Research advances of polycomb group proteins in regulating mammalian development.

Polycomb group (PcG) proteins are a subset of epigenetic factors that are highly conserved throughout evolution. In mammals, PcG proteins can be classified into two muti-proteins complexes: Polycomb repressive complex 1 (PRC1) and PRC2. Increasing evidence has demonstrated that PcG complexes play critical roles in the regulation of gene expression, genomic imprinting, chromosome X-inactivation, and chromatin structure. Accordingly, the dysfunction of PcG proteins is tightly orchestrated with abnormal developmental processes. Here, we summarized and discussed the current knowledge of the biochemical and molecular functions of PcG complexes, especially the PRC1 and PRC2 in mammalian development including embryonic development and tissue development, which will shed further light on the deep understanding of the basic knowledge of PcGs and their functions for reproductive health and developmental disorders.

Metformin exhibits its therapeutic effect in the treatment of pre-eclampsia via modulating the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways.

Metformin (Met) has been found to modify the methylation of H19 and to alter its expression. In addition, IL-27, one of the downstream factors in the H19 signaling pathway, plays an important role in the pathogenesis of pre-eclampsia (PE). In this study, we investigated the molecular mechanism underlying the therapeutic effect of Met in the management of PE both in vivo and in vitro. The role of H19 signaling pathway in PE was validated using online bioinformatics tools, luciferase assays, real-time PCR and Western Blot. A tail-cuff method was used to examine the blood pressures in PE rats with or without Met treatment. Cells exhibited a dose-dependent increase of H19 methylation, which inhibited the expression of H19. Additionally, upon the Met treatment, levels of miR-148-5p and miR-216-3p were both elevated in a dose-dependent manner while levels of p28 mRNA and EBI3 mRNA were both inhibited by Met treatment. Also, H19 was found to regulate the expression of miR-148a-5p and miR-216-3p, while P28 and EBI3 were respectively identified as target genes of miR-148a-5p and miR-216-3p. Therefore, the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways were implicated in the pathogenesis of PE. Met was implicated in the pathogenesis of PE via modulating the H19 signaling pathway. The methylation of H19 reduced H19 expression, which in turn could up-regulate the expression of miR-148-5p/miR-216-3p. And the expressions of subunits of IL-27, P28 and EBI3, were thus suppressed. Therefore, Met-induced inhibition of H19 also led to the reduction of IL-27 expression, TNF-α and IL-6 in vivo.

Downregulation of α7 nicotinic acetylcholine receptors in peripheral blood monocytes is associated with enhanced inflammation in preeclampsia.

BACKGROUND: Preeclampsia is associated with chronic inflammation. The cholinergic anti-inflammatory pathway regulates systemic inflammation through activating α7 nicotinic acetylcholine receptors (α7nAChR) expressed in monocytes/macrophages. This study aimed to investigate the role of α7nAChR in peripheral blood monocytes in preeclampsia. METHODS: Peripheral blood monocytes were isolated from 30 nonpregnant (NP), 32 normotensive pregnant (NT), and 35 preeclamptic (PE) women. RESULTS: We found that both protein and mRNA expression levels of α7nAChR in monocytes from the PE women were significantly lower than those of the NP and NT women (both p < 0.01). α7nAChR protein expression levels in monocytes were negatively correlated with levels of systolic blood pressure (r = - 0.40, p = 0.04), proteinuria (r = - 0.54, p < 0.01), tumor necrosis factor-alpha (TNF-α, r = - 0.42, p = 0.01), and interleukin (IL)-1ß (r = - 0.56, p < 0.01), while positively correlated with IL-10 levels (r = 0.43, p = 0.01) in the PE women. Both baseline and lipopolysaccharides (LPS)-induced increase of TNF-α, IL-1ß, and IL-6 levels from monocytes were higher in the PE group than the NP and NT groups (all p < 0.01), but IL-10 levels in the PE group was lower than that of the NP and NT groups (p < 0.01). In addition, the NF-κB activity in monocytes from the PE women was higher than the NP and NT women (p < 0.01). Importantly, activation of α7nAChR with its agonist PNU-282987 inhibited NF-κB, decreased TNF-α, IL-1ß, and IL-6 release, and increased IL-10 release in monocytes from the PE women (all p < 0.01). CONCLUSION: In conclusion, these findings suggest that downregulation of α7nAChR may be associated with the development of preeclampsia through increasing pro-inflammatory and decreasing anti-inflammatory cytokine release via the NF-κB pathway.

Long noncoding RNA lncARSR promotes epithelial ovarian cancer cell proliferation and invasion by association with HuR and miR-200 family.

Epithelial ovarian cancer (EOC) is the fifth leading cause of female cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators in various biological processes through diverse mechanisms. Recently, lncRNA Activated in RCC with Sunitinib Resistance (lncARSR) has been reported to be upregulated and involved in sunitinib resistance of renal cell carcinoma cells. However, the functional roles in EOC have not yet been explored. In the current study, we detected the expression levels of lncARSR in 76 paired EOC tissues and adjacent normal tissues, and observed that lncARSR expression was significantly increased in EOC tissues and correlated with FIGO stage, histological grade, lymph nodes metastasis and worse survival. Loss- and gain-of-function assays demonstrated that lncARSR promoted EOC cell proliferation and invasion. Further investigations showed that lncARSR interacted with HuR, upregulated ß-catenin expression and then activated Wnt/ß-catenin signaling pathway to regulate cell proliferation. Moreover, lncARSR increased ZEB1 and ZEB2 expression by competitively binding the miR-200 family to induce EMT and invasion. Our findings suggest that the lncARSR may provide a novel therapeutic strategy for EOC treatment.