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

Authors

• Linjie Zhao, Department of Gynecology and Obstetrics, Key Lab. of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Edu., West China Second Hospital, Chengdu, China; The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaFollow
• Chuan Yu, Department of Gynecology and Obstetrics, Key Lab. of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Edu., West China Second Hospital, Chengdu, China; The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
• Shengtao Zhou, Department of Gynecology and Obstetrics, Key Lab. of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Edu., West China Second Hospital, Chengdu, China; The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaFollow
• Wayne Bond Lau, Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, United StatesFollow
• Bonnie Lau, Department of Surgery, Emergency Medicine, Kaiser Permanente Santa Clara Medical Center, Santa Clara, CA, United StatesFollow
• Zhongyue Luo, College of Biological Sciences, Sichuan University, Chengdu, ChinaFollow
• Qiao Lin, College of Biological Sciences, Sichuan University, Chengdu, China
• Huiliang Yang, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, ChinaFollow
• Yu Xuan, Department of Gynecology and Obstetrics, Key Lab. of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Edu., West China Second Hospital, Chengdu, China; The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaFollow
• Tao Yi, Department of Gynecology and Obstetrics, Key Lab. of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Edu., West China Second Hospital, Chengdu, China; The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaFollow
• Xia Zhao, Department of Gynecology and Obstetrics, Key Lab. of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Edu., West China Second Hospital, Chengdu, China; The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaFollow
• Yuquan Wei, Department of Gynecology and Obstetrics, Key Lab. of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Edu., West China Second Hospital, Chengdu, China; The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaFollow

Document Type

Article

Publication Date

1-12-2016

Comments

This article has been peer reviewed. It was published in: Oncotarget.

Volume 7, Issue 2, 2016, Pages 1408-1420.

The published version is available at DOI: 10.18632/oncotarget.6368

Copyright © 2016 The Authors

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.

Recommended Citation

Zhao, Linjie; Yu, Chuan; Zhou, Shengtao; Lau, Wayne Bond; Lau, Bonnie; Luo, Zhongyue; Lin, Qiao; Yang, Huiliang; Xuan, Yu; Yi, Tao; Zhao, Xia; and Wei, Yuquan, "Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling." (2016). Department of Emergency Medicine Faculty Papers. Paper 42.
https://jdc.jefferson.edu/emfp/42

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

PubMed ID

26593252