MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma

<p>Abstract</p> <p>Background</p> <p>MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.</p> <p>Results</p> <p>Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.</p> <p>Conclusion</p> <p>To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.</p

Unveiling Defect-Mediated Carrier Dynamics in Monolayer Semiconductors by Spatiotemporal Microwave Imaging

The optoelectronic properties of atomically thin transition-metal dichalcogenides are strongly correlated with the presence of defects in the materials, which are not necessarily detrimental for certain applications. For instance, defects can lead to an enhanced photoconduction, a complicated process involving charge generation and recombination in the time domain and carrier transport in the spatial domain. Here, we report the simultaneous spatial and temporal photoconductivity imaging in two types of WS2 monolayers by laser-illuminated microwave impedance microscopy. The diffusion length and carrier lifetime were directly extracted from the spatial profile and temporal relaxation of microwave signals respectively. Time-resolved experiments indicate that the critical process for photo-excited carriers is the escape of holes from trap states, which prolongs the apparent lifetime of mobile electrons in the conduction band. As a result, counterintuitively, the photoconductivity is stronger in CVD samples than exfoliated monolayers with a lower defect density. Our work reveals the intrinsic time and length scales of electrical response to photo-excitation in van der Waals materials, which is essential for their applications in novel optoelectronic devices.Comment: 21 pages, 4 figure

Cyclic pressure on compression-moulded bioresorbable phosphate glass fibre reinforced composites

The use of thermoplastic composites based on poly(lactic) acid and phosphate glass fibres over metallic alloys for clinical restorative treatment is highly beneficial due to their biocompatibility and biodegradability. However, difficulties in achieving a thorough melt impregnation at high fibre contents while limiting polymer degradation is one of the main issues encountered during their manufacture. This paper reports for the first time on the effects of pressure cycling on the mechanical properties of compression moulded polylactic acid-phosphate glass fibre composites. The strength of the composites consolidated under pressure cycling were at least 30% higher than those in which conventional static pressure was used. The marked disparity was attributed to the influence of pressure cycling on the fibre preform permeability, the melt viscosity and the capillary pressure, leading to improved fibre wet-out with respect to static pressure. Implementation of a cyclic pressure appeared to promote the occurrence of transcrystallinity in the polymer matrix as suggested by DSC traces. The fibre content influenced PLA thermal degradation since the matrix molecular weight decreased as the fibre content increased on account of the moisture adsorbed by the glass surface. However, this extent of degradation did not impair the matrix mechanical performance in the composites

Phonon Renormalization in Reconstructed MoS2 Moire Superlattices

In moiré crystals formed by stacking van der Waals (vdW) materials, surprisingly diverse correlated electronic phases and optical properties can be realized by a subtle change in the twist angle. Here, we discover that phonon spectra are also renormalized in MoS2 twisted bilayers, adding a new perspective to moiré physics. Over a range of small twist angles, the phonon spectra evolve rapidly due to ultra-strong coupling between different phonon modes and atomic reconstructions of the moiré pattern. We develop a new low-energy continuum model for phonons that overcomes the outstanding challenge of calculating properties of large moiré supercells and successfully captures essential experimental observations. Remarkably, simple optical spectroscopy experiments can provide information on strain and lattice distortions in moiré crystals with nanometer-size supercells. The newly developed theory promotes a comprehensive and unified understanding of structural, optical, and electronic properties of moiré superlattices.The spectroscopy experiments at UT-Austin (J.Q.) were primarily funded by the U.S. Department of Energy, Office of Basic Energy Sciences under grant DE-SC0019398 and a grant from the University of Texas. Material preparation was funded by the Welch Foundation via grant F-1662. The collaboration between the X.L., C.S., K.L., and M.A. groups is facilitated by the NSF-MRSEC under DMR- 1720595, which funded J.C. and J.E. partially. L.L. and F.L. acknowledge support by the TU-D doctoral program of TU Wien, as well as from the Austrian Science Fund (FWF), project I-3827. The authors ac- knowledge discussions with S. Reichardt and the use of facilities and instrumentation supported by the National Science Foundation through the Center for Dynamics and Control of Materials: an NSF MRSEC under Cooperative Agreement No. DMR-1720595. P.T. acknowledges support from the National Natural Science Foundation of China (Grant No.11874350) and CAS Key Research Program of Frontier Sciences (Grant No. ZDBS-LY-SLH004). M.L. acknowledge the support from the Project funded by China Post- doctoral Science Foundation (Grant No. 2019TQ0317). The PFM work (D.L. and K.L.) was supported by NSF DMR-2004536 and Welch Foundation Grant F-1814. K.W. and T.T. acknowledge support from the Elemental Strategy Initiative conducted by the MEXT, Japan, Grant Number JPMXP0112101001, JSPS KAKENHI Grant Numbers JP20H00354 and the CREST(JPMJCR15F3), JST.Center for Dynamics and Control of Material

NOXA-Induced Alterations in the Bax/Smac Axis Enhance Sensitivity of Ovarian Cancer Cells to Cisplatin

Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy