Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene FCGRT by MicroRNA-3181

Purpose FCGRT encodes the alpha-chain component of the neonatal Fc receptor (FcRn). FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn...

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Veröffentlicht in:Pharmaceutical research 2018-01, Vol.35 (1), p.15-9, Article 15
Hauptverfasser: Ferguson, Daniel C., Blanco, Javier G.
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description Purpose FCGRT encodes the alpha-chain component of the neonatal Fc receptor (FcRn). FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn by two microRNAs ( hsa-miR-3181 and hsa-miR-3136-3p ) acting on FCGRT . Methods The binding of candidate microRNAs to the 3′-untranslated region of FCGRT was evaluated using luciferase reporter constructs in CHO cells. The effect of microRNAs on FCGRT mRNA and FcRn protein expression was evaluated using specific microRNA mimics and inhibitor transfections in A549, HEK293 and HepG2 cells. Results Hsa-miR-3181 mimic reduced luciferase reporter activity by 70.1% (10 nM, P  
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FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn by two microRNAs ( hsa-miR-3181 and hsa-miR-3136-3p ) acting on FCGRT . Methods The binding of candidate microRNAs to the 3′-untranslated region of FCGRT was evaluated using luciferase reporter constructs in CHO cells. The effect of microRNAs on FCGRT mRNA and FcRn protein expression was evaluated using specific microRNA mimics and inhibitor transfections in A549, HEK293 and HepG2 cells. Results Hsa-miR-3181 mimic reduced luciferase reporter activity by 70.1% (10 nM, P  &lt; 0.0001). In A549, HEK293 and HepG2 cells, hsa-miR-3181 decreased FCGRT mRNA expression (48.6%, 51.3% and 43.5% respectively, 25 nM, P  &lt; 0.05). The hsa-miR-3181 mimic decreased the expression of FcRn protein by 40% after 48 h (25 nM, P  &lt; 0.001). The mature form of hsa-miR-3181 was detected in samples of human liver. Conclusions These data suggest that hsa-miR-3181 is an epigenetic regulator of FCGRT expression. The identification of this regulator of FCGRT may provide insights into a potential determinant of interindividual variability in FcRn expression.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-017-2294-0</identifier><identifier>PMID: 29302759</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>3' Untranslated Regions ; A549 Cells ; Albumin ; Animals ; Biochemistry ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; CHO Cells ; Cricetinae ; Cricetulus ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Fc receptors ; Gene Expression ; HEK293 Cells ; Hep G2 Cells ; Histocompatibility Antigens Class I - biosynthesis ; Histocompatibility Antigens Class I - genetics ; Humans ; Immunoglobulin G ; Infants (Newborn) ; Liver ; Liver - metabolism ; Luciferases ; Medical Law ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Monoclonal antibodies ; Neonates ; Newborn babies ; Pharmacology/Toxicology ; Pharmacy ; Receptors, Fc - biosynthesis ; Receptors, Fc - genetics ; Research Paper ; RNA, Messenger - genetics ; Tissues ; Transfection - methods</subject><ispartof>Pharmaceutical research, 2018-01, Vol.35 (1), p.15-9, Article 15</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018</rights><rights>COPYRIGHT 2018 Springer</rights><rights>Pharmaceutical Research is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-f30a060c372b80e45210c5c88a6f547c7fd7aaa75f55cfd0ff0644c4283496383</citedby><cites>FETCH-LOGICAL-c537t-f30a060c372b80e45210c5c88a6f547c7fd7aaa75f55cfd0ff0644c4283496383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11095-017-2294-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-017-2294-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29302759$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ferguson, Daniel C.</creatorcontrib><creatorcontrib>Blanco, Javier G.</creatorcontrib><title>Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene FCGRT by MicroRNA-3181</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Purpose FCGRT encodes the alpha-chain component of the neonatal Fc receptor (FcRn). FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn by two microRNAs ( hsa-miR-3181 and hsa-miR-3136-3p ) acting on FCGRT . Methods The binding of candidate microRNAs to the 3′-untranslated region of FCGRT was evaluated using luciferase reporter constructs in CHO cells. The effect of microRNAs on FCGRT mRNA and FcRn protein expression was evaluated using specific microRNA mimics and inhibitor transfections in A549, HEK293 and HepG2 cells. Results Hsa-miR-3181 mimic reduced luciferase reporter activity by 70.1% (10 nM, P  &lt; 0.0001). In A549, HEK293 and HepG2 cells, hsa-miR-3181 decreased FCGRT mRNA expression (48.6%, 51.3% and 43.5% respectively, 25 nM, P  &lt; 0.05). The hsa-miR-3181 mimic decreased the expression of FcRn protein by 40% after 48 h (25 nM, P  &lt; 0.001). The mature form of hsa-miR-3181 was detected in samples of human liver. Conclusions These data suggest that hsa-miR-3181 is an epigenetic regulator of FCGRT expression. The identification of this regulator of FCGRT may provide insights into a potential determinant of interindividual variability in FcRn expression.