Environmental Pollutant Benzo[a]pyrene Upregulated Long Non-coding RNA HZ07 Inhibits Trophoblast Cell Migration by Inactivating PI3K/AKT/MMP2 Signaling Pathway in Recurrent Pregnancy Loss
Environmental Pollutant Benzo[a]pyrene Upregulated Long Non-coding RNA HZ07 Inhibits Trophoblast Cell Migration by Inactivating PI3K/AKT/MMP2 Signaling Pathway in Recurrent Pregnancy Loss
复制标题
环境污染物苯并[a]芘上调长非编码 RNA HZ07 通过失活 PI3K/AKT/MMP2 信号通路抑制复发性流产中滋养层细胞迁移
DOI：
10.1007/s43032-021-00630-2
复制
发表时间：
2021-05-28
影响因子：
2.9
通讯作者：
Zhao, Xiaomiao
中科院分区：
文献类型：
--
作者：
Ye, Yang;Jiang, Sushi;Zhao, Xiaomiao
苯并（a）芘（BaP）是一种普遍存在的环境内分泌干扰物，已知对生殖具有毒性作用。然而，苯并[a]芘及其代谢产物苯并[a]芘-7，8-二醇-9，10-环氧化物（BPDE）如何诱导反复妊娠丢失（RPL）的潜在机制仍不清楚。在这项研究中，我们鉴定了一种新的长非编码RNA（lnc-HZ 07，NCBI MT 936329），其在暴露于BPDE后在滋养层细胞中上调，并且lnc-HZ 07在RPL绒毛组织中的表达显著高于对照绒毛组织。lnc-HZ 07的敲低促进滋养层细胞迁移，而lnc-HZ 07的过表达抑制滋养层细胞迁移。进一步的研究表明，lnc-HZ 07通过AKT的去磷酸化下调基质金属蛋白酶2（MMP 2）的表达来抑制滋养细胞迁移。这些结果证明了一种新的调节途径，其中BaP通过上调lnc-HZ 07下调AKT磷酸化并抑制MMP 2表达，表明lnc-HZ 07可被认为是BaP诱导的RPL的潜在病理标志物和该疾病的治疗靶点。
Benzo(a)pyrene (BaP) is a ubiquitous environmental endocrine-disrupting chemical that is known to have toxic effects on reproduction. However, the underlying mechanisms describing how BaP and its metabolite benzo[a]pyrene-7, 8-diol-9, 10-epoxide (BPDE) induce recurrent pregnancy loss (RPL) are still largely unclear. In this study, we identified a novel long non-coding RNA (lnc-HZ07, NCBI MT936329) that was upregulated in trophoblast cells after exposure to BPDE, and lnc-HZ07 expression was significantly higher in RPL villous tissues than that in control villous tissues. Knockdown of lnc-HZ07 promoted trophoblast cell migration, whereas overexpression of lnc-HZ07 inhibited trophoblast cell migration. Further study showed that lnc-HZ07 inhibited trophoblast migration by downregulating matrix metalloproteinase 2 (MMP2) expression via dephosphorylation of AKT. These results demonstrated a novel regulatory pathway in which BaP downregulated AKT phosphorylation and inhibited MMP2 expression by upregulating lnc-HZ07, suggesting that lnc-HZ07 could be considered as a potential pathological marker of BaP-induced RPL and therapeutic target for this disease.