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https://www.readbyqxmd.com/read/29679610/mutated-mitf-e87r-in-melanoma-enhances-tumor-progression-via-s100a4
#1
Alice Nordlinger, Shani Dror, Abdel Elkahloun, Justine Del Rio, Elisa Stubbs, Tami Golan, Hagar Malcov, Todd D Pricket, Julia C Cronin, Shivang Parikh, Sapir Labes, Laetitia Thomas, Gal Yankovitz, Yuval Tabach, Carmit Levy, Yardena Samuels, Mehdi Khaled
Melanoma, a melanocyte origin neoplasm, is the most lethal type of skin cancer and incidence is increasing. Several familial and somatic mutations have been identified in the gene encoding the melanocyte lineage master regulator, microphthalmia-associated transcription factor (MITF); however, the neoplastic mechanisms of these mutant MITF variants are mostly unknown. Here, by performing unbiased analysis of the transcriptomes in cells expressing mutant MITF, we identified calcium-binding protein S100A4, as a downstream target of MITF-E87R...
April 18, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29665239/fbxw7-regulates-a-mitochondrial-transcription-program-by-modulating-mitf
#2
Franco Abbate, Brateil Badal, Karen Mendelson, Iraz Toprak Aydin, Madhavika N Serasinghe, Ramiz Iqbal, Jarvier Mohammed, Alexander Solovyov, Benjamin D Greenbaum, Jerry E Chipuk, Julide Tok Celebi
FBXW7 is well characterized as a tumor suppressor in many human cancers including melanoma; however, the mechanisms of tumor suppressive function have not been fully elucidated. We leveraged two distinct RNA sequencing datasets: human melanoma cell lines (n=10) with control versus silenced FBXW7 and a cohort of human melanoma tumor samples (n=51) in order to define the transcriptomic fingerprint regulated by FBXW7. Here, we report that loss of FBXW7 enhances a mitochondrial gene transcriptional program that is dependent on MITF in human melanoma and confers poor patient outcomes...
April 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29661845/lysosome-enlargement-during-inhibition-of-the-lipid-kinase-pikfyve-proceeds-through-lysosome-coalescence
#3
Christopher H Choy, Golam Saffi, Matthew A Gray, Callen Wallace, Roya M Dayam, Zhen-Yi A Ou, Guy Lenk, Rosa Puertollano, Simon C Watkins, Roberto J Botelho
Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing and instructing cells on their metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5-bisphosphate to modulate lysosome function. PIKfyve inhibition leads to impaired degradative capacity, ion dysregulation, abated autophagic flux, and a massive enlargement of lysosomes. Collectively, this leads to various physiological defects including embryonic lethality, neurodegeneration and overt inflammation...
April 16, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29642438/sesamol-inhibited-melanogenesis-by-regulating-melanin-related-signal-transduction-in-b16f10-cells
#4
Po-Yuan Wu, Ya-Jhen You, Yi-Jung Liu, Chien-Wei Hou, Chin-Sheng Wu, Kuo-Ching Wen, Chien-Yih Lin, Hsiu-Mei Chiang
Melanin is synthesized through a series of interactions catalyzed by melanogenic enzymes such as tyrosinase, dopachrome tautomerase (tyrosinase-related protein-2; TRP-2), and tyrosinase-related protein-1 (TRP-1). Tyrosinase plays a key role in catalysing the initial and limiting steps of melanogenesis. The melanin that results from melanogenesis has the protective effect of absorbing ultraviolet radiation. However, overproduction of melanin, in addition to altering the appearance of skin, may lead to skin disorders such as melasma, solar lentigo, and postinflammatory hyperpigmentation...
April 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29630160/wardenburg-syndrome-type-2-in-a-woman-with-no-genomic-mutation-commonly-associated-with-the-syndrome
#5
Audrey Rutherford, Donald A Glass Ii, Nnenna G Agim
Waardenburg Syndrome (WS) is a condition characterized by pigmentary changes of the hair or skin, hearing loss, heterochromia iridis, and dystopia canthorum. There are four main types of WS, which can be commonly caused by mutations in the PAX3, MITF, EDNRB, EDN3, SNAI2, or SOX10 genes. Herein, we present a patient with Waardenburg Syndrome type 2 with no findings of mutations in the commonly associated genes.
