Alteration of Pituitary Tumor Transforming Gene-1 Regulates Trophoblast Invasion via the Integrin/Rho-Family Signaling Pathway
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 th...
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| creator | Lim, Seung Mook Jang, Hee Yeon Lee, Ji Eun Shin, Joong Sik Park, Sun-Hwa Yoon, Bo Hyun Kim, Gi Jin |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0149371 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0149371</identifier><identifier>PMID: 26900962</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Achievement tests ; Antigens ; Biology and Life Sciences ; Brain cancer ; Cancer ; Cell adhesion & migration ; Cell cycle ; Cell Line ; Cell Proliferation ; Flow cytometry ; Fluorescence ; Gelatinase B ; Gene expression ; Gene Expression Regulation ; Gynecology ; Humans ; Hypoxia ; Implantation ; Inhibitors ; Integrins - biosynthesis ; Integrins - genetics ; Kinases ; Lung cancer ; Matrix metalloproteinase ; Matrix Metalloproteinase 2 - biosynthesis ; Matrix Metalloproteinase 2 - genetics ; Matrix Metalloproteinase 9 - biosynthesis ; Matrix Metalloproteinase 9 - genetics ; Medical research ; Medicine ; Medicine and Health Sciences ; Metalloproteinase ; MicroRNAs ; MicroRNAs - biosynthesis ; MicroRNAs - genetics ; miRNA ; Obstetrics ; Penicillin ; Pituitary ; Pituitary gland ; Pituitary tumor-transforming proteins ; Placenta ; Polymerase chain reaction ; Pregnancy ; rhoA GTP-Binding Protein - biosynthesis ; rhoA GTP-Binding Protein - genetics ; RhoA protein ; Ribonucleic acid ; RNA ; Science ; Securin - genetics ; Securin - metabolism ; Senescence ; Signal transduction ; siRNA ; Trophoblasts ; Trophoblasts - cytology ; Trophoblasts - metabolism ; Tumors</subject><ispartof>PloS one, 2016-02, Vol.11 (2), p.e0149371-e0149371</ispartof><rights>2016 Lim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>Achievement tests</subject><subject>Antigens</subject><subject>Biology and Life Sciences</subject><subject>Brain cancer</subject><subject>Cancer</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell Line</subject><subject>Cell Proliferation</subject><subject>Flow cytometry</subject><subject>Fluorescence</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Implantation</subject><subject>Inhibitors</subject><subject>Integrins - biosynthesis</subject><subject>Integrins - genetics</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 2 - 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metabolism</subject><subject>Senescence</subject><subject>Signal transduction</subject><subject>siRNA</subject><subject>Trophoblasts</subject><subject>Trophoblasts - cytology</subject><subject>Trophoblasts - metabolism</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1r2zAUNWNj7br9g7EZ-rIXp_qw5OhlUMraBQorXfYsrq1rR8G2MknOyMt--5QlLe0YCCTOPffo3MvJsveUzCiv6MXaTX6EfrZxI84ILVUCX2SnVHFWSEb4yyfvk-xNCGtCBJ9L-To7YVIRoiQ7zX5f9hE9ROvG3LX5nY2TjeB3-XIanM-XHsbQOj_YsctvcMSC5vfYTT1EDKnqNitX9xBivhi3EPYqWwt5XGECInbejhf3K1dcw2D7Xf7ddsnyXusO4uoX7N5mr1roA7473mfZj-svy6uvxe23m8XV5W3RCCZjgZwKVtPSzGtDgLXCkMaUEkqGoJoaVYNUloxJygUXRMG8bOYCOadIjKGMn2UfD7qb3gV9XF3QVAkiFCdVlRiLA8M4WOuNt0PagnZg9V_A-U6Dj7bpUTPkphVpm4BQGmhqxVAZUYJkCWUmaX0-_jbVA5oGx-ihfyb6vDLale7cVpeVTIckgU9HAe9-ThiiHmxosO9hRDcl35WsFJVivp_s_B_q_6crD6zGuxA8to9mKNH7OD106X2c9DFOqe3D00Eemx7yw_8AqRDKxw</recordid><startdate>20160222</startdate><enddate>20160222</enddate><creator>Lim, Seung Mook</creator><creator>Jang, Hee Yeon</creator><creator>Lee, Ji Eun</creator><creator>Shin, Joong Sik</creator><creator>Park, Sun-Hwa</creator><creator>Yoon, Bo Hyun</creator><creator>Kim, Gi Jin</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160222</creationdate><title>Alteration of Pituitary Tumor Transforming Gene-1 Regulates Trophoblast Invasion via the Integrin/Rho-Family Signaling