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Oncotarget. 2016 Jan 12;7(2):1408-20. doi: 10.18632/oncotarget.6368.

Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling.

Zhao L1,2, Yu C1,2, Zhou S1,2, Lau WB3, Lau B4, Luo Z5, Lin Q5, Yang H6, Xuan Y1,2, Yi T1,2, Zhao X1,2, Wei Y1,2.

Author information

1
Department of Gynecology and Obstetrics, Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Chengdu, China.
2
The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
3
Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
4
Department of Surgery, Emergency Medicine, Kaiser Permanente Santa Clara Medical Center, Santa Clara, CA, USA.
5
College of Biological Sciences, Sichuan University, Chengdu, China.
6
Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Ovarian cancer constitutes one of the most lethal gynaecological malignancies worldwide and currently no satisfactory therapeutic approaches have been established. Therefore, elucidation of molecular mechanisms to develop targeted therapy of ovarian cancer is crucial. PDLIM2 is critical to promote ubiquitination of nuclear p65 and thus its role in inflammation has been highlighted recently. We demonstrate that PDLIM2 is decreased in both ovarian high-grade serous carcinoma and in various human ovarian cancer cell lines compared with normal ovary tissues and human ovarian surface epithelial cells (HOSE). Further functional analysis revealed that PDLIM2 is epigenetically repressed in ovarian cancer development and inhibition of PDLIM2 promoted ovarian cancer growth both in vivo and in vitro via NOS2-derived nitric oxide signaling, leading to recruitment of M2 type macrophages. These results suggest that PDLIM2 might be involved in ovarian cancer pathogenesis, which could serve as a promising therapeutic target for ovarian cancer patients.

KEYWORDS:

DNA methylation; NOS2; PDLIM2; nitric oxide signaling; ovarian cancer

PMID:
26593252
PMCID:
PMC4811469
DOI:
10.18632/oncotarget.6368
[Indexed for MEDLINE]
Free PMC Article

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