Key Laboratory of Environment and Female Reproductive Health, West China School of Public Health & West China Fourth Hospital, Sichuan University, Chengdu, China.
Department of Gynaecology and Obstetrics, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuang, China.
J Biochem Mol Toxicol. 2021 Jun;35(6):1-13. doi: 10.1002/jbt.22757. Epub 2021 Apr 14.
BPDE (benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide), a metabolite of environmental carcinogenic BaP, weakens the migration and invasion of human villous trophoblast cells and may further induce miscarriage. However, the underlying mechanisms remain largely unknown. In this study, we identified that in trophoblast Swan 71 and HTR-8/SVneo cells, miR-hz02 upregulates the level of lnc-HZ02, which inhibits the expression of an RNA-binding protein HuR. HuR could interact with FAK mRNA and promote its mRNA stability, thus upregulating the FAK level and the FAK/SRC/PI3K/AKT pathway, and finally maintaining the normal migration and invasion of trophoblast cells. If trophoblast cells are exposed to BPDE, both miR-hz02 and lnc-HZ02 are upregulated, which reduce the level of HuR, weaken the interactions of HuR with FAK mRNA, downregulate FAK level and the FAK/SRC/PI3K/AKT pathway, and finally inhibit cell migration and invasion. This study provides a novel scientific understanding of the dysfunctions of human trophoblast cells.
BPDE（苯并[a]芘-7,8-二氢二醇-9,10-环氧化物）是环境致癌物质 BaP 的代谢产物，它削弱了人绒毛滋养层细胞的迁移和侵袭能力，可能进一步导致流产。然而，其潜在机制在很大程度上尚不清楚。在本研究中，我们发现 miR-hz02 在绒癌细胞 Swan 71 和 HTR-8/SVneo 中上调了 lnc-HZ02 的水平，lnc-HZ02 抑制了 RNA 结合蛋白 HuR 的表达。HuR 可以与 FAK mRNA 相互作用并促进其 mRNA 稳定性，从而上调 FAK 水平以及 FAK/SRC/PI3K/AKT 通路，最终维持滋养层细胞的正常迁移和侵袭。如果滋养层细胞暴露于 BPDE，miR-hz02 和 lnc-HZ02 均上调，降低 HuR 水平，减弱 HuR 与 FAK mRNA 的相互作用，下调 FAK 水平以及 FAK/SRC/PI3K/AKT 通路，最终抑制细胞迁移和侵袭。本研究为理解人绒毛滋养层细胞功能障碍提供了新的科学认识。
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