Novel lnc-HZ03 and miR-hz03 promote BPDE-induced human trophoblastic cell apoptosis and induce miscarriage by upregulating p53/SAT1 pathway
Normal pregnancy is essential for human reproduction. However, environmental BaP (benzo(a)pyrene) and its metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) induce dysfunctions of human trophoblastic cells, which could further result in miscarriage. Yet, the molecular mechanisms remain po...
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| Veröffentlicht in: | Cell biology and toxicology 2021-12, Vol.37 (6), p.951-970 |
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| creator | Liang, Tingting Xie, Jiayu Zhao, Jingsong Huang, Wenxin Xu, Zhongyan Tian, Peng Mi, Chenyang Dai, Mengyuan Zhang, Shuming Zhang, Huidong |
| description | Normal pregnancy is essential for human reproduction. However, environmental BaP (benzo(a)pyrene) and its metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) induce dysfunctions of human trophoblastic cells, which could further result in miscarriage. Yet, the molecular mechanisms remain poorly understood. In this work, a novel lnc-HZ03 and a novel miR-hz03 were identified. Both lnc-HZ03 and miR-hz03 were highly expressed in human recurrent miscarriage villous tissues and in BPDE-exposed trophoblastic cells. Lnc-HZ03 and miR-hz03 upregulated each other, forming a positive feedback loop. MiR-hz03 could also upregulate p53 level by enhancing its mRNA stability. Both lnc-HZ03 and p53 mRNA contained the target site for miR-hz03 and could directly interact with miR-hz03. It was this target site instead of its mutant on lnc-HZ03 that regulated p53 expression. Subsequently, the upregulated p53 facilitated SAT1 transcription and enhanced SAT1-catalyzed spermine metabolism, which further resulted in trophoblastic cell apoptosis and induced miscarriage. All together, the p53/SAT1 pathway upregulated by lnc-HZ03 and miR-hz03 could promote BPDE-induced human trophoblastic cell apoptosis and the occurrence of miscarriage, shedding novel light on the causes of miscarriage.
Graphical abstract
Lnc-HZ03 and miR-hz03 regulate the occurrence of recurrent miscarriage (RM). In human trophoblastic cells, lnc-HZ03 upregulates miR-hz03 level. MiR-hz03 increases the RNA stability of lnc-HZ03 and p53 mRNA. P53 promotes SAT1 transcription and reduces its cellular spermine content, resulting in cell apoptosis. Under normal conditions, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are downregulated, maintaining normal pregnancy. After exposure to BPDE, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are upregulated and finally induce miscarriage. |
| doi_str_mv | 10.1007/s10565-021-09583-3 |
| format | Article |
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Graphical abstract
Lnc-HZ03 and miR-hz03 regulate the occurrence of recurrent miscarriage (RM). In human trophoblastic cells, lnc-HZ03 upregulates miR-hz03 level. MiR-hz03 increases the RNA stability of lnc-HZ03 and p53 mRNA. P53 promotes SAT1 transcription and reduces its cellular spermine content, resulting in cell apoptosis. Under normal conditions, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are downregulated, maintaining normal pregnancy. After exposure to BPDE, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are upregulated and finally induce miscarriage.</description><identifier>ISSN: 0742-2091</identifier><identifier>EISSN: 1573-6822</identifier><identifier>DOI: 10.1007/s10565-021-09583-3</identifier><identifier>PMID: 33566220</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide ; Abortion, Spontaneous - chemically induced ; Abortion, Spontaneous - genetics ; Apoptosis ; Benzo(a)pyrene ; Benzo(a)pyrene-diol epoxide ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Feedback loops ; Female ; Humans ; Life Sciences ; Metabolites ; MicroRNAs - genetics ; Miscarriage ; Molecular modelling ; mRNA stability ; Original Article ; p53 Protein ; Pharmacology/Toxicology ; Positive feedback ; Pregnancy ; Pyrene ; Spermine ; Transcription ; Tumor Suppressor Protein p53 - genetics</subject><ispartof>Cell biology and toxicology, 2021-12, Vol.37 (6), p.951-970</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-62b694d02ed3ee3ead62eb366d4d19641c29377b93be0fe47a3037bd43d1edfb3</citedby><cites>FETCH-LOGICAL-c375t-62b694d02ed3ee3ead62eb366d4d19641c29377b93be0fe47a3037bd43d1edfb3</cites><orcidid>0000-0001-7845-3331</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10565-021-09583-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10565-021-09583-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33566220$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liang, Tingting</creatorcontrib><creatorcontrib>Xie, Jiayu</creatorcontrib><creatorcontrib>Zhao, Jingsong</creatorcontrib><creatorcontrib>Huang, Wenxin</creatorcontrib><creatorcontrib>Xu, Zhongyan</creatorcontrib><creatorcontrib>Tian, Peng</creatorcontrib><creatorcontrib>Mi, Chenyang</creatorcontrib><creatorcontrib>Dai, Mengyuan</creatorcontrib><creatorcontrib>Zhang, Shuming</creatorcontrib><creatorcontrib>Zhang, Huidong</creatorcontrib><title>Novel lnc-HZ03 and miR-hz03 promote BPDE-induced human trophoblastic cell apoptosis and induce miscarriage by upregulating p53/SAT1 pathway</title><title>Cell biology and toxicology</title><addtitle>Cell Biol Toxicol</addtitle><addtitle>Cell Biol Toxicol</addtitle><description>Normal pregnancy is essential for human reproduction. However, environmental BaP (benzo(a)pyrene) and its metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) induce dysfunctions of human trophoblastic cells, which could further result in miscarriage. Yet, the molecular mechanisms remain poorly understood. In this work, a novel lnc-HZ03 and a novel miR-hz03 were identified. Both lnc-HZ03 and miR-hz03 were highly expressed in human recurrent miscarriage villous tissues and in BPDE-exposed trophoblastic cells. Lnc-HZ03 and miR-hz03 upregulated each other, forming a positive feedback loop. MiR-hz03 could also upregulate p53 level by enhancing its mRNA stability. Both lnc-HZ03 and p53 mRNA contained the target site for miR-hz03 and could directly interact with miR-hz03. It was this target site instead of its mutant on lnc-HZ03 that regulated p53 expression. Subsequently, the upregulated p53 facilitated SAT1 transcription and enhanced SAT1-catalyzed spermine metabolism, which further resulted in trophoblastic cell apoptosis and induced miscarriage. All together, the p53/SAT1 pathway upregulated by lnc-HZ03 and miR-hz03 could promote BPDE-induced human trophoblastic cell apoptosis and the occurrence of miscarriage, shedding novel light on the causes of miscarriage.
Graphical abstract
Lnc-HZ03 and miR-hz03 regulate the occurrence of recurrent miscarriage (RM). In human trophoblastic cells, lnc-HZ03 upregulates miR-hz03 level. MiR-hz03 increases the RNA stability of lnc-HZ03 and p53 mRNA. P53 promotes SAT1 transcription and reduces its cellular spermine content, resulting in cell apoptosis. Under normal conditions, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are downregulated, maintaining normal pregnancy. After exposure to BPDE, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are upregulated and finally induce miscarriage.</description><subject>7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide</subject><subject>Abortion, Spontaneous - chemically induced</subject><subject>Abortion, Spontaneous - genetics</subject><subject>Apoptosis</subject><subject>Benzo(a)pyrene</subject><subject>Benzo(a)pyrene-diol epoxide</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Feedback loops</subject><subject>Female</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Metabolites</subject><subject>MicroRNAs - genetics</subject><subject>Miscarriage</subject><subject>Molecular modelling</subject><subject>mRNA stability</subject><subject>Original Article</subject><subject>p53 Protein</subject><subject>Pharmacology/Toxicology</subject><subject>Positive 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lnc-HZ03 and miR-hz03 promote BPDE-induced human trophoblastic cell apoptosis and induce miscarriage by upregulating p53/SAT1 pathway</title><author>Liang, Tingting ; Xie, Jiayu ; Zhao, Jingsong ; Huang, Wenxin ; Xu, Zhongyan ; Tian, Peng ; Mi, Chenyang ; Dai, Mengyuan ; Zhang, Shuming ; Zhang, Huidong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-62b694d02ed3ee3ead62eb366d4d19641c29377b93be0fe47a3037bd43d1edfb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide</topic><topic>Abortion, Spontaneous - chemically induced</topic><topic>Abortion, Spontaneous - genetics</topic><topic>Apoptosis</topic><topic>Benzo(a)pyrene</topic><topic>Benzo(a)pyrene-diol epoxide</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Feedback loops</topic><topic>Female</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Metabolites</topic><topic>MicroRNAs - genetics</topic><topic>Miscarriage</topic><topic>Molecular modelling</topic><topic>mRNA stability</topic><topic>Original