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https://www.readbyqxmd.com/read/28174720/netrin-1-protects-hepatocytes-against-cell-death-through-sustained-translation-during-the-unfolded-protein-response
#1
Thomas Lahlali, Marie-Laure Plissonnier, Cristina Romero-López, Maud Michelet, Benjamin Ducarouge, Alfredo Berzal-Herranz, Fabien Zoulim, Patrick Mehlen, Romain Parent
BACKGROUND & AIMS: Netrin-1, a multifunctional secreted protein, is up-regulated in cancer and inflammation. Netrin-1 blocks apoptosis induced by the prototypical dependence receptors deleted in colorectal carcinoma and uncoordinated phenotype-5. Although the unfolded protein response (UPR) triggers apoptosis on exposure to stress, it first attempts to restore endoplasmic reticulum homeostasis to foster cell survival. Importantly, UPR is implicated in chronic liver conditions including hepatic oncogenesis...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28112219/c-myb-knockdown-increases-the-neomycin-induced-damage-to-hair-cell-like-hei-oc1-cells-in-vitro
#2
Xiaoyu Yu, Wenwen Liu, Zhaomin Fan, Fuping Qian, Daogong Zhang, Yuechen Han, Lei Xu, Gaoying Sun, Jieyu Qi, Shasha Zhang, Mingliang Tang, Jianfeng Li, Renjie Chai, Haibo Wang
c-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077577/extracellular-microrna-signature-of-human-helper-t-cell-subsets-in-health-and-autoimmunity
#3
Anna Torri, Donatella Carpi, Elisabetta Bulgheroni, Maria-Cristina Crosti, Monica Moro, Paola Gruarin, Riccardo L Rossi, Grazisa Rossetti, Dolores Di Vizio, Mirjam Hoxha, Valentina Bollati, Cristina Gagliani, Carlo Tacchetti, Moira Paroni, Jens Geginat, Laura Corti, Luigia Venegoni, Emilio Berti, Massimiliano Pagani, Giuseppe Matarese, Sergio Abrignani, Paola de Candia
Upon TCR stimulation, CD4+ T lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro TCR stimulation of Th1, Th17 and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared to those released by the other subsets...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28012106/osteogenic-potential-of-the-transcription-factor-c-myb
#4
V Oralova, E Matalova, M Killinger, L Knopfova, J Smarda, M Buchtova
The transcription factor c-MYB is a well-known marker of undifferentiated cells such as haematopoietic cell precursors, but recently it has also been observed in differentiated cells that produce hard tissues. Our previous findings showed the presence of c-MYB in intramembranous bones and its involvement in the chondrogenic steps of endochondral ossification, where the up-regulation of early chondrogenic markers after c-myb overexpression was observed. Since we previously detected c-MYB in osteoblasts, we aimed to analyse the localisation of c-MYB during later stages of endochondral bone formation and address its function during bone matrix production...
December 24, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27974718/c-myb-overexpression-in-cytology-smears-of-tracheobronchial-and-pulmonary-adenoid-cystic-carcinomas
#5
Archana George Vallonthaiel, Deepali Jain, Varsha Singh, Kavneet Kaur, Karan Madan, Vinay Kumar, Venkateswaran K Iyer, Mehar Chand Sharma
AIMS: Adenoid cystic carcinoma (AdCC) is a malignant epithelial neoplasm that occurs rarely in the lower respiratory tract (LRT). AdCC at various sites is associated with the novel fusion transcript MYB-NFIB, along with the overexpression of the Myb protein. The expression of the Myb protein in AdCC of the LRT has not been evaluated much. STUDY DESIGN: Cases of AdCC of the LRT diagnosed on cytology or histology were retrieved from our institutional archives. c-Myb expression was analyzed on immunocytochemistry/immunohistochemistry (ICC/IHC) and was correlated with clinicopathological parameters...
