Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1: Implications for preeclampsia development
Preeclampsia (PE) is a major contributor to maternal morbidity and mortality. However, the molecular mechanisms underlying PE progression are not well characterized. Here, we investigated the role of miR-218 in PE development. The expression of miR-218 and its host genes SLIT2 and SLIT3 was up-regul...
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| Veröffentlicht in: | The international journal of biochemistry & cell biology 2017-06, Vol.87, p.95-103 |
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| creator | Fang, Min Du, Hechun Han, Bing Xia, Guiyu Shi, Xiaoliang Zhang, Feng Fu, Qiqin Zhang, Tao |
| description | Preeclampsia (PE) is a major contributor to maternal morbidity and mortality. However, the molecular mechanisms underlying PE progression are not well characterized. Here, we investigated the role of miR-218 in PE development. The expression of miR-218 and its host genes SLIT2 and SLIT3 was up-regulated in preeclamptic placentae compared to normal placentae. miR-218 expression was induced by hypoxia and decreased after knockdown of HIF-1α in an extravillous trophoblast cell line (HTR-8/SVneo). Chromatin immunoprecipitation assays showed direct binding of HIF-1α to the promoters of SLIT2 and SLIT3. Bioinformatics analysis identified LASP1 as a direct target of miR-218. Overexpression of miR-218 repressed the expression of LASP1 at both the mRNA and protein level. Meanwhile, miR-218 repressed the activity of a luciferase reporter containing the 3′-untranslated region of the LASP1 gene. Furthermore, expression of LASP1 rescued the inhibitory effect of miR-218 on HTR-8/SVneo cell invasion. Together, these results indicated that miR-218 contributes to PE by targeting LASP1 to inhibit trophoblast invasion. |
| doi_str_mv | 10.1016/j.biocel.2017.04.005 |
| format | Article |
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However, the molecular mechanisms underlying PE progression are not well characterized. Here, we investigated the role of miR-218 in PE development. The expression of miR-218 and its host genes SLIT2 and SLIT3 was up-regulated in preeclamptic placentae compared to normal placentae. miR-218 expression was induced by hypoxia and decreased after knockdown of HIF-1α in an extravillous trophoblast cell line (HTR-8/SVneo). Chromatin immunoprecipitation assays showed direct binding of HIF-1α to the promoters of SLIT2 and SLIT3. Bioinformatics analysis identified LASP1 as a direct target of miR-218. Overexpression of miR-218 repressed the expression of LASP1 at both the mRNA and protein level. Meanwhile, miR-218 repressed the activity of a luciferase reporter containing the 3′-untranslated region of the LASP1 gene. Furthermore, expression of LASP1 rescued the inhibitory effect of miR-218 on HTR-8/SVneo cell invasion. Together, these results indicated that miR-218 contributes to PE by targeting LASP1 to inhibit trophoblast invasion.</description><identifier>ISSN: 1357-2725</identifier><identifier>EISSN: 1878-5875</identifier><identifier>DOI: 10.1016/j.biocel.2017.04.005</identifier><identifier>PMID: 28412444</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Cell Line ; Cytoskeletal Proteins - genetics ; Female ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Intercellular Signaling Peptides and Proteins - genetics ; LASP1 ; LIM Domain Proteins - genetics ; Membrane Proteins - genetics ; MicroRNAs - genetics ; miR-218 ; Nerve Tissue Proteins - genetics ; Pre-Eclampsia - genetics ; Pre-Eclampsia - pathology ; Preeclampsia ; Pregnancy ; Trophoblast invasion ; Trophoblasts - pathology ; Up-Regulation - genetics</subject><ispartof>The international journal of biochemistry & cell biology, 2017-06, Vol.87, p.95-103</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-306969197ca19b3acfc7354df94e688c11fd66e33b642d947a6c48ddadac93823</citedby><cites>FETCH-LOGICAL-c362t-306969197ca19b3acfc7354df94e688c11fd66e33b642d947a6c48ddadac93823</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1357272517300833$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28412444$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fang, Min</creatorcontrib><creatorcontrib>Du, Hechun</creatorcontrib><creatorcontrib>Han, Bing</creatorcontrib><creatorcontrib>Xia, Guiyu</creatorcontrib><creatorcontrib>Shi, Xiaoliang</creatorcontrib><creatorcontrib>Zhang, Feng</creatorcontrib><creatorcontrib>Fu, Qiqin</creatorcontrib><creatorcontrib>Zhang, Tao</creatorcontrib><title>Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1: Implications for preeclampsia development</title><title>The international journal of biochemistry & cell biology</title><addtitle>Int J Biochem Cell Biol</addtitle><description>Preeclampsia (PE) is a major contributor to maternal morbidity and mortality. However, the molecular mechanisms underlying PE progression are not well characterized. Here, we investigated the role of miR-218 in PE development. The expression of miR-218 and its host genes SLIT2 and SLIT3 was up-regulated in preeclamptic placentae compared to normal placentae. miR-218 expression was induced by hypoxia and decreased after knockdown of HIF-1α in an extravillous trophoblast cell line (HTR-8/SVneo). Chromatin immunoprecipitation assays showed direct binding of HIF-1α to the promoters of SLIT2 and SLIT3. Bioinformatics analysis identified LASP1 as a direct target of miR-218. Overexpression of miR-218 repressed the expression of LASP1 at both the mRNA and protein level. Meanwhile, miR-218 repressed the activity of a luciferase reporter containing the 3′-untranslated region of the LASP1 gene. Furthermore, expression of LASP1 rescued the inhibitory effect of miR-218 on HTR-8/SVneo cell invasion. Together, these results indicated that miR-218 contributes to PE by targeting LASP1 to inhibit trophoblast invasion.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Cell Line</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>LASP1</subject><subject>LIM Domain Proteins - genetics</subject><subject>Membrane Proteins - genetics</subject><subject>MicroRNAs - genetics</subject><subject>miR-218</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Pre-Eclampsia - genetics</subject><subject>Pre-Eclampsia - pathology</subject><subject>Preeclampsia</subject><subject>Pregnancy</subject><subject>Trophoblast invasion</subject><subject>Trophoblasts - pathology</subject><subject>Up-Regulation - genetics</subject><issn>1357-2725</issn><issn>1878-5875</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMuO1DAQRS0EYh7wBwh5ySYZv2I7LJBaI2BGagHisbYcuzLjVhIH292i-Xo86oElqypV3VtXdRB6RUlLCZVXu3YI0cHUMkJVS0RLSPcEnVOtdNNp1T2tPe9UwxTrztBFzjtCCO0Yf47OmBaUCSHO0e-b4xp_BduExe9dGCbAc3Apfv20aRjVOCz3YQgl45Lieh-HyeZShwebQ1zwcMTFpjsoYbnD2823L_Qtvp3XKThb6j7jMSa8JgA32XnNwWIPB5jiOsNSXqBno50yvHysl-jHh_ffr2-a7eePt9ebbeO4ZKXhRPayp71ylvYDt250infCj70AqbWjdPRSAueDFMz3QlnphPbeeut6rhm_RG9Od9cUf-4hFzOHXMFNdoG4z4ZqrftOScWrVJyklUDOCUazpjDbdDSUmAfqZmdO1M0DdUOEqdSr7fVjwn6Ywf8z_cVcBe9OAqh_HgIkk12AxYEPCVwxPob_J_wBERuWtw</recordid><startdate>201706</startdate><enddate>201706</enddate><creator>Fang, Min</creator><creator>Du, Hechun</creator><creator>Han, Bing</creator><creator>Xia, Guiyu</creator><creator>Shi, Xiaoliang</creator><creator>Zhang, Feng</creator><creator>Fu, Qiqin</creator><creator>Zhang, Tao</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>201706</creationdate><title>Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1: Implications for preeclampsia development</title><author>Fang, Min ; Du, Hechun ; Han, Bing ; Xia, Guiyu ; Shi, Xiaoliang ; Zhang, Feng ; Fu, Qiqin ; Zhang, Tao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-306969197ca19b3acfc7354df94e688c11fd66e33b642d947a6c48ddadac93823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Cell Line</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>LASP1</topic><topic>LIM Domain Proteins - genetics</topic><topic>Membrane Proteins - genetics</topic><topic>MicroRNAs - genetics</topic><topic>miR-218</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Pre-Eclampsia - genetics</topic><topic>Pre-Eclampsia - pathology</topic><topic>Preeclampsia</topic><topic>Pregnancy</topic><topic>Trophoblast invasion</topic><topic>Trophoblasts - pathology</topic><topic>Up-Regulation - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fang, Min</creatorcontrib><creatorcontrib>Du, Hechun</creatorcontrib><creatorcontrib>Han, Bing</creatorcontrib><creatorcontrib>Xia, Guiyu</creatorcontrib><creatorcontrib>Shi, Xiaoliang</creatorcontrib><creatorcontrib>Zhang, Feng</creatorcontrib><creatorcontrib>Fu, Qiqin</creatorcontrib><creatorcontrib>Zhang, Tao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The international journal of biochemistry & cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fang, Min</au><au>Du, Hechun</au><au>Han, Bing</au><au>Xia, Guiyu</au><au>Shi, Xiaoliang</au><au>Zhang, Feng</au><au>Fu, Qiqin</au><au>Zhang, Tao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1: Implications for preeclampsia development</atitle><jtitle>The international journal of biochemistry & cell biology</jtitle><addtitle>Int J Biochem Cell Biol</addtitle><date>2017-06</date><risdate>2017</risdate><volume>87</volume><spage>95</spage><epage>103</epage><pages>95-103</pages><issn>1357-2725</issn><eissn>1878-5875</eissn><abstract>Preeclampsia (PE) is a major contributor to maternal morbidity and mortality. However, the molecular mechanisms underlying PE progression are not well characterized. Here, we investigated the role of miR-218 in PE development. The expression of miR-218 and its host genes SLIT2 and SLIT3 was up-regulated in preeclamptic placentae compared to normal placentae. miR-218 expression was induced by hypoxia and decreased after knockdown of HIF-1α in an extravillous trophoblast cell line (HTR-8/SVneo). Chromatin immunoprecipitation assays showed direct binding of HIF-1α to the promoters of SLIT2 and SLIT3. Bioinformatics analysis identified LASP1 as a direct target of miR-218. Overexpression of miR-218 repressed the expression of LASP1 at both the mRNA and protein level. Meanwhile, miR-218 repressed the activity of a luciferase reporter containing the 3′-untranslated region of the LASP1 gene. Furthermore, expression of LASP1 rescued the inhibitory effect of miR-218 on HTR-8/SVneo cell invasion. Together, these results indicated that miR-218 contributes to PE by targeting LASP1 to inhibit trophoblast invasion.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>28412444</pmid><doi>10.1016/j.biocel.2017.04.005</doi><tpages>9</tpages></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - genetics Cell Line Cytoskeletal Proteins - genetics Female Humans Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - genetics Intercellular Signaling Peptides and Proteins - genetics LASP1 LIM Domain Proteins - genetics Membrane Proteins - genetics MicroRNAs - genetics miR-218 Nerve Tissue Proteins - genetics Pre-Eclampsia - genetics Pre-Eclampsia - pathology Preeclampsia Pregnancy Trophoblast invasion Trophoblasts - pathology Up-Regulation - genetics |
| title | Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1: Implications for preeclampsia development |
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