MicroRNA-3935 promotes human trophoblast cell epithelial-mesenchymal transition through tumor necrosis factor receptor-associated factor 6/regulator of G protein signaling 2 axis.

BACKGROUND: Insufficient migration and invasion during trophoblast epithelial-mesenchymal transition (EMT) results in the occurrence and development of preeclampsia (PE), and our previous study has screened 52 miRNAs, whose expression levels are altered in the placental samples from PE patients, compared with the normal group. Among those, miR-3935 is one of the miRNAs being most significantly down-regulated, indicating its involvement in PE. However, the exact effect and molecular mechanisms remain unknown. METHODS: In the present study, we investigate the roles and underlying mechanisms of miR-3935 in trophoblast EMT by use of the human extra-villous trophoblast cell line HTR-8/SVneo as well as human placental tissues and maternal blood samples obtained from 15 women with normal pregnancies and 15 women with PE. Experimental methods include transfection, quantitative reverse transcription-PCR (qRT-PCR), western blot, immunofluorescence staining, dual-luciferase assays, in vitro invasion and migration assays, RNA-Seq analysis, bisulfite sequencing and immunohistochemistry staining. RESULTS: MiR-3935 expression is significantly decreased in both placentas and peripheral blood specimens of PE, and functionally, miR-3935 promotes EMT of trophoblast cells. Mechanistically, TRAF6 is identified to be a direct target of miR-3935 and TRAF6 exerts its negative effect on EMT of trophoblast cells by inhibition of RGS2, which down-regulates the methylation status of promoter of CDH1 gene that encodes E-Cadherin protein through induction of ALKBH1, resulting in increase of E-Cadherin and subsequently insufficient trophoblast EMT. CONCLUSIONS: Together these results uncover a hitherto uncharacterized role of miR-3935/TRAF6/RGS2 axis in the function of human trophoblasts, which may pinpoint the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for such obstetrical diseases as PE.

Circ-0001068 is a novel biomarker for ovarian cancer and inducer of PD1 expression in T cells.

Ovarian cancer is a primary gynecological malignancy with a global 5-year survival rate of 44%. The majority of patients present with advanced disease at initial diagnosis because of the lack of an effective early detection screening test. Circular RNAs (circRNAs) within exosomes in the circulatory system are effective diagnostic and therapeutic biomarkers for many diseases, especially tumors. In this study, we used microarrays to identify 6 circRNAs that were upregulated and 37 circRNAs that were downregulated in exosomes from ovarian cancer patients as compared to healthy volunteers. We validated the accumulation trends for the 6 upregulated circRNAs in the training set using qRT-PCR and found that circ-0001068 was significantly higher in the serum exosomes from the ovarian cancer patients as than healthy volunteers. Circ-0001068 was next evaluated further in a larger cohort. As with the training set, results from the larger cohort revealed that levels of circ-0001068 in the exosomes were significantly higher in ovarian cancer patients than healthy volunteers. Circ-0001068 was also delivered into T cells and induced PD1 expression by acting as a competing endogenous RNA (ceRNA) for miR-28-5p through the exosomes.

Draft genome sequence of a multidrug-resistant OXA-23-producing Acinetobacter baumannii ST191 clinical isolate from China.

Acinetobacter baumannii has emerged worldwide as a dominant pathogen in nosocomial infections. In this study, we report the draft genome sequence of a clinical multidrug-resistant (MDR) A. baumannii ST191 (CC92) strain. Whole-genome sequencing of the isolate was performed using an Illumina HiSeq™ 2500 system, and bioinformatics analysis was also performed. The draft genome length was 4,259,210bp, harbouring 14 gene sequences relevant to antibiotic resistance. Antimicrobial susceptibility testing revealed that the isolate was resistant to all of the tested antibiotics except for tigecycline and colistin. These data will facilitate further understanding of the genomic and resistance features of MDR A. baumannii.

MicroRNA-20b inhibits trophoblast cell migration and invasion by targeting MMP-2.

Insufficient trophoblast migration/invasion is associated with the preeclampsia (PE) development. Recently, microRNAs (miRNAs) have been confirmed to be involved in the pathogenesis of PE. The aim of the present study was to evaluate whether miRNAs is involved in the procession of PE by regulating the migration/invasion of trophoblast. First, we compared the expression profiles of miRNAs between normal and preeclamptic placentas using microarray. Validation analysis of miR-20b level in placentas and peripheral blood specimens was performed using quantitative reverse transcription PCR (qRT-PCR). Then, the effects of miR-20b on trophoblast cell migration and invasion were evaluated using wound healing assay and transwell migration assay. Further bioinformatics analysis, luciferase reporter assays and Western blot were performed to identify its target genes. The correlation between miR-20b and matrix metalloproteinase-2 (MMP-2) in placentas was determined by Pearson's correlation coefficient. Finally, HTR8/SVneo cells were co-transfected with miR-20b inhibitor and si-MMP-2 to explore the molecular mechanism by which miR-20b functions in the trophoblast migration/invasion. We found that miR-20b was elevated in placentas and peripheral blood specimens from preeclampsia patients. Further results show that overexpression of miR-20b significantly inhibited the invasiveness of human trophoblast cells, whereas miR-20b knockdown enhanced trophoblast cell invasion. Matrix metalloproteinase-2 (MMP-2), the most common enzymes in remodeling extracellular matrix components for metastasis, was proved to be a direct target of miR-20b. Inhibition of MMP-2 by siRNA could reverse the promoting effect of miR-20b inhibition on the invasion of trophoblast cells. Taken together, our study indicates that miR-20b inhibited trophoblastic invasion by targeting MMP2. The miR-20b/MMP-2 axis may provide novel insights into understanding the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for PE.