2017: Acta Cytologica
https://www.readbyqxmd.com/read/27896869/identifying-the-location-of-epidermal-growth-factor-responsive-element-involved-in-the-regulation-of-type-iib-sodium-phosphate-cotransporter-expression-in-porcine-intestinal-epithelial-cells
#6
T Xing, X Tan, Q Yu, T Yang, R Fang
Phosphate is an important mineral nutrient for both human and animals in growth and physiological functions; thus, much effort in the past has been made to clarify the mechanisms governing its absorption. Previous studies have found that epidermal growth factor (EGF) inhibits phosphate absorption in human intestinal cells via modulating the interaction of transcriptional factor c-myb with sodium-phosphate cotransporter (NaPi-IIb) gene promoter. This finding provoked our interest in determining the effect of EGF on NaPi-IIb gene expression in intestinal cells of pigs and the location of EGF-responsive element in the gene promoter...
November 29, 2016: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/27888798/mir-103-inhibits-proliferation-and-sensitizes-hemopoietic-tumor-cells-for-glucocorticoid-induced-apoptosis
#7
Shlomit Kfir-Erenfeld, Noa Haggiag, Moshe Biton, Polina Stepensky, Nathalie Assayag-Asherie, Eitan Yefenof
Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy since they are potent inducers of lymphoid cell apoptosis. However, the development of GC resistance remains an obstacle in GC-based treatment. In the present investigation we found that miR-103 is upregulated in GC-sensitive leukemia cells treated by the hormone. Transfection of GC resistant cells with miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of GC sensitive cells rendered them partially resistant...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27765671/the-oncoprotein-hbxip-up-regulates-yap-through-activation-of-transcription-factor-c-myb-to-promote-growth-of-liver-cancer
#8
Yue Wang, Runping Fang, Ming Cui, Weiying Zhang, Xiao Bai, Huawei Wang, Bowen Liu, Xiaodong Zhang, Lihong Ye
The oncoprotein Yes-associated protein (YAP) in Hippo pathway plays crucial roles in the development of cancer. However, the mechanism of YAP regulation in cancer remains poorly understood. Here, we supposed that the oncoprotein hepatitis B X-interacting protein (HBXIP) might be involved in the modulation of YAP in liver cancer. Interestingly, our data showed that the expression levels of HBXIP were positively associated with those of YAP in clinical hepatocellular carcinoma (HCC) samples by immunohistochemistry (IHC) staining and real-time PCR assays...
January 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27707899/small-molecule-disruption-of-the-myb-p300-cooperation-targets-acute-myeloid-leukemia-cells
#9
Sagar Uttarkar, Therese Piontek, Sandeep Dukare, Caroline Schomburg, Peter Schlenke, Wolfgang E Berdel, Carsten Müller-Tidow, Thomas J Schmidt, Karl-Heinz Klempnauer
The transcription factor c-Myb is essential for the proliferation of hematopoietic cells and has been implicated in the development of leukemia and other human cancers. Pharmacologic inhibition of Myb is therefore emerging as a potential therapeutic strategy for these diseases. By using a Myb reporter cell line, we have identified plumbagin and several naphthoquinones as potent low-molecular weight Myb inhibitors. We demonstrate that these compounds inhibit c-Myb by binding to the c-Myb transactivation domain and disrupting the cooperation of c-Myb with the coactivator p300, a major driver of Myb activity...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27670114/pseudomonas-aeruginosa-infection-augments-inflammation-through-mir-301b-repression-of-c-myb-mediated-immune-activation-and-infiltration
#10
Xuefeng Li, Sisi He, Rongpeng Li, Xikun Zhou, Shuang Zhang, Min Yu, Yan Ye, Yongsheng Wang, Canhua Huang, Min Wu
MicroRNAs (miRNAs) play critical roles in various biological processes, including cell proliferation, development and host defence. However, the molecular mechanism for miRNAs in regulating bacterial-induced inflammation remains largely unclear. Here, we report that miR-301b augments pro-inflammatory response during pulmonary infection, and caffeine suppresses the effect of miR-301b and thereby augments respiratory immunity. LPS treatment or Pseudomonas aeruginosa infection induces miR-301b expression via a TLR4/MyD88/NF-κB pathway...
