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YY1‐PVT1 affects trophoblast invasion and adhesion by regulating mTOR pathway‐mediated autophagy
Author(s) -
Yang Dongyong,
Ding Jinli,
Wang Yanqing,
Yuan Mengqin,
Xian Shu,
Zhang Li,
Liu Shiyi,
Dai Fangfang,
Wang Feiyan,
Zheng Yajing,
Zhao Xin,
Liao Shujie,
Cheng Yanxiang
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29560
Subject(s) - autophagy , biology , trophoblast , microbiology and biotechnology , transcription factor , pi3k/akt/mtor pathway , gene knockdown , chromatin immunoprecipitation , pvt1 , cell adhesion , promoter , cancer research , long non coding rna , genetics , gene expression , gene , signal transduction , apoptosis , downregulation and upregulation , cell , placenta , pregnancy , fetus
Insufficient trophoblast invasion is the key factor for the occurrence of recurrent spontaneous abortions (RSA). Our previous studies identified Yin Yang 1 (YY1) as a transcription factor involved in the regulation of trophoblast invasiveness at the maternal–fetal interface. Long noncoding RNAs (lncRNAs) can regulate gene expression and autophagy in many ways. The purpose of this study was to explore the relationship between YY1 and lncRNAs and the mechanism by which lncRNAs affect the biological behavior of trophoblasts. Bioinformatic analysis predicted that YY1 had three binding sites in the plasmacytoma variant translocation 1 (PVT1) promoter region. Chromatin immunoprecipitation experiments and electrophoretic mobility shift assays verified that YY1 can directly bind to the PVT1 promoter. Compared with its expression levels in human placental villi tissue samples from the normal pregnancy group, the PVT1 expression levels were significantly lower in tissues from the RSA group. PVT1 knockdown significantly reduced adhesion, invasion, autophagy, and mTOR expression in HTR‐8/SVneo cells and greatly increased apoptosis in vitro. This study revealed a novel regulatory pathway in which YY1 can act directly on PVT1 promoter to regulate its transcription, which further affects trophoblast invasion and adhesion by regulating autophagy via the mTOR pathway, and these effects might be involved in RSA pathogenesis.