YY1/ITGA3 pathway may affect trophoblastic cells migration and invasion ability.

Recurrent spontaneous abortion (RSA) is a disturbing pregnancy disorder experienced by ~2.5% of women attempting to conceive. The pathogenesis of RSA is still unclear. Previous findings revealed that transcription factor YIN-YANG 1(YY1) was related to the pathogenesis of RSA by influence trophoblastic cell invasion ability. Present study aimed to investigate more specific molecular mechanism of YY1 playing in trophoblastic cells. In our research, RNA-seq and Chip-seq were used to find significant changed genes between si-YY1(Knock down of YY1) HTR-8/SVneo cells(n = 3) and HTR-8/SVneo cells(n = 3). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results suggested that Integrins related pathway maybe necessary to biological functions of trophoblastic cells. Chip-seq dataset analysis results predict YY1 can regulate ITGA3/7 expression by binding to the promoter region of ITGA3/7. Furthermore, results from chip experiment, RT-PCR, Dual-luciferase reporter gene assay showed that YY1 was able to bind to the promoter region of ITGA3 and regulate ITGA3 mRNA and protein expression. However, ITGA7 could not be significant influenced by YY1. Besides, gene silencing experiment, Western blot and Immunofluorescence assay confirmed that both YY1 and ITGA3 can accelerate phosphorylation focal adhesion kinase and affect cytoskeleton formation in HTR-8/SVneo cells. In conclusion, YY1/ITGA3 play a critical role in trophoblast invasion ability by regulating cytoskeleton formation.

Effect of arsenic trioxide on cervical cancer and its mechanisms.

Cervical cancer is one of the most common types of gynecological tumor, and thus identifying complementary or substitute treatment methods to treat cervical cancer is important. The present study aimed to evaluate the effect of arsenic trioxide (ATO), a traditional Chinese medicine, on cervical cancer cells and its underlying mechanism. MTT, colony formation and Transwell assays were performed to investigate the effects of different concentrations of ATO on cell proliferation and invasion, respectively. Western blotting and reverse transcription-quantitative PCR were applied to measure hypoxia-inducible factor-1α expression (HIF-1α) expression following ATO treatment. Finally, the effects of HIF-1α knockdown on cervical cancer cell proliferation, apoptosis and invasion were evaluated. The results demonstrated that ATO could inhibit cell proliferation and invasion. Moreover, ATO could induce reactive oxygen species production in a time- and dose-dependent manner. ATO could also promote the apoptosis of cervical cancer cells via HIF-1α. Therefore, the present study may provide a theoretical basis for identifying effective molecular targets for the prevention and treatment of cervical cancer.

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

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.