February 15, 2018: Dermatology Online Journal
https://www.readbyqxmd.com/read/29621941/anti-melanogenic-effects-of-resorcinol-are-mediated-by-suppression-of-camp-signaling-and-activation-of-p38-mapk-signaling
#6
Mingyeong Kang, See-Hyoung Park, Sae Woong Oh, Seung Eun Lee, Ju Ah Yoo, Youn Hwa Nho, Sukyeon Lee, Byung Seok Han, Jae Youl Cho, Jongsung Lee
In this study, we investigated the inhibitory mechanisms of resorcinol in B16F10 mouse melanoma cells. We found that resorcinol reduced both the melanin content and tyrosinase activity in these cells. In addition, resorcinol suppressed the expression of melanogenic gene microphthalmia-associated transcriptional factor (MITF) and its downstream target genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. In addition, we found that resorcinol reduced intracellular cAMP levels and protein kinase A (PKA) activity, and increased phosphorylation of the p38 mitogen-activated protein kinase (MAPK)...
April 5, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29619268/enhancer-variants-reveal-a-conserved-transcription-factor-network-governed-by-pu-1-during-osteoclast-differentiation
#7
Heather A Carey, Blake E Hildreth, Jennifer A Geisler, Mara C Nickel, Jennifer Cabrera, Sankha Ghosh, Yue Jiang, Jing Yan, James Lee, Sandeep Makam, Nicholas A Young, Giancarlo R Valiente, Wael N Jarjour, Kun Huang, Thomas J Rosol, Ramiro E Toribio, Julia F Charles, Michael C Ostrowski, Sudarshana M Sharma
Genome-wide association studies (GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast- and osteoclast (OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor (TF) network was revealed...
2018: Bone Research
https://www.readbyqxmd.com/read/29614062/pseudotime-dynamics-in-melanoma-single-cell-transcriptomes-reveals-different-mechanisms-of-tumor-progression
#8
Henry Loeffler-Wirth, Hans Binder, Edith Willscher, Tobias Gerber, Manfred Kunz
Single-cell transcriptomics has been used for analysis of heterogeneous populations of cells during developmental processes and for analysis of tumor cell heterogeneity. More recently, analysis of pseudotime (PT) dynamics of heterogeneous cell populations has been established as a powerful concept to study developmental processes. Here we perform PT analysis of 3 melanoma short-term cultures with different genetic backgrounds to study specific and concordant properties of PT dynamics of selected cellular programs with impact on melanoma progression...
April 3, 2018: Biology
https://www.readbyqxmd.com/read/29614034/novel-1-e-3-e-5-e-1-6-bis-substituted-phenyl-hexa-1-3-5-triene-analogs-inhibit-melanogenesis-in-b16f10-cells-and-zebrafish
#9
Jisun Oh, Jungeun Kim, Jin Ho Jang, Sangwoo Lee, Chul Min Park, Woo-Keun Kim, Jong-Sang Kim
The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1 E ,3 E ,5 E )-1,6- bis (substituted phenyl)hexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively analyzed using three-dimensional quantitative structure-activity relationship approach. Inhibitory activities of these synthetic compounds against melanin synthesis were determined by evaluating melanin content and melanogenic regulatory enzyme expression in B16F10 cells...
April 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29574166/stem-cells-from-apical-papilla-promote-differentiation-of-human-pluripotent-stem-cells-towards-retinal-cells
#10
Fereshteh Karamali, Mohammad-Hossein Nasr Esfahani, Sara Taleahmad, Leila Satarian, Hossein Baharvand
Recently, we have found that human stem cells from apical papilla (SCAP) show a stromal cell-derived inducing activity (SDIA). To examine SDIA competence for retinal cells differentiation, we co-cultured SCAP with human pluripotent stem cells (hPSCs). In comparison with Matrigel-cultured hPSCs, SCAP significantly induces hPSCs to differentiate into rostral neural cells as demonstrated by upregulation of OTX2 and PAX6 and down-regulation of EN1, HOXB4 and HOXC8. Furthermore, the differentiated cells on SCAP significantly expressed eye-field markers, RAX, PAX6, LHX2 and SIX3 and showed five folds pigmented colonies...
March 2, 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29556371/%C3%AE-viniferin-improves-facial-hyperpigmentation-via-accelerating-feedback-termination-of-camp-pka-signaled-phosphorylation-circuit-in-facultative-melanogenesis
#11
Cheong-Yong Yun, Seon Mi Ko, Yong Pyo Choi, Beom Joon Kim, Jungno Lee, Jae Mun Kim, Ju Yeon Kim, Jin Yong Song, Song-Hee Kim, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Rationale: cAMP up-regulates microphthalmia-associated transcription factor subtype M (MITF-M) and tyrosinase (Tyro) in the generation of heavily pigmented melanosomes. Here, we communicate a therapeutic mechanism of hyperpigmented disorder by α-viniferin, an active constituent of Caragana sinica . Methods: We used cAMP-elevated melanocyte cultures or facial hyperpigmented patches for pigmentation assays, and applied immunoprecipitation, immunobloting, RT-PCR or reporter gene for elucidation of the antimelanogenic mechanism...
