Down-regulated long non-coding RNA PVT1 contributes to gestational diabetes mellitus and preeclampsia via regulation of human trophoblast cells

作者：Qiuhong Wang, Xun Lu, Chunyan Li, Wen Zhang, Yan Lv, Luyao Wang, Lan Wu, Meng Li, Yuru Fan, Hongjuan Ding, Wei Long, Mingming Lv · 发表于：Biomedicine & Pharmacotherapy · 年份：2019 · DOI：10.1016/j.biopha.2019.109501 · 被引用次数：87 · 研究领域：Pregnancy and preeclampsia studies、Gestational Diabetes Research and Management、Cancer-related molecular mechanisms research

OBJECTIVE: We aimed to explore the expression level and biological function of lncRNA PVT1 in human trophoblast cells. METHODS: The expression levels of PVT1 in cancer cell lines, HTR8/SVneo cell, HUVEC cell, the maternal placenta of GDM patients, PE patients and normal pregnancy were detected by qRT-PCR. The cell culture, cell transfection, CCK-8 assay, flow cytometry, wound scratch assay and transwell were carried out to determine the effects of silencing and overexpression of PVT1 on the HTR8/SVneo trophoblast cell line. Nuclear and chromatin RNA fraction assay, RNA-sequencing, western blot and qRT-PCR were conducted to preliminarily explore possible mechanisms. RESULTS: The relative PVT1 expression level in HTR-8/Svneo cells was higher compared to other cancer cells and HUVEC, and was lower in the GDM and PE placentas than in the normal placentas. The results showed that PVT1 knockdown notably inhibited the proliferation, migration and invasiveness abilities of trophoblast cells, and significantly promoted the apoptosis. Furthermore, overexpression of PVT1 showed the opposite results. We identified 105 differentially expressed genes after PVT1 knockdown, 23 were up-regulated and 82 were down-regulated. GO enrichment analysis and pathway enrichment analysis showed that the DEGs were closely related to the functional changes of trophoblast cells. Because of the enrichment of 7 DEGs and less Q value, PI3K/AKT pathway was prominent and attracted our attention. More importantl...