56 research outputs found

    MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1

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    <p>Abstract</p> <p>Background</p> <p>Epithelial-mesenchymal transition (EMT) is the key process driving cancer metastasis. Oncogene/self renewal factor BMI-1 has been shown to induce EMT in cancer cells. Recent studies have implied that noncoding microRNAs (miRNAs) act as crucial modulators for EMT. The aims of this study was to determine the roles of BMI-1 in inducing EMT of endometrial cancer (EC) cells and the possible role of miRNA in controlling BMI-1 expression.</p> <p>Methods and results</p> <p>We evaluated the expression of BMI-1 gene in a panel of EC cell lines, and detected a strong association with invasive capability. Stable silencing of BMI-1 in invasive mesenchymal-type EC cells up-regulated the epithelial marker E-cadherin, down-regulated mesenchymal marker Vimentin, and significantly reduced cell invasion <it>in vitro</it>. Furthermore, we discovered that the expression of BMI-1 was suppressed by miR-194 via direct binding to the BMI-1 3'-untranslated region 3'-UTR). Ectopic expression of miR-194 in EC cells induced a mesenchymal to epithelial transition (MET) by restoring E-cadherin, reducing Vimentin expression, and inhibiting cell invasion <it>in vitro</it>. Moreover, BMI-1 knockdown inhibited <it>in vitro </it>EC cell proliferation and clone growth, correlated with either increased p16 expression or decreased expression of stem cell and chemoresistance markers (SOX-2, KLF4 and MRP-1).</p> <p>Conclusion</p> <p>These findings demonstrate the novel mechanism for BMI-1 in contributing to EC cell invasion and that repression of BMI-1 by miR-194 could have a therapeutic potential to suppress EC metastasis.</p

    Self-Turn-on-Free 5V Gate Driving for 1200V Scaled IGBT

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    Negative biasing of the gate voltage in a scaled insulated gate bipolar transistor (IGBT) during the off-state was modeled and found to be effective against self-turn-on failures. The required self-turn-on-free criteria were verified experimentally.31st IEEE International Symposium on Power Semiconductor Devices and ICs (ISPSD 2019), 19-23 May 2019, Shanghai, Chin

    A Substellar Companion to Pleiades HII 3441

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    We find a new substellar companion to the Pleiades member star, Pleiades HII 3441, using the Subaru telescope with adaptive optics. The discovery is made as part of the high-contrast imaging survey to search for planetary-mass and substellar companions in the Pleiades and young moving groups. The companion has a projected separation of 0".49 +/- 0".02 (66 +/- 2 AU) and a mass of 68 +/- 5 M_J based on three observations in the J-, H-, and K_S-band. The spectral type is estimated to be M7 (~2700 K), and thus no methane absorption is detected in the H band. Our Pleiades observations result in the detection of two substellar companions including one previously reported among 20 observed Pleiades stars, and indicate that the fraction of substellar companions in the Pleiades is about 10.0 +26.1/-8.8 %. This is consistent with multiplicity studies of both the Pleiades stars and other open clusters.Comment: Main text (14 pages, 4 figures, 4 tables), and Supplementary data (8 pages, 3 tables). Accepted for Publications of Astronomical Society of Japa

    Indications of M-Dwarf Deficits in the Halo and Thick Disk of the Galaxy

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    We compared the number of faint stars detected in deep survey fields with the current stellar distribution model of the Galaxy and found that the detected number in the H band is significantly smaller than the predicted number. This indicates that M-dwarfs, the major component, are fewer in the halo and the thick disk. We used archived data of several surveys in both the north and south field of GOODS (Great Observatories Origins Deep Survey), MODS in GOODS-N, and ERS and CANDELS in GOODS-S. The number density of M-dwarfs in the halo has to be 20 +/- 13% relative to that in the solar vicinity, in order for the detected number of stars fainter than 20.5 mag in the H band to match with the predicted value from the model. In the thick disk, the number density of M-dwarfs must be reduced (52 +/- 13%) or the scale height must be decreased (approximately 600 pc). Alternatively, overall fractions of the halo and thick disks can be significantly reduced to achieve the same effect, because our sample mainly consists of faint M-dwarfs. Our results imply that the M-dwarf population in regions distant from the Galactic plane is significantly smaller than previously thought. We then discussed the implications this has on the suitability of the model predictions for the prediction of non-companion faint stars in direct imaging extrasolar planet surveys by using the best-fit number densities

    A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production

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    The Psmb11-encoded β5t subunit of the thymoproteasome, which is specifically expressed in cortical thymic epithelial cells (cTECs), is essential for the optimal positive selection of functionally competent CD8+ T cells in mice. Here, we report that a human genomic PSMB11 variation, which is detectable at an appreciable allele frequency in human populations, alters the β5t amino acid sequence that affects the processing of catalytically active β5t proteins. The introduction of this variation in the mouse genome revealed that the heterozygotes showed reduced β5t expression in cTECs and the homozygotes further exhibited reduction in the cellularity of CD8+ T cells. No severe health problems were noticed in many heterozygous and 5 homozygous human individuals. Long-term analysis of health status, particularly in the homozygotes, is expected to improve our understanding of the role of the thymoproteasome-dependent positive selection of CD8+ T cells in humans
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