title: Hyaluronic acid promotes the expression of progesterone receptor membrane component 1 via epigenetic silencing of miR-139-5p in human and rat granulosa cells.
abstract: Primary ovarian insufficiency (POI) is a serious reproductive dysfunction in which the follicle pool is reduced and depleted. Abnormal apoptosis of ovarian granulosa cells (GCs) is believed to result in follicle loss. Progesterone receptor membrane component 1 (PGRMC1), which is critical for GC survival, was reported to be reduced in POI patients, but the mechanism is unknown. In the present study, we found that PGRMC1 expression was correlated with the level of hyaluronic acid (HA) in POI patients. HA up-regulated PGRMC1 expression in GCs via suppression of miR-139-5p, which was proven by Western blotting and luciferase reporter assays to target PGRMC1. Consistent with these findings, levels of miR-139-5p were significantly increased and presented an inverse correlation with PGRMC1 in POI patients. Noticeably, HA inhibited CD44-mediated miR-139-5p expression but had no effect on luciferase activity after insertion of miR-139 promoter into luciferase plasmid. Interestingly, miR-139-5p was significantly up-regulated in KGN cells (GC tumor cell line) by the histone deacetylase inhibitor trichostatin A, indicating that HA down-regulated miR-139-5p expression via histone deacetylation. Taken together, we report an unrecognized mechanism of HA in the promotion of PGRMC1 expression, suggesting that HA may be a potential molecule for the prevention and treatment of POI.
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Immunology and Reproductive Biology Laboratory, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Immunology and Reproductive Biology Laboratory, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Fang
authors.affiliation: Immunology and Reproductive Biology Laboratory, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China yayihou@nju.edu.cn.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China yali_hu@hotmail.com.
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016649:Primary Ovarian Insufficiency / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C555098:MIRN139 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C115296:PGRMC1 protein, human; C486424:Pgrmc1 protein, rat; D011980:Receptors, Progesterone; D006820:Hyaluronic Acid
keywords: hyaluronic acid; miR-139-5p; primary ovarian insufficiency; progesterone receptor membrane component 1