YY1‐PVT1 affects trophoblast invasion and adhesion by regulating mTOR pathway‐mediated autophagy
YY1‐PVT1 affects trophoblast invasion and adhesion by regulating mTOR pathway‐mediated autophagy
复制标题
DOI：
10.1002/jcp.29560
复制
发表时间：
2020-01
影响因子：
5.6
通讯作者：
Dongyong Yang;Jinli Ding;Yanqing Wang;Mengqin Yuan;Shu Xian;Li Zhang;Shiyi Liu;Fangfang Dai
中科院分区：
文献类型：
--
作者：
Dongyong Yang;Jinli Ding;Yanqing Wang;Mengqin Yuan;Shu Xian;Li Zhang;Shiyi Liu;Fangfang Dai
滋养细胞侵袭不足是复发性自然流产（RSA）发生的关键因素。我们之前的研究发现阴阳1 （YY1）是一个参与母胎界面滋养细胞侵袭调节的转录因子。长链非编码rna （lncRNAs）可以通过多种方式调节基因表达和自噬。本研究旨在探讨YY1与lncRNAs的关系，以及lncRNAs影响滋养层细胞生物学行为的机制。生物信息学分析预测YY1在浆细胞瘤变异易位1 （PVT1）启动子区有3个结合位点。染色质免疫沉淀实验和电泳迁移转移实验证实YY1可以直接结合PVT1启动子。与正常妊娠组人胎盘绒毛组织样本中PVT1的表达水平相比，RSA组PVT1的表达水平明显降低。PVT1敲低显著降低HTR‐8/SVneo细胞的粘附、侵袭、自噬和mTOR表达，并显著增加体外凋亡。本研究揭示了一种新的调控途径，YY1可直接作用于PVT1启动子调控其转录，进而通过mTOR途径调控自噬进而影响滋养细胞侵袭和粘附，这些作用可能与RSA发病机制有关。
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.