2018: Theranostics
https://www.readbyqxmd.com/read/29546053/-positive-regulation-of-rna-metabolic-process-ontology-group-highly-regulated-in-porcine-oocytes-matured-in-vitro-a-microarray-approach
#12
Piotr Celichowski, Mariusz J Nawrocki, Marta Dyszkiewicz-Konwińska, Maurycy Jankowski, Joanna Budna, Artur Bryja, Wiesława Kranc, Sylwia Borys, Sandra Knap, Sylwia Ciesiółka, Michal Jeseta, Karolina Piasecka-Stryczyńska, Ronza Khozmi, Dorota Bukowska, Paweł Antosik, Klaus P Brüssow, Małgorzata Bruska, Michał Nowicki, Maciej Zabel, Bartosz Kempisty
The cumulus-oocyte complexes (COCs) growth and development during folliculogenesis and oogenesis are accompanied by changes involving synthesis and accumulation of large amount of RNA and proteins. In this study, the transcriptomic profile of genes involved in "oocytes RNA synthesis" in relation to in vitro maturation in pigs was investigated for the first time. The RNA was isolated from oocytes before and after in vitro maturation (IVM). Interactions between differentially expressed genes/proteins belonging to "positive regulation of RNA metabolic process" ontology group were investigated by STRING10 software...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29545604/collagen-abundance-controls-melanoma-phenotypes-through-lineage-specific-microenvironment-sensing
#13
Zsofia Miskolczi, Michael P Smith, Emily J Rowling, Jennifer Ferguson, Jorge Barriuso, Claudia Wellbrock
Despite the general focus on an invasive and de-differentiated phenotype as main driver of cancer metastasis, in melanoma patients many metastatic lesions display a high degree of pigmentation, indicative for a differentiated phenotype. Indeed, studies in mice and fish show that melanoma cells switch to a differentiated phenotype at secondary sites, possibly because in melanoma differentiation is closely linked to proliferation through the lineage-specific transcriptional master regulator MITF. Importantly, while a lot of effort has gone into identifying factors that induce the de-differentiated/invasive phenotype, it is not well understood how the switch to the differentiated/proliferative phenotype is controlled...
March 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29531335/wnt-signaling-pathway-involvement-in-genotypic-and-phenotypic-variations-in-waardenburg-syndrome-type-2-with-mitf-mutations
#14
Xue-Ping Wang, Ya-Lan Liu, Ling-Yun Mei, Chu-Feng He, Zhi-Jie Niu, Jie Sun, Yu-Lin Zhao, Yong Feng, Hua Zhang
Mutation in the gene encoding microphthalmia-associated transcription factor (MITF) lead to Waardenburg syndrome 2 (WS2), an autosomal dominantly inherited syndrome with auditory-pigmentary abnormalities, which is clinically and genetically heterogeneous. Haploinsufficiency may be the underlying mechanism for WS2. However, the mechanisms explaining the genotypic and phenotypic variations in WS2 caused by MITF mutations are unclear. A previous study revealed that MITF interacts with LEF-1, an important factor in the Wnt signaling pathway, to regulate its own transcription through LEF-1-binding sites on the MITF promoter...
March 12, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29524259/immunohistochemical-identification-of-nail-matrix-melanocytes
#15
Gerzaín Rodríguez, Elga Johanna Vargas, María Claudia Abaúnza, Diana Marcela Díaz Quijano, Mario Melo-Uribe
BACKGROUND: No previous studies have been conducted to determine the normal number of nail matrix melanocytes in Latin American individuals. The objective of this work was to determine the number of melanocytes per linear millimeter present in the nail matrix and the nail bed in samples obtained from Colombian individuals. METHODS: Twenty-six unilateral biopsies were taken from 19 cadavers subjected to clinical and medico-legal autopsies. These biopsy samples were processed with conventional histotechnology and immunohistochemistry (IHC) with anti-HMB-45 and anti-MiTF...
