title: Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling.
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.
authors.affiliation: 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.|The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Zhao
authors.affiliation: 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.|The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Yu
authors.affiliation: 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.|The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.affiliation: Department of Surgery, Emergency Medicine, Kaiser Permanente Santa Clara Medical Center, Santa Clara, CA, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Lau
authors.affiliation: College of Biological Sciences, Sichuan University, Chengdu, China.
authors.forename: Zhongyue
authors.initials: Z
authors.lastname: Luo
authors.affiliation: College of Biological Sciences, Sichuan University, Chengdu, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Huiliang
authors.initials: H
authors.lastname: Yang
authors.affiliation: 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.|The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xuan
authors.affiliation: 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.|The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.affiliation: 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.|The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: 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.|The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D018572:Disease-Free Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D016513:Mice, SCID; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; C502929:PDLIM2 protein, human; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
keywords: DNA methylation; NOS2; PDLIM2; nitric oxide signaling; ovarian cancer