keyword
https://read.qxmd.com/read/36969082/lsd1-inhibition-modulates-transcription-factor-networks-in-myeloid-malignancies
#21
REVIEW
Emily E Hartung, Kanwaldeep Singh, Tobias Berg
Acute Myeloid Leukemia (AML) is a type of cancer of the blood system that is characterized by an accumulation of immature hematopoietic cells in the bone marrow and blood. Its pathogenesis is characterized by an increase in self-renewal and block in differentiation in hematopoietic stem and progenitor cells. Underlying its pathogenesis is the acquisition of mutations in these cells. As there are many different mutations found in AML that can occur in different combinations the disease is very heterogeneous...
2023: Frontiers in Oncology
https://read.qxmd.com/read/36936167/a-large-scale-screening-and-functional-sorting-of-tumour-microenvironment-prognostic-genes-for-breast-cancer-patients
#22
JOURNAL ARTICLE
Bo Xiao, Mingwei Li, Mingxuan Cui, Chengliang Yin, Bo Zhang
PURPOSE: The aim of this study was to systematically establish a comprehensive tumour microenvironment (TME)-relevant prognostic gene and target miRNA network for breast cancer patients. METHODS: Based on a large-scale screening of TME-relevant prognostic genes (760 genes) for breast cancer patients, the prognostic model was established. The primary TME prognostic genes were selected from the constructing database and verified in the testing database. The internal relationships between the potential TME prognostic genes and the prognosis of breast cancer patients were explored in depth...
2023: Frontiers in Endocrinology
https://read.qxmd.com/read/36913305/c-ebp%C3%AE-cooperates-with-myb-to-maintain-the-oncogenic-program-of-aml-cells
#23
EDITORIAL
Karl-Heinz Klempnauer
Studies on the role of transcription factor MYB in acute myeloid leukemia (AML) have identified MYB as a key regulator