Pathway</title><author>Lim, Seung Mook ; Jang, Hee Yeon ; Lee, Ji Eun ; Shin, Joong Sik ; Park, Sun-Hwa ; Yoon, Bo Hyun ; Kim, Gi Jin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-e3152b14d8bd0a2f5d0cd46a42ea9cbe9ce1642261353509a84c85e331e0dd123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Achievement tests</topic><topic>Antigens</topic><topic>Biology and Life Sciences</topic><topic>Brain cancer</topic><topic>Cancer</topic><topic>Cell adhesion & migration</topic><topic>Cell cycle</topic><topic>Cell Line</topic><topic>Cell Proliferation</topic><topic>Flow cytometry</topic><topic>Fluorescence</topic><topic>Gelatinase B</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Gynecology</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Implantation</topic><topic>Inhibitors</topic><topic>Integrins - biosynthesis</topic><topic>Integrins - genetics</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 2 - biosynthesis</topic><topic>Matrix Metalloproteinase 2 - genetics</topic><topic>Matrix Metalloproteinase 9 - biosynthesis</topic><topic>Matrix Metalloproteinase 9 - genetics</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metalloproteinase</topic><topic>MicroRNAs</topic><topic>MicroRNAs - biosynthesis</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>Obstetrics</topic><topic>Penicillin</topic><topic>Pituitary</topic><topic>Pituitary gland</topic><topic>Pituitary tumor-transforming proteins</topic><topic>Placenta</topic><topic>Polymerase chain reaction</topic><topic>Pregnancy</topic><topic>rhoA GTP-Binding Protein - biosynthesis</topic><topic>rhoA GTP-Binding Protein - genetics</topic><topic>RhoA protein</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Science</topic><topic>Securin - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26900962</pmid><doi>10.1371/journal.pone.0149371</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1950593077 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Achievement tests Antigens Biology and Life Sciences Brain cancer Cancer Cell adhesion & migration Cell cycle Cell Line Cell Proliferation Flow cytometry Fluorescence Gelatinase B Gene expression Gene Expression Regulation Gynecology Humans Hypoxia Implantation Inhibitors Integrins - biosynthesis Integrins - genetics Kinases Lung cancer Matrix metalloproteinase Matrix Metalloproteinase 2 - biosynthesis Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 9 - biosynthesis Matrix Metalloproteinase 9 - genetics Medical research Medicine Medicine and Health Sciences Metalloproteinase MicroRNAs MicroRNAs - biosynthesis MicroRNAs - genetics miRNA Obstetrics Penicillin Pituitary Pituitary gland Pituitary tumor-transforming proteins Placenta Polymerase chain reaction Pregnancy rhoA GTP-Binding Protein - biosynthesis rhoA GTP-Binding Protein - genetics RhoA protein Ribonucleic acid RNA Science Securin - genetics Securin - metabolism Senescence Signal transduction siRNA Trophoblasts Trophoblasts - cytology Trophoblasts - metabolism Tumors |
| title | Alteration of Pituitary Tumor Transforming Gene-1 Regulates Trophoblast Invasion via the Integrin/Rho-Family Signaling Pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T19%3A06%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Alteration%20of%20Pituitary%20Tumor%20Transforming%20Gene-1%20Regulates%20Trophoblast%20Invasion%20via%20the%20Integrin/Rho-Family%20Signaling%20Pathway&rft.jtitle=PloS%20one&rft.au=Lim,%20Seung%20Mook&rft.date=2016-02-22&rft.volume=11&rft.issue=2&rft.spage=e0149371&rft.epage=e0149371&rft.pages=e0149371-e0149371&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0149371&rft_dat=%3Cproquest_plos_%3E1767916582%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1950593077&rft_id=info:pmid/26900962&rft_doaj_id=oai_doaj_org_article_2e3df5005aea4dacb92e9d54a625002d&rfr_iscdi=true |