</description><subject>3' Untranslated Regions</subject><subject>A549 Cells</subject><subject>Albumin</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Fc receptors</subject><subject>Gene Expression</subject><subject>HEK293 Cells</subject><subject>Hep G2 Cells</subject><subject>Histocompatibility Antigens Class I - biosynthesis</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>Humans</subject><subject>Immunoglobulin G</subject><subject>Infants (Newborn)</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Luciferases</subject><subject>Medical Law</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Monoclonal antibodies</subject><subject>Neonates</subject><subject>Newborn babies</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Receptors, Fc - biosynthesis</subject><subject>Receptors, Fc - genetics</subject><subject>Research Paper</subject><subject>RNA, Messenger - genetics</subject><subject>Tissues</subject><subject>Transfection - methods</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1klGLEzEUhYMobl39Ab5IwBdfst5MksnkRSjFdoV1hVLBt5CmSZtlJqmTGWH_vRm6ll1R8hBIvntu7slB6C2FKwogP2ZKQQkCVJKqUpzAMzSjQjKigP94jmYgK04ayekFepXzHQA0VPGX6KJSDCop1Axt1m4_tmYIKeLk8XBw-HrsTMRLS25dimYwLV47645D6rFpjwdDFgcTIl656PBysVpv8PYefw22T-vbOWG0oa_RC2_a7N487Jfo-_LzZnFNbr6tvizmN8QKJgfiGRiowTJZbRtwXFQUrLBNY2ovuLTS76QxRgovhPU78B5qzi2vGsZVzRp2iT6ddI_jtnM76-LQm1Yf-9CZ_l4nE_TTmxgOep9-aSFFsQaKwIcHgT79HF0edBeydW1roktj1lQ1qjxVclHQ93-hd2nsYxlvongtlSqunqm9aZ0O0afS106iel46VpTWbKKu_kGVtXNdsCk6H8r5kwJ6Kigm59w7f56Rgp6ioE9R0CUKeoqCnmZ799icc8Wfvy9AdQJyuYp71z-a6L-qvwFRd7p-</recordid><startdate>20180101</startdate><enddate>20180101</enddate><creator>Ferguson, Daniel C.</creator><creator>Blanco, Javier G.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</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>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180101</creationdate><title>Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene FCGRT by MicroRNA-3181</title><author>Ferguson, Daniel C. ; Blanco, Javier G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-f30a060c372b80e45210c5c88a6f547c7fd7aaa75f55cfd0ff0644c4283496383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>3' Untranslated Regions</topic><topic>A549 Cells</topic><topic>Albumin</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Fc receptors</topic><topic>Gene Expression</topic><topic>HEK293 Cells</topic><topic>Hep G2 Cells</topic><topic>Histocompatibility Antigens Class I - biosynthesis</topic><topic>Histocompatibility Antigens Class I - genetics</topic><topic>Humans</topic><topic>Immunoglobulin G</topic><topic>Infants (Newborn)</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Luciferases</topic><topic>Medical Law</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>Monoclonal antibodies</topic><topic>Neonates</topic><topic>Newborn babies</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Receptors, Fc - biosynthesis</topic><topic>Receptors, Fc - genetics</topic><topic>Research Paper</topic><topic>RNA, Messenger - genetics</topic><topic>Tissues</topic><topic>Transfection - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferguson, Daniel C.</creatorcontrib><creatorcontrib>Blanco, Javier G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Proquest Nursing &amp; 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Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferguson, Daniel C.</au><au>Blanco, Javier G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene FCGRT by MicroRNA-3181</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2018-01-01</date><risdate>2018</risdate><volume>35</volume><issue>1</issue><spage>15</spage><epage>9</epage><pages>15-9</pages><artnum>15</artnum><issn>0724-8741</issn><eissn>1573-904X</eissn><abstract>Purpose FCGRT encodes the alpha-chain component of the neonatal Fc receptor (FcRn). FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn by two microRNAs ( hsa-miR-3181 and hsa-miR-3136-3p ) acting on FCGRT . Methods The binding of candidate microRNAs to the 3′-untranslated region of FCGRT was evaluated using luciferase reporter constructs in CHO cells. The effect of microRNAs on FCGRT mRNA and FcRn protein expression was evaluated using specific microRNA mimics and inhibitor transfections in A549, HEK293 and HepG2 cells. Results Hsa-miR-3181 mimic reduced luciferase reporter activity by 70.1% (10 nM, P  &lt; 0.0001). In A549, HEK293 and HepG2 cells, hsa-miR-3181 decreased FCGRT mRNA expression (48.6%, 51.3% and 43.5% respectively, 25 nM, P  &lt; 0.05). The hsa-miR-3181 mimic decreased the expression of FcRn protein by 40% after 48 h (25 nM, P  &lt; 0.001). The mature form of hsa-miR-3181 was detected in samples of human liver. Conclusions These data suggest that hsa-miR-3181 is an epigenetic regulator of FCGRT expression. The identification of this regulator of FCGRT may provide insights into a potential determinant of interindividual variability in FcRn expression.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>29302759</pmid><doi>10.1007/s11095-017-2294-0</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects 3' Untranslated Regions
A549 Cells
Albumin
Animals
Biochemistry
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
CHO Cells
Cricetinae
Cricetulus
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Fc receptors
Gene Expression
HEK293 Cells
Hep G2 Cells
Histocompatibility Antigens Class I - biosynthesis
Histocompatibility Antigens Class I - genetics
Humans
Immunoglobulin G
Infants (Newborn)
Liver
Liver - metabolism
Luciferases
Medical Law
MicroRNA
MicroRNAs
MicroRNAs - genetics
miRNA
Monoclonal antibodies
Neonates
Newborn babies
Pharmacology/Toxicology
Pharmacy
Receptors, Fc - biosynthesis
Receptors, Fc - genetics
Research Paper
RNA, Messenger - genetics
Tissues
Transfection - methods
title Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene FCGRT by MicroRNA-3181
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