Article</topic><topic>p53 Protein</topic><topic>Pharmacology/Toxicology</topic><topic>Positive feedback</topic><topic>Pregnancy</topic><topic>Pyrene</topic><topic>Spermine</topic><topic>Transcription</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liang, Tingting</creatorcontrib><creatorcontrib>Xie, Jiayu</creatorcontrib><creatorcontrib>Zhao, Jingsong</creatorcontrib><creatorcontrib>Huang, Wenxin</creatorcontrib><creatorcontrib>Xu, Zhongyan</creatorcontrib><creatorcontrib>Tian, Peng</creatorcontrib><creatorcontrib>Mi, Chenyang</creatorcontrib><creatorcontrib>Dai, Mengyuan</creatorcontrib><creatorcontrib>Zhang, 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Collection</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Cell biology and toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liang, Tingting</au><au>Xie, Jiayu</au><au>Zhao, Jingsong</au><au>Huang, Wenxin</au><au>Xu, Zhongyan</au><au>Tian, Peng</au><au>Mi, Chenyang</au><au>Dai, Mengyuan</au><au>Zhang, Shuming</au><au>Zhang, Huidong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel lnc-HZ03 and miR-hz03 promote BPDE-induced human trophoblastic cell apoptosis and induce miscarriage by upregulating p53/SAT1 pathway</atitle><jtitle>Cell biology and toxicology</jtitle><stitle>Cell Biol Toxicol</stitle><addtitle>Cell Biol Toxicol</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>37</volume><issue>6</issue><spage>951</spage><epage>970</epage><pages>951-970</pages><issn>0742-2091</issn><eissn>1573-6822</eissn><abstract>Normal pregnancy is essential for human reproduction. However, environmental BaP (benzo(a)pyrene) and its metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) induce dysfunctions of human trophoblastic cells, which could further result in miscarriage. Yet, the molecular mechanisms remain poorly understood. In this work, a novel lnc-HZ03 and a novel miR-hz03 were identified. Both lnc-HZ03 and miR-hz03 were highly expressed in human recurrent miscarriage villous tissues and in BPDE-exposed trophoblastic cells. Lnc-HZ03 and miR-hz03 upregulated each other, forming a positive feedback loop. MiR-hz03 could also upregulate p53 level by enhancing its mRNA stability. Both lnc-HZ03 and p53 mRNA contained the target site for miR-hz03 and could directly interact with miR-hz03. It was this target site instead of its mutant on lnc-HZ03 that regulated p53 expression. Subsequently, the upregulated p53 facilitated SAT1 transcription and enhanced SAT1-catalyzed spermine metabolism, which further resulted in trophoblastic cell apoptosis and induced miscarriage. All together, the p53/SAT1 pathway upregulated by lnc-HZ03 and miR-hz03 could promote BPDE-induced human trophoblastic cell apoptosis and the occurrence of miscarriage, shedding novel light on the causes of miscarriage.
Graphical abstract
Lnc-HZ03 and miR-hz03 regulate the occurrence of recurrent miscarriage (RM). In human trophoblastic cells, lnc-HZ03 upregulates miR-hz03 level. MiR-hz03 increases the RNA stability of lnc-HZ03 and p53 mRNA. P53 promotes SAT1 transcription and reduces its cellular spermine content, resulting in cell apoptosis. Under normal conditions, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are downregulated, maintaining normal pregnancy. After exposure to BPDE, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are upregulated and finally induce miscarriage.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>33566220</pmid><doi>10.1007/s10565-021-09583-3</doi><tpages>20</tpages><orcidid>https://orcid.org/0000-0001-7845-3331</orcidid></addata></record> |
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| ispartof | Cell biology and toxicology, 2021-12, Vol.37 (6), p.951-970 |
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| subjects | 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide Abortion, Spontaneous - chemically induced Abortion, Spontaneous - genetics Apoptosis Benzo(a)pyrene Benzo(a)pyrene-diol epoxide Biochemistry Biomedical and Life Sciences Cell Biology Feedback loops Female Humans Life Sciences Metabolites MicroRNAs - genetics Miscarriage Molecular modelling mRNA stability Original Article p53 Protein Pharmacology/Toxicology Positive feedback Pregnancy Pyrene Spermine Transcription Tumor Suppressor Protein p53 - genetics |
| title | Novel lnc-HZ03 and miR-hz03 promote BPDE-induced human trophoblastic cell apoptosis and induce miscarriage by upregulating p53/SAT1 pathway |
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