March 10, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29522175/rare-variant-gene-based-association-study-of-hereditary-melanoma-using-whole-exome-sequencing
#16
Mykyta Artomov, Alexander J Stratigos, Ivana Kim, Raj Kumar, Martin Lauss, Bobby Y Reddy, Benchun Miao, Carla Daniela Robles-Espinoza, Aravind Sankar, Ching-Ni Njauw, Kristen Shannon, Evangelos S Gragoudas, Anne Marie Lane, Vivek Iyer, Julia A Newton-Bishop, D Timothy Bishop, Elizabeth A Holland, Graham J Mann, Tarjinder Singh, Mark J Daly, Hensin Tsao
Background: Extraordinary progress has been made in our understanding of common variants in many diseases, including melanoma. Because the contribution of rare coding variants is not as well characterized, we performed an exome-wide, gene-based association study of familial cutaneous melanoma (CM) and ocular melanoma (OM). Methods: Using 11 990 jointly processed individual DNA samples, whole-exome sequencing was performed, followed by large-scale joint variant calling using GATK (Genome Analysis ToolKit)...
December 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29518952/antimelanogenic-effect-of-an-oroxylum-indicum-seed-extract-by-suppression-of-mitf-expression-through-activation-of-mapk-signaling-protein
#17
Peijun Zhao, Md Badrul Alam, Hongyan An, Hee-Jeong Choi, Yeong Ho Cha, Chi-Yeol Yoo, Hyo-Hyun Kim, Sang-Han Lee
In this study, the antimelanogenic effect of an ethyl acetate fraction of Oroxylum indicum Vent. seeds (OISEA) and its underlying mechanisms in melan-a cells were investigated. Antimelanogenesis activity was confirmed by assessing inhibition of tyrosinase activity and melanin content in the cells. Both transcriptional and translational expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase related protein-1 and 2 (TYRP-1 and TYRP-2), were also examined. The results depicted that pretreatment of OISEA significantly inhibits not only tyrosinase activity, but melanin production and intracellular tyrosinase activity...
March 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29516164/cathepsin-k-expression-in-clear-cell-sugar-tumor-pecoma-of-the-lung
#18
Anna Caliò, Maria Cecilia Mengoli, Alberto Cavazza, Giulio Rossi, Claudio Ghimenton, Matteo Brunelli, Maurizio Pea, Marco Chilosi, Lisa Marcolini, Guido Martignoni
Clear cell "sugar" tumor is a rare benign neoplasm arising in the lung, considered as a part of the PEComa family. As PEComas of other sites, this tumor expresses melanocytic markers such as HMB45 and Melan-A. Despite cathepsin K, MITF and CD68 staining are known to be positive in a large number of PEComas and TFE3 rearrangement has been reported in a subset of PEComas, no data is available regarding the expression of these markers and the occurrence of TFE3 and TFEB rearrangement in clear cell "sugar" tumor of the lung...
March 7, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29512683/a-novel-psoralen-derivative-mpfc-enhances-melanogenesis-via-activation-of-p38-mapk-and-pka-signaling-pathways-in-b16-cells
#19
Li Yin, Guangxian Pang, Chao Niu, Maidina Habasi, Jun Dou, Haji Akber Aisa
As an active compound, psoralen is present in various Chinese herbal medicines and has exhibited significant activity in skin disease treatment. Its derivative 8-methoxypsoralan (8-MOP) is the most commonly used drug to induce repigmentation of vitiligo. In our previous screening assays, 4-methyl-6-phenyl-2H-furo[3,2-g]chromen-2-one (MPFC), a psoralen derivative, was identified as more effective tyrosinase and melanin activator than the positive control 8-MOP in consideration of low doses, as well as low toxicity...
June 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29510193/ccn1-cyr61-stimulates-melanogenesis-through-integrin-%C3%AE-6%C3%AE-1-p38-mapk-and-erk1-2-signaling-pathways-in-human-epidermal-melanocytes
#20
Zhongyi Xu, Li Chen, Min Jiang, Qianqian Wang, Chengfeng Zhang, Leihong Flora Xiang
Fibroblast-derived melanogenic paracrine mediators are known to play a role in melanogenesis. To investigate the effect of CCN1 (also called CYR61, cysteine-rich 61) on melanogenesis, normal human epidermal melanocytes (NHEMs) were treated with recombinant CCN1 protein. Our findings reveal that CCN1 activates melanogenesis through promoting melanosome maturation and upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1) and tyrosinase via integrin α6β1, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways...
March 3, 2018: Journal of Investigative Dermatology
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