August 8, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27608900/mir-195-enhances-cardiomyocyte-apoptosis-induced-by-hypoxia-reoxygenation-injury-via-downregulating-c-myb
#11
C Chen, K-Y Jia, H-L Zhang, J Fu
OBJECTIVE: In this study, we explored the regulative effect of miR-195 on c-myb expression and also investigated the role of miR-195 and c-myb in cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) injury. MATERIALS AND METHODS: QRT-PCR analysis was performed to measure mature miR-195 expression. H9c2 cells were transfected for miR-195 overexpression or knockdown or c-myb overexpression using Lipofectamine 2000. The cells were subjected to H/R treatment and following flow cytometric analysis of active caspase-3 or florescent study of reactive oxygen species (ROS) generation...
August 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27607579/distal-regulation-of-c-myb-expression-during-il-6-induced-differentiation-in-murine-myeloid-progenitor-m1-cells
#12
Junfang Zhang, Bingshe Han, Xiaoxia Li, Juraj Bies, Penglei Jiang, Richard P Koller, Linda Wolff
The c-Myb transcription factor is a major regulator that controls differentiation and proliferation of hematopoietic progenitor cells, which is frequently deregulated in hematological diseases, such as lymphoma and leukemia. Understanding of the mechanisms regulating the transcription of c-myb gene is challenging as it lacks a typical promoter and multiple factors are involved. Our previous studies identified some distal regulatory elements in the upstream regions of c-myb gene in murine myeloid progenitor M1 cells, but the detailed mechanisms still remain unclear...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27606337/mcidas-and-gemc1-lynkeas-specify-embryonic-radial-glial-cells
#13
Christina Kyrousi, Maria-Eleni Lalioti, Eleni Skavatsou, Zoi Lygerou, Stavros Taraviras
Ependymal cells are multiciliated cells located in the wall of the lateral ventricles of the adult mammalian brain and are key components of the subependymal zone niche, where adult neural stem cells reside. Through the movement of their motile cilia, ependymal cells control the cerebrospinal fluid flow within the ventricular system from which they receive secreted molecules and morphogens controlling self-renewal and differentiation decisions of adult neural stem cells. Multiciliated ependymal cells become fully differentiated at postnatal stages however they are specified during mid to late embryogenesis from a population of radial glial cells...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27601730/aml-suppresses-hematopoiesis-by-releasing-exosomes-that-contain-micrornas-targeting-c-myb
#14
Noah I Hornick, Ben Doron, Sherif Abdelhamed, Jianya Huan, Christina A Harrington, Rongkun Shen, Xiaolu A Cambronne, Santhosh Chakkaramakkil Verghese, Peter Kurre
Exosomes are paracrine regulators of the tumor microenvironment and contain complex cargo. We previously reported that exosomes released from acute myeloid leukemia (AML) cells can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors. We found that the systemic loss of hematopoietic function is also in part a consequence of AML exosome-directed microRNA (miRNA) trafficking to HSPCs. Exosomes isolated from cultured AML or the plasma from mice bearing AML xenografts exhibited enrichment of miR-150 and miR-155...
September 6, 2016: Science Signaling
https://www.readbyqxmd.com/read/27566443/a-phase-ii-study-of-axitinib-ag-013736-in-patients-with-incurable-adenoid-cystic-carcinoma
#15
A L Ho, L Dunn, E J Sherman, M G Fury, S S Baxi, R Chandramohan, S Dogan, L G T Morris, G D Cullen, S Haque, C S Sima, A Ni, C R Antonescu, N Katabi, D G Pfister
BACKGROUND: Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. The majority of ACCs express the oncogenic transcription factor MYB (also c-myb), often in the context of a MYB gene rearrangement. This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC. PATIENTS AND METHODS: This is a minimax two-stage, phase II trial that enrolled patients with incurable ACC of any primary site...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27487467/the-formation-and-characteristics-of-the-i-motif-structure-within-the-promoter-of-the-c-myb-proto-oncogene
#16
Huihui Li, Jinhui Hai, Jiang Zhou, Gu Yuan
C-myb proto-oncogene is a potential therapeutic target for some human solid tumors and leukemias. A long cytosine-rich sequence, which locates the downstream of the transcription initiation site, is demonstrated to fold into an intramolecular i-motif DNA using electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy. Effects of factors, including the pH value, the number of C:C(+) dimers, the concentration of buffer, the molecular crowding condition, and the coexistence of the complementary DNA, on the formation and the structural stability of the i-motif DNA are systematically studied...
