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.
Yang YeSushi JiangTao DuMiao DingMinzhi HouChenyang MiTingting LiangHuan ZhongJiayu XieWenming XuHuidong ZhangXiaomiao ZhaoPublished in: Reproductive sciences (Thousand Oaks, Calif.) (2021)
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.
Keyphrases
- cell migration
- long non coding rna
- poor prognosis
- signaling pathway
- pi k akt
- induced apoptosis
- cell proliferation
- cell cycle arrest
- gene expression
- transcription factor
- oxidative stress
- human health
- risk assessment
- binding protein
- cell death
- endoplasmic reticulum stress
- high glucose
- climate change
- pregnancy outcomes
- stress induced