Zhao Jingsong, Cheng Liqin, Liu Qicai, Liang Tingting, Xie Jiayu, Wang Rong, Chen Weina, Ao Lin, Zhang Huidong
Research Center for Environment and Female Reproductive Health, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China.
Department of Obstetrics and Gynecology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China.
Toxicol Sci. 2023 Feb 17;191(2):332-342. doi: 10.1093/toxsci/kfac122.
Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) leads to dysfunctions of human trophoblast cells and further induces miscarriage. In our previous study, we have found that lnc-HZ03 and miR-hz03 are upregulated in BPDE-exposed human trophoblast cells and in recurrent miscarriage tissues; and the upregulated miR-hz03 caused by lnc-HZ03 further promotes the apoptosis of human trophoblast cells and induces miscarriage. However, how lnc-HZ03 upregulates miR-hz03 is completely unknown. In this study, we find that lnc-HZ03 upregulates the expression level of a transcription factor TFIID (a TATA-binding protein) and promotes TFIID-mediated transactivation response element RNA-binding protein (TRBP) transcription. Subsequently, the upregulated TRBP promotes the maturation of miR-hz03 by splicing its precursor pre-miR-hz03 in human trophoblast cells. In BPDE-exposed trophoblast cells or in recurrent miscarriage tissues, lnc-HZ03 was upregulated, which accelerates the TFIID-mediated TRBP transcription and thus promotes TRBP-mediated miR-HZ03 maturation. Subsequently, the upregulated miR-hz03 further promotes the apoptosis of human trophoblast cells and induces miscarriage. This work provides new insights into the regulation of miRNA expression levels by lncRNAs in BPDE-exposed human trophoblast cells.
苯并（a）芘-7,8-二氢二醇-9,10-环氧化物（BPDE）会导致人滋养层细胞功能障碍并进一步引发流产。在我们之前的研究中，我们发现lnc-HZ03和miR-hz03在暴露于BPDE的人滋养层细胞和复发性流产组织中上调；并且由lnc-HZ03引起的上调的miR-hz03进一步促进人滋养层细胞的凋亡并导致流产。然而，lnc-HZ03如何上调miR-hz03完全未知。在本研究中，我们发现lnc-HZ03上调转录因子TFIID（一种TATA结合蛋白）的表达水平并促进TFIID介导的反式激活应答元件RNA结合蛋白（TRBP）转录。随后，上调的TRBP通过剪接其前体pre-miR-hz03促进人滋养层细胞中miR-hz03的成熟。在暴露于BPDE的滋养层细胞或复发性流产组织中，lnc-HZ03上调，这加速了TFIID介导的TRBP转录，从而促进TRBP介导的miR-HZ03成熟。随后，上调的miR-hz03进一步促进人滋养层细胞的凋亡并导致流产。这项工作为lncRNA在暴露于BPDE的人滋养层细胞中对miRNA表达水平的调控提供了新的见解。
