Lnc-HZ03 promotes TRBP-mediated splicing of pre-miR-hz03 to generate miR-hz03 in human trophoblast cells. (23rd December 2022)

• Record Type: Journal Article
• Authors: Zhao, Jingsong; Cheng, Liqin; Liu, Qicai; Liang, Tingting; Xie, Jiayu; Wang, Rong; Chen, Weina; Ao, Lin; Zhang, Huidong
• Is Part Of: Toxicological sciences. Volume 191:Number 2(2023)
• Page Start: 332
• Page End: 342
• Publication Date: 2022-12-23
• Subjects: BPDE -- miscarriage -- lnc-HZ03 -- miR-hz03 -- human trophoblast -- TRBP; Toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology; Periodicals; 615.9
• DOI: 10.1093/toxsci/kfac122
• Languages: English
• ISSNs: 1096-6080

Abstract

Abstract: 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.