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Upregulated lnc‐HZ02 and miR‐hz02 inhibited migration and invasion by downregulating the FAK/SRC/PI3K/AKT pathway in BPDE‐treated trophoblast cells
Author(s) -
Guo Jiarong,
Li Rui,
Xu Zhongyan,
Tian Peng,
Wang Rong,
Li Youzhu,
Qiu Xia,
Zou Peng,
He Mei,
Ao Lin,
Liu Qicai,
Zhang Huidong
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22757
Subject(s) - pi3k/akt/mtor pathway , downregulation and upregulation , trophoblast , protein kinase b , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , cell migration , chemistry , signal transduction , cancer research , biology , cell , biochemistry , placenta , fetus , genetics , pregnancy , gene
Abstract 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.