title: Alteration of Pituitary Tumor Transforming Gene-1 Regulates Trophoblast Invasion via the Integrin/Rho-Family Signaling Pathway.
abstract: Trophoblast invasion ability is an important factor in early implantation and placental development. Recently, pituitary tumor transforming gene 1 (PTTG1) was shown to be involved in invasion and proliferation of cancer. However, the role of PTTG1 in trophoblast invasion remains unknown. Thus, in this study we analyzed PTTG1 expression in trophoblasts and its effect on trophoblast invasion activity and determined the mechanism through which PTTG1 regulates trophoblast invasion. Trophoblast proliferation and invasion abilities, regardless of PTTG1 expression, were analyzed by quantitative real-time polymerase chain reaction, fluorescence-activated cell sorting analysis, invasion assay, western blot, and zymography after treatment with small interfering RNA against PTTG1 (siPTTG1). Additionally, integrin/Rho-family signaling in trophoblasts by PTTG1 alteration was analyzed. Furthermore, the effect of PTTG1 on trophoblast invasion was evaluated by microRNA (miRNA) mimic and inhibitor treatment. Trophoblast invasion was significantly reduced through decreased matrix metalloproteinase (MMP)-2 and MMP-9 expression when PTTG1 expression was inhibited by siPTTG1 (p < 0.05). Furthermore, knockdown of PTTG1 increased expression of integrin alpha 4 (ITGA4), ITGA5, and integrin beta 1 (ITGB1); otherwise, RhoA expression was significantly decreased (p < 0.05). Treatment of miRNA-186-5p mimic and inhibitor controlled trophoblast invasion ability by altering PTTG1 and MMP expression. PTTG1 can control trophoblast invasion ability via regulation of MMP expression through integrin/Rho-family signaling. In addition, PTTG1 expression and its function were regulated by miRNA-186-5p. These results help in understanding the mechanism through which PTTG1 regulates trophoblast invasion and thereby implantation and placental development.
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam-si, 463-400, Republic of Korea.
authors.forename: Seung Mook
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam-si, 463-400, Republic of Korea.
authors.forename: Hee Yeon
authors.initials: HY
authors.lastname: Jang
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, CHA University, Seoul, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, CHA University, Seoul, Republic of Korea.
authors.forename: Joong Sik
authors.initials: JS
authors.lastname: Shin
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Yoon
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam-si, 463-400, Republic of Korea.
authors.forename: Gi Jin
authors.initials: GJ
authors.lastname: Kim
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D064249:Securin / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016023:Integrins; C552431:MIRN185 microRNA, human; D035683:MicroRNAs; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; C066737:RHOA protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D020742:rhoA GTP-Binding Protein