YY1‐PVT1 affects trophoblast invasion and adhesion by regulating mTOR pathway‐mediated autophagy

Abstract

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.

Long non-coding RNA Xist regulates oocyte loss via suppressing miR-23b-3p/miR-29a-3p maturation and upregulating STX17 in perinatal mouse ovaries

“…6G–I ). In agreement with the previous studies showing that YY1 is implicated in autophagy in multiple cells 47 , 48 , we then confirmed that YY1 positively regulated the LC3B protein expression in the newborn ovaries (Supplementary Fig. S5A ).…”

The Role of Long Non-Coding RNAs in Trophoblast Regulation in Preeclampsia and Intrauterine Growth Restriction

“…Recurrent spontaneous abortion (RSA) is a common complication of human pregnancy defined by two or more abortions before the 20th gestational week. The incidence of RSA is approximately 1–5%, with an increasing tendency in recent years [ 138 ]. RSA occurrence is associated with trophoblast insufficiency and impaired remodeling of the spiral arteries into low-resistance blood vessels.…”

“…RSA occurrence is associated with trophoblast insufficiency and impaired remodeling of the spiral arteries into low-resistance blood vessels. Yang et al has recently reported that the expression of the lncRNA-PVT1 is significantly reduced in tissues from RSA patients [ 138 ]. They also demonstrated that knockdown of lncRNA-PVT1 significantly reduced adhesion, invasion, autophagy, and mTOR expression in HTR-8/SVneo cells, which significantly increased apoptosis.…”

“…They also demonstrated that knockdown of lncRNA-PVT1 significantly reduced adhesion, invasion, autophagy, and mTOR expression in HTR-8/SVneo cells, which significantly increased apoptosis. This study further revealed a novel regulatory pathway in which Yin Yang 1 (YY1), a transcription factor involved in the regulation of trophoblast invasiveness at the maternal-fetal interface, can act directly on the lncRNA-PVT1 promoter to regulate its transcription, which further affects trophoblast invasion by regulating autophagy via the mTOR pathway [ 138 ].…”

Disruption of Placental Homeostasis Leads to Preeclampsia

“…Recently, Yin Yang 1, a transcription factor for the cytoskeleton-related proteins whose mRNA level was shown to be lower in recurrent spontaneous abortion patients, has been identified as a regulator of autophagy in trophoblasts [52,53]. In addition, Fetuin-A, an endogenous inhibitor of the insulin receptor, which increases in women with gestational diabetes mellitus, inhibits autophagy via repression of beclin1 (BECN1) [54].…”