STAT3 acetylation-induced promoter methylation is associated with downregulation of the ARHI tumor-suppressor gene in ovarian cancer

Li,Jie; Cui,Geng; Sun,Lu; Wang,Shu-Juan; Li,Ya-Li; Meng,Yuan-Guang; Guan,Zheng; Fan,Wen-Sheng; Li,Li-An; Yang,Yi-Zhuo; You,Yan-Qin; Fu,Xiao-Yu; Yan,Zhi-Feng; Huang,Ke

doi:10.3892/or.2013.2414

July 2013 Volume 30 Issue 1

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July 2013 Volume 30 Issue 1

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Article

STAT3 acetylation-induced promoter methylation is associated with downregulation of the ARHI tumor-suppressor gene in ovarian cancer

Authors:
- Jie Li
- Geng Cui
- Lu Sun
- Shu-Juan Wang
- Ya-Li Li
- Yuan-Guang Meng
- Zheng Guan
- Wen-Sheng Fan
- Li-An Li
- Yi-Zhuo Yang
- Yan-Qin You
- Xiao-Yu Fu
- Zhi-Feng Yan
- Ke Huang
View Affiliations / Copyright

Affiliations: Department of Gynecology and Obstetrics, General Hospital of PLA, Beijing 100853, P.R. China, Department of Orthopedics, General Hospital of PLA, Beijing 100853, P.R. China, Department of Pathology, General Hospital of PLA, Beijing 100853, P.R. China
Pages: 165-170
|
Published online on: April 22, 2013

https://doi.org/10.3892/or.2013.2414
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Abstract

ARHI is a Ras-related imprinted tumor-suppressor gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of ovarian cancer cells, and promoter methylation is considered to be associated with its loss of expression. however, the underlying mechanisms are not well understood. Thus, the present study aimed to investigate the specific functions of ARHI and its methylation in ovarian cancer cell proliferation. Furthermore, we examined the possible role of acetylated STAT3 in modulating the expression of ARHI and its methylation. In accordance with the majority of previous studies, reduced ARHI expression was found in epithelial ovarian cancer tissues and cancer cell lines as indicated by immunohistochemistry and RT-PCR. In addition, CpG islands Ⅰ and Ⅱ within ARHI promoter regions were partially methylated or hypermethylated in cancer cell lines (SKOV-3 and HO-8910) as analyzed by pyrosequencing assays, resulting in enhanced proliferation of the cancer cells. This proliferation was reversed by the administration of 5-aza-2'-deoxycytidine. Subsequently, we demonstrated that STAT3 acetylation was increased in HO-8910 cells, and the methylation status of CpG Ⅰ was altered in response to the acetylation of STAT3 using western blotting. Finally, chromatin immunoprecipitation (ChIP) and IP analysis indicated that acetylated STAT3 bound to the ARHI promoter and recruited DNA methyltransferase 1 for genetic modification. In conclusion, acetylated STAT3-induced promoter gene methylation accounts for the loss of ARHI expression and cancer cell proliferation.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

STAT3 acetylation-induced promoter methylation is associated with downregulation of the ARHI tumor-suppressor gene in ovarian cancer

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