HDAC1/DNMT3A-Containing Complex Is Associated with Suppression of Oct4 in Cervical Cancer Cells

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Dongbo Liu^1,2#, Peng Zhou^1#, Li Zhang¹, Wei Gong¹, Gang Huang¹, Yingru Zheng^3*, and Fengtian He^1*

¹Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China; fax: +86-23-68752262; E-mail: hefengtian06@yahoo.com.cn; liu.db1980@yahoo.com.cn

²Depeartment 1 of State Key Laboratory of Trauma, Burns, and Combined Injury, Daping Hospital and Institute of Surgery Research, 10 Changjiang Road, Daping, Chongqing 400042, China

³Department of Obstetrics and Gynecology, Daping Hospital and Institute of Surgery Research, 10 Changjiang Road, Daping, Chongqing 400042, China; E-mail: zhengyingru65@tom.com

^# Contributed equally to this work.

^* To whom correspondence should be addressed.

Received December 15, 2011; Revision received March 28, 2012

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Octamer-binding transcription factor 4 (Oct4), an important embryonic transcriptional factor, is highly expressed in several tumors and is considered as a hallmark of cancer stem cells. Knowledge about the expression and regulatory mechanisms of Oct4 can contribute to the treatment of cancers. As for cervical cancer, however, details remain obscure about Oct4 expression and its regulatory mechanism. In this study, we found that the level of Oct4 in human papillomavirus 16 (HPV16)- positive cervical cancer cells (CaSki cells) was higher than that in HPV-negative cervical cancer cells (C-33A cells), whereas both the level of histone deacetylase 1 (HDAC1) and DNA methyltransferase 3A (DNMT3A) were lower in CaSki cells than those in C-33A cells. Treatment with valproic acid, an HDAC inhibitor, could significantly increase the expression of Oct4 in C-33A cells, but only slightly increased Oct4 in CaSki cells. Co-immunoprecipitation assays showed that HDAC1 and DNMT3A existed in a common complex. The co-immunoprecipitated DNMT3A or HDAC1 was dose-dependently decreased with valproic acid treatment. These results indicated that HDAC1/DNMT3A-containing complex is associated with the suppression of Oct4 in cervical cancer cells, and the activity of HDAC1 is required in the repression of Oct4.

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KEY WORDS: Oct4, cervical cancer, HDAC1, DNMT3A, HPV16

DOI: 10.1134/S0006297912080159

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