Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling
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Linjie Zhao1,2*, Chuan Yu1,2*, Shengtao Zhou1,2*, Wayne Bond Lau3, Bonnie Lau4, Zhongyue Luo5, Qiao Lin5, Huiliang Yang6, Yu Xuan1,2, Tao Yi1,2, Xia Zhao1,2 and Yuquan Wei1,2
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
* These authors have contributed equally to this work
Shengtao Zhou, email:
keywords: ovarian cancer, PDLIM2, DNA methylation, NOS2, nitric oxide signaling
Received: July 04, 2015 Accepted: November 15, 2015 Published: November 22, 2015
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.
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