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Owing to high mortality rate, ovarian cancer seriously threatens women’s health. Extensive abdominal metastasis and chemoresistance are the leading causes of ovarian cancer deaths. Through lncRNA sequencing, our previous study identified lncRNA SLC25A21-AS1, which was significantly downregulated in chemoresistant ovarian cancer cells. In this study, we aimed to evaluate the role and mechanism of SLC25A21-AS1 in ovarian cancer. The expression of SLC25A21-AS1 was analyzed by qRT-PCR and online database GEPIA. The biological functions of SLC25A21-AS1 and KCNK4 were analyzed by CCK-8, transwell, and flow cytometry. The specific mechanism was analyzed by RNA-sequencing, RNA binding protein immunoprecipitation, rescue experiments, and bioinformatic analysis. SLC25A21-AS1 was decreased in ovarian cancer tissues and cell lines. Overexpression of SLC25A21-AS1 enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin, and inhibited cell proliferation, invasion, and migration, while SLC25A21-AS1-silencing showed the opposite effect. Potassium channel subfamily K member 4 (KCNK4) was significantly up-regulated upon enforced expression of SLC25A21-AS1. Overexpression of KCNK4 inhibited cell proliferation, invasion, migration ability, and enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin. Meanwhile, KNCK4-overexpression rescued the promotive effect of SLC25A21-AS1-silencing on cell proliferation, invasion and migration. In addition, SLC25A21-AS1 could interact with the transcription factor Enhancer of Zeste Homolog 2 (EZH2), while EZH2 knockdown increased the expression of KCNK4 in some of the ovarian cancer cell lines. SLC25A21-AS1 enhanced the chemosensitivity and inhibited the proliferation, migration, and invasion ability of ovarian cancer cells at least partially by blocking EZH2-mediated silencing of KCNK4. [ABSTRACT FROM AUTHOR]

To deeply analyze the alterations of cervical canal microbiota in intrauterine adhesion (IUA) patients and microbiota's relation to intrauterine adhesion (IUA) severity, we prospectively enrolled 23 consecutive patients diagnosed with mild-to-severe IUA and 8 women with infertility, 3 women with submucous myomas, or 8 women with endometrial polyps, but without IUA, as non_IUA subjects. For deep grouping analysis, these enrolled women were divided into six groups, two groups, and four groups respectively. Cervical mucus was drawn from the cervical canal of each participant. The bacterial composition was identified by 16S rDNA high-throughput sequencing. For analysis of six groups, mild IUA patients had similar cervical canal microbiota diversity and composition with submucous myomas patients. Compared with mild IUA participants, patients with moderate or severe IUA had a significantly lower diversity of bacteria and higher load of Firmicutes. For analysis of two groups, IUA patients had a significantly lower diversity of bacteria and higher load of Firmicutes than non_IUA subjects. KEGG pathway function analysis showed that metabolic pathways, biosynthesis of secondary metabolites, and microbial metabolism in diverse environments were mostly enriched for these cervical canal microbiota in all enrolled patients. The severity of IUA was associated with the altered abundance of phylum Firmicutes/Acinetobacteria or genus Lactobacillus/Gardnerella in the cervical canal. Higher bacterial load but less diversity in the cervical canal may be related with the severity of IUA. The function of these cervical canal microbiota were mostly involved in metabolic pathways. [ABSTRACT FROM AUTHOR]

Concentration gradients of ECM proteins play active roles in many areas of cell biology including wound healing and metastasis. They may also form the basis of tissue engineering scaffolds, as these can direct cell adhesion and migration and promote new matrix synthesis. To better understand cell-matrix interactions on attractive gradients, we have used multiphoton excited (MPE) photochemistry to fabricate covalently linked micro-structured gradients from fibronectin (FN). The gradient design is comprised of a parallel series of individual linear gradients with overall dimensions of approximately 800 × 800 µm, where a linear dynamic range of nearly 10-fold in concentration was achieved. The adhesion dynamics of 3T3 fibroblasts were investigated, where the cell morphology and actin cytoskeleton became increasingly elongated and aligned with the direction of the gradient at increasing protein concentration. Moreover, the cell morphologies are distinct when adhered to regions of differing FN concentration but with similar topography. These results show that the fabrication approach allows investigating the roles of contact guidance and ECM cues on the cell-matrix interactions. We suggest this design overcomes some of the limitations with other fabrication methods, especially in terms of 3D patterning capabilities, and will serve as a new tool to study cell-matrix interactions. [ABSTRACT FROM AUTHOR]