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Objectives: This study investigated the role of circular RNAs (circRNAs) in the pathogenesis of ameloblastoma (AB), identifying potential novel targets for future targeted therapy. Materials and Methods: CircRNA and microRNA (miRNA) profiling in AB were built with microarrays. Six novel circRNAs were validated, circ‐miRNA networks were delineated. Hsa‐miR‐608 was filtered over cross‐comparison between database screening, miRNA microarray and validated. Circ‐miRNA binding sponge was validated via luciferase reporter assay. Downstream mRNAs were screened. Regulation between miRNAs and mRNAs was confirmed in vitro. Gene interaction networks and circRNA–miRNA–mRNA interaction pathway enrichment analyses were established. Results: Six differentially expressed circRNAs were selected and validated. According to miRNAs and pathways predicted, six correlated miRNAs were selected, hsa‐miR‐608 was filtered and validated. The hsa_circ_0089153/hsa‐miR‐608 binding sponge was validated. Downstream gene interaction networks showed that EGFR and p53 had the strongest co‐expression. In vitro transfection results confirmed the suppressive function of miR‐608 and EGFR p53. Hsa_circ_0089153/hsa‐miR‐608/EGFR p53 interaction pathway enrichment analysis confirmed functions mainly enriched in MAPK and related signaling pathways regulating AB progression. Conclusions: Six novel circRNAs were identified. Hsa_circ_0089153/hsa‐miR‐608 sponging was validated, hsa‐miR‐608 downregulated EGFR and p53, which might further regulate cell proliferation, differentiation, apoptosis, and cell cycle processes via the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: The environment in space could affect microorganisms by changing a variety of features, including proliferation rate, cell physiology, cell metabolism, biofilm production, virulence, and drug resistance. However, the relevant mechanisms remain unclear. To explore the effect of a space environment on Bacillus cereus, a strain of B. cereus was sent to space for 398h by ShenZhou VIII from November 1, 2011 to November 17, 2011. A ground simulation with similar temperature conditions was simultaneously performed as a control. After the flight, the flight and control strains were further analyzed using phenotypic, genomic, transcriptomic and proteomic techniques to explore the divergence of B. cereus in a space environment. The flight strains exhibited a significantly slower growth rate, a significantly higher amikacin resistance level, and changes in metabolism relative to the ground control strain. After the space flight, three polymorphic loci were found in the flight strains LCT-BC25 and LCT-BC235. A combined transcriptome and proteome analysis was performed, and this analysis revealed that the flight strains had changes in genes/proteins relevant to metabolism. In addition, certain genes/proteins that are relevant to structural function, gene expression modification and translation, and virulence were also altered. Our study represents the first documented analysis of the phenotypic, genomic, transcriptomic, and proteomic changes that occur in B. cereus during space flight, and our results could be beneficial to the field of space microbiology. [Copyright &y& Elsevier]

Treatments for triple-negative breast cancer (TNBC) are limited; intermediate-conductance calcium-activated potassium (SK4) channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC) and western blotting (WB), increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p>0.05). Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (p<0.05). Further investigation revealed that treatment with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) caused MDA-MB-231 cells to undergo the epithelial-mesenchymal transition (EMT) and to show increased SK4 mRNA expression. In addition, the down-regulation of SK4 expression inhibited the EMT markers Vimentin and Snail1. Collectively, our findings suggest that SK4 channels are expressed in TNBC and are involved in the proliferation, apoptosis, migration and EMT processes of TNBC cells. [ABSTRACT FROM AUTHOR]