WTAP dysregulation‐mediated HMGN3‐m6A modification inhibited trophoblast invasion in early‐onset preeclampsia
Early‐onset preeclampsia (ePE) originates from abnormal implantation and placentation that involves trophoblast invasion, but its pathophysiology is not entirely understood. N6‐methyladenosine (m6A) regulators mediate the progression of various cancers. The invasiveness of trophoblast cells is simil...
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| creator | Bian, Yue Li, Jiapo Shen, Hongfei Li, Yuanyuan Hou, Yue Huang, Ling Song, Guiyu Qiao, Chong |
| description | Early‐onset preeclampsia (ePE) originates from abnormal implantation and placentation that involves trophoblast invasion, but its pathophysiology is not entirely understood. N6‐methyladenosine (m6A) regulators mediate the progression of various cancers. The invasiveness of trophoblast cells is similar to that of tumor cells. However, little is known regarding the potential role of m6A modification in ePE and the underlying mechanism. This study aimed to explore the m6A level in placental tissue samples collected from ePE patients and to investigate whether m6A modification was an essential part of PE pathogenesis. The m6A level in placental tissue samples of 80 PE participants was examined. MeRIP‐microarray, RNA‐Seq, luciferase reporter assay, and RNA immunoprecipitation chip (RIP) assay were performed. The m6A level in the ePE group was significantly reduced compared with the control group. Wilms' tumor 1‐associating protein (WTAP) regulated trophoblast cell migration and invasion. Mechanistically, the high mobility group nucleosomal binding domain 3 (HMGN3) gene was a target gene of WTAP in trophoblast (p |
| doi_str_mv | 10.1096/fj.202200700RR |
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N6‐methyladenosine (m6A) regulators mediate the progression of various cancers. The invasiveness of trophoblast cells is similar to that of tumor cells. However, little is known regarding the potential role of m6A modification in ePE and the underlying mechanism. This study aimed to explore the m6A level in placental tissue samples collected from ePE patients and to investigate whether m6A modification was an essential part of PE pathogenesis. The m6A level in placental tissue samples of 80 PE participants was examined. MeRIP‐microarray, RNA‐Seq, luciferase reporter assay, and RNA immunoprecipitation chip (RIP) assay were performed. The m6A level in the ePE group was significantly reduced compared with the control group. Wilms' tumor 1‐associating protein (WTAP) regulated trophoblast cell migration and invasion. Mechanistically, the high mobility group nucleosomal binding domain 3 (HMGN3) gene was a target gene of WTAP in trophoblast (p < .05). WTAP enhanced the stability of HMGN3 mRNA through binding with its 3’‐UTR m6A site(+485A, +522A). HMGN3 was recognized by m6A recognition protein insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1), which was inhibited when knocking down WTAP. Both m6A and WTAP levels were downregulated in ePE. The m6A modification mediated by WTAP/IGF2BP1/HMGN3 axis might contribute to abnormal trophoblast invasion. Our work provided a foundation for further exploration of RNA epigenetic regulatory patterns in ePE, and indicated a new treatment strategy for ePE.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.202200700RR</identifier><identifier>PMID: 36412513</identifier><language>eng</language><publisher>United States</publisher><subject>Cell Cycle Proteins - metabolism ; early‐onset preeclampsia ; Female ; Humans ; N6‐methyladenosine ; Placenta - metabolism ; Pre-Eclampsia - genetics ; preeclampsia ; Pregnancy ; RNA - metabolism ; RNA Splicing Factors ; RNA, Messenger - genetics ; trophoblast ; Trophoblasts - metabolism ; WTAP</subject><ispartof>The FASEB journal, 2022-12, Vol.36 (12), p.e22617-n/a</ispartof><rights>2022 The Authors. published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.</rights><rights>2022 The Authors. 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N6‐methyladenosine (m6A) regulators mediate the progression of various cancers. The invasiveness of trophoblast cells is similar to that of tumor cells. However, little is known regarding the potential role of m6A modification in ePE and the underlying mechanism. This study aimed to explore the m6A level in placental tissue samples collected from ePE patients and to investigate whether m6A modification was an essential part of PE pathogenesis. The m6A level in placental tissue samples of 80 PE participants was examined. MeRIP‐microarray, RNA‐Seq, luciferase reporter assay, and RNA immunoprecipitation chip (RIP) assay were performed. The m6A level in the ePE group was significantly reduced compared with the control group. Wilms' tumor 1‐associating protein (WTAP) regulated trophoblast cell migration and invasion. Mechanistically, the high mobility group nucleosomal binding domain 3 (HMGN3) gene was a target gene of WTAP in trophoblast (p < .05). WTAP enhanced the stability of HMGN3 mRNA through binding with its 3’‐UTR m6A site(+485A, +522A). HMGN3 was recognized by m6A recognition protein insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1), which was inhibited when knocking down WTAP. Both m6A and WTAP levels were downregulated in ePE. The m6A modification mediated by WTAP/IGF2BP1/HMGN3 axis might contribute to abnormal trophoblast invasion. Our work provided a foundation for further exploration of RNA epigenetic regulatory patterns in ePE, and indicated a new treatment strategy for ePE.</description><subject>Cell Cycle Proteins - metabolism</subject><subject>early‐onset preeclampsia</subject><subject>Female</subject><subject>Humans</subject><subject>N6‐methyladenosine</subject><subject>Placenta - metabolism</subject><subject>Pre-Eclampsia - genetics</subject><subject>preeclampsia</subject><subject>Pregnancy</subject><subject>RNA - metabolism</subject><subject>RNA Splicing Factors</subject><subject>RNA, Messenger - genetics</subject><subject>trophoblast</subject><subject>Trophoblasts - metabolism</subject><subject>WTAP</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkL1OwzAURi0EoqWwMqKMLCnXduLEY6loi1R-VIoYI9uxqaukCXEKysYj8Iw8CSktiI3pSvee79PVQegUQx8DZxdm2SdACEAEMJvtoS4OKfgsZrCPuhBz4jNG4w46cm4JABgwO0QdygJMQky7yD3NB_de2rhKP68zUdti9fn-kevUilqn3uRmfEs3Czbw8iK1xqpvxrOrhZV2g9RVUS4KmQlXt9tX4bZnT4sqa9posXK69spKa5WJvHRWHKMDIzKnT3azhx5HV_PhxJ_eja-Hg6mvaIwjPww2_8tYBMRIGegUEzAgGZUKlGzrKJecKyw5CVRqQixTKamOMRHagBG0h863vWVVvKy1q5PcOqWzTKx0sXYJiSgHFnEOLdrfoqoqXOvCJGVlc1E1CYZkIzoxy-SP6DZwtutey9bWL_5jtgXCLfBmM938U5eMHi4JIQxH9AvClI6b</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Bian, Yue</creator><creator>Li, Jiapo</creator><creator>Shen, Hongfei</creator><creator>Li, Yuanyuan</creator><creator>Hou, Yue</creator><creator>Huang, Ling</creator><creator>Song, Guiyu</creator><creator>Qiao, Chong</creator><scope>24P</scope><scope>WIN</scope><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><orcidid>https://orcid.org/0000-0002-4979-3545</orcidid></search><sort><creationdate>202212</creationdate><title>WTAP dysregulation‐mediated HMGN3‐m6A modification inhibited trophoblast invasion in early‐onset preeclampsia</title><author>Bian, Yue ; Li, Jiapo ; Shen, Hongfei ; Li, Yuanyuan ; Hou, Yue ; Huang, Ling ; Song, Guiyu ; Qiao, Chong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3817-540892b8a42fbb4ed120f0b63bc0cbeec39b99c1b924cdf51bdbb3e812aef0fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Cell Cycle Proteins - metabolism</topic><topic>early‐onset preeclampsia</topic><topic>Female</topic><topic>Humans</topic><topic>N6‐methyladenosine</topic><topic>Placenta - metabolism</topic><topic>Pre-Eclampsia - genetics</topic><topic>preeclampsia</topic><topic>Pregnancy</topic><topic>RNA - metabolism</topic><topic>RNA Splicing Factors</topic><topic>RNA, Messenger - genetics</topic><topic>trophoblast</topic><topic>Trophoblasts - metabolism</topic><topic>WTAP</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bian, Yue</creatorcontrib><creatorcontrib>Li, Jiapo</creatorcontrib><creatorcontrib>Shen, Hongfei</creatorcontrib><creatorcontrib>Li, Yuanyuan</creatorcontrib><creatorcontrib>Hou, Yue</creatorcontrib><creatorcontrib>Huang, Ling</creatorcontrib><creatorcontrib>Song, Guiyu</creatorcontrib><creatorcontrib>Qiao, Chong</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><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 FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bian, Yue</au><au>Li, Jiapo</au><au>Shen, Hongfei</au><au>Li, Yuanyuan</au><au>Hou, Yue</au><au>Huang, Ling</au><au>Song, Guiyu</au><au>Qiao, Chong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>WTAP dysregulation‐mediated HMGN3‐m6A modification inhibited trophoblast invasion in early‐onset preeclampsia</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2022-12</date><risdate>2022</risdate><volume>36</volume><issue>12</issue><spage>e22617</spage><epage>n/a</epage><pages>e22617-n/a</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Early‐onset preeclampsia (ePE) originates from abnormal implantation and placentation that involves trophoblast invasion, but its pathophysiology is not entirely understood. N6‐methyladenosine (m6A) regulators mediate the progression of various cancers. The invasiveness of trophoblast cells is similar to that of tumor cells. However, little is known regarding the potential role of m6A modification in ePE and the underlying mechanism. This study aimed to explore the m6A level in placental tissue samples collected from ePE patients and to investigate whether m6A modification was an essential part of PE pathogenesis. The m6A level in placental tissue samples of 80 PE participants was examined. MeRIP‐microarray, RNA‐Seq, luciferase reporter assay, and RNA immunoprecipitation chip (RIP) assay were performed. The m6A level in the ePE group was significantly reduced compared with the control group. Wilms' tumor 1‐associating protein (WTAP) regulated trophoblast cell migration and invasion. Mechanistically, the high mobility group nucleosomal binding domain 3 (HMGN3) gene was a target gene of WTAP in trophoblast (p < .05). WTAP enhanced the stability of HMGN3 mRNA through binding with its 3’‐UTR m6A site(+485A, +522A). HMGN3 was recognized by m6A recognition protein insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1), which was inhibited when knocking down WTAP. Both m6A and WTAP levels were downregulated in ePE. The m6A modification mediated by WTAP/IGF2BP1/HMGN3 axis might contribute to abnormal trophoblast invasion. Our work provided a foundation for further exploration of RNA epigenetic regulatory patterns in ePE, and indicated a new treatment strategy for ePE.</abstract><cop>United States</cop><pmid>36412513</pmid><doi>10.1096/fj.202200700RR</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0002-4979-3545</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cell Cycle Proteins - metabolism early‐onset preeclampsia Female Humans N6‐methyladenosine Placenta - metabolism Pre-Eclampsia - genetics preeclampsia Pregnancy RNA - metabolism RNA Splicing Factors RNA, Messenger - genetics trophoblast Trophoblasts - metabolism WTAP |
| title | WTAP dysregulation‐mediated HMGN3‐m6A modification inhibited trophoblast invasion in early‐onset preeclampsia |
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