September 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27457538/c-myb-hyperactivity-leads-to-myeloid-and-lymphoid-malignancies-in-zebrafish
#17
W Liu, M Wu, Z Huang, J Lian, J Chen, T Wang, A Y H Leung, Y Liao, Z Zhang, Q Liu, K Yen, S Lin, L I Zon, Z Wen, Y Zhang, W Zhang
The c-MYB transcription factor is a key regulator of hematopoietic cell proliferation and differentiation, and dysregulation of c-MYB activity often associates with various hematological disorders. Yet, its pathogenic role remains largely unknown due to lack of suitable animal models. Here, we report a detail characterization of a c-myb-gfp transgenic zebrafish harboring c-Myb hyperactivity (named c-myb(hyper)). This line exhibits abnormal granulocyte expansion that resembles human myelodysplastic syndrome (MDS) from embryonic stage to adulthood...
January 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27348048/structured-and-unstructured-binding-of-an-intrinsically-disordered-protein-as-revealed-by-atomistic-simulations
#18
Raúl Esteban Ithuralde, Adrián Enrique Roitberg, Adrián Gustavo Turjanski
Intrinsically disordered proteins (IDPs) are a set of proteins that lack a definite secondary structure in solution. IDPs can acquire tertiary structure when bound to their partners; therefore, the recognition process must also involve protein folding. The nature of the transition state (TS), structured or unstructured, determines the binding mechanism. The characterization of the TS has become a major challenge for experimental techniques and molecular simulations approaches since diffusion, recognition, and binding is coupled to folding...
July 20, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27307595/dysregulation-of-c-myb-pathway-by-aberrant-expression-of-proto-oncogene-myb-provides-the-basis-for-malignancy-in-adult-t-cell-leukemia-lymphoma-cells
#19
Kazumi Nakano, Kaoru Uchimaru, Atae Utsunomiya, Kazunari Yamaguchi, Toshiki Watanabe
PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive human T-cell malignancy induced by human T-lymphotrophic virus-1 (HTLV-1) infection. The genetic alterations in infected cells that lead to transformation have not been completely elucidated, thus hindering the identification of effective therapeutic targets for ATL. Here, we present the first assessment of MYB proto-oncogene dysregulation in ATL and an exploration of its role in the onset of ATL. EXPERIMENTAL DESIGN: We investigated the expression patterns of MYB splicing variants in ATL...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27226027/endoplasmic-reticulum-stress-enhances-fibrosis-through-ire1%C3%AE-mediated-degradation-of-mir-150-and-xbp-1-splicing
#20
Femke Heindryckx, François Binet, Markella Ponticos, Krista Rombouts, Joey Lau, Johan Kreuger, Pär Gerwins
ER stress results in activation of the unfolded protein response and has been implicated in the development of fibrotic diseases. In this study, we show that inhibition of the ER stress-induced IRE1α signaling pathway, using the inhibitor 4μ8C, blocks TGFβ-induced activation of myofibroblasts in vitro, reduces liver and skin fibrosis in vivo, and reverts the fibrotic phenotype of activated myofibroblasts isolated from patients with systemic sclerosis. By using IRE1α(-/-) fibroblasts and expression of IRE1α-mutant proteins lacking endoribonuclease activity, we confirmed that IRE1α plays an important role during myofibroblast activation...
2016: EMBO Molecular Medicine
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