Alteration of Pituitary Tumor Transforming Gene-1 Regulates TrophoblastInvasion via the Integrin/Rho-Family Signaling Pathway
| Autor: | Joong Sik Shin, Hee Yeon Jang, Gi Jin Kim, Sun Hwa Park, Ji Eun Lee, Seung Mook Lim, Bo Hyun Yoon |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Embryology Integrins Small interfering RNA RHOA Placenta Maternal Health lcsh:Medicine Biochemistry 0302 clinical medicine Pregnancy Gene expression Medicine and Health Sciences Small interfering RNAs Cell Cycle and Cell Division lcsh:Science reproductive and urinary physiology Regulation of gene expression Gene knockdown Multidisciplinary biology Obstetrics and Gynecology Trophoblasts Extracellular Matrix Cell biology Nucleic acids Securin medicine.anatomical_structure Matrix Metalloproteinase 9 Cell Processes 030220 oncology & carcinogenesis embryonic structures Matrix Metalloproteinase 2 Cellular Structures and Organelles Anatomy Signal transduction Research Article Cell Line 03 medical and health sciences microRNA Cell Adhesion Genetics medicine Humans Non-coding RNA Cell Proliferation lcsh:R Reproductive System Biology and Life Sciences Trophoblast Cell Biology Molecular biology Gene regulation MicroRNAs 030104 developmental biology Gene Expression Regulation biology.protein RNA Women's Health lcsh:Q Blastocysts rhoA GTP-Binding Protein Developmental Biology |
| Zdroj: | PLOS ONE(11): 2 PLoS ONE PLoS ONE, Vol 11, Iss 2, p e0149371 (2016) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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