Pathologic significance of SET/I2PP2A-mediated PP2A and non-PP2A pathways in polycystic ovary syndrome (PCOS).
SET (SE translocation, SET), a constitutive inhibitor of protein phosphatase 2A (PP2A), is a multifunctional oncoprotein involved in DNA replication, histone modification, nucleosome assembly, gene transcription and cell proliferation. It is widely expressed in human tissues including the gonadal system and brain. Intensive studies have shown that overexpressed SET plays an important role in the development of Alzheimer's disease (AD), and may also contribute to the malignant transformation of breast and ovarian cancers. Recent studies indicated that through interaction with PP2A, SET may upregulate androgen biosynthesis and contribute to hyperandrogenism in polycystic ovary syndrome (PCOS) patients. This review article summarizes data concerning the SET expression in ovaries from PCOS and normal women, and analyzes the role/regulatory mechanism of SET for androgen biosynthesis in PCOS, as well as the significance of this action in the development of PCOS. The potential value of SET-triggered pathway as a therapeutic target and the application of anti-SET reagents for treating hyperandrogenism in PCOS patients are also discussed.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, USA. Electronic address: jiang_s@mercer.edu.
Shi-Wen
SW
Jiang
Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, USA; The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Siliang
S
Xu
Department of Histology and Embryology, Shantou University Medical College, Shantou, Guangdong 515000, China.
Haibin
H
Chen
The Third People's Hospital of Qingdao, Department of Obstetrics and Gynecology, Qingdao, Shandong 266041, China; Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Xiaoqiang
X
Liu
Department of Medical Genetics, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Zuoqing
Z
Tang
The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Yugui
Y
Cui
The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China. Electronic address: jyliu_nj@126.com.
Jiayin
J
Liu
D021581:Active Transport, Cell Nucleus; D000818:Animals; D004268:DNA-Binding Proteins; D005260:Female; D056488:Histone Chaperones / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009865:Oocytes / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C513473:SET protein, human; D014157:Transcription Factors; D054648:Protein Phosphatase 2
Androgen; Anti-SET; Hyperandrogenism; PCOS; PP2A; SET