cancer development. We found that knockdown of HPV E6/E7 by siRNA reduced the levels of ubiquitin-like containing PHD and RING finger domain 1 (UHRF1) but increased the levels of gelsolin (GSN) in early stage cervical cancer cells. In addition, we found that UHRF1 levels were increased and GSN levels were decreased in early stage cervical cancer compared with those in normal cervical tissues, as shown by Western blot analysis, immunohistochemistry, and analysis of the Oncomine database. Moreover, knockdown of UHRF1 resulted in increased cell death in cervical cancer cell lines. Treatment of E6/E7-transformed HaCaT (HEK001) cells and HeLa cells with the DNA-hypomethylating agent 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor Trichostatin A increased GSN expression levels. UHRF1 knockdown in HEK001 cells by siRNA or the UHRF1 antagonist thymoquinone increased GSN levels, induced cell cycle arrest and apoptosis, and increased the levels of p27 and cleaved PARP. Those results indicate that upregulation of UHRF1 by HPV E6/E7 causes GSN silencing and a reduction of cell death in early stage cervical cancer, suggesting that GSN might be a useful therapeutic target in early stage cervical cancer. (C) 2020 Elsevier Inc. All rights reserved.
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- College of Medicine > Department of Medicine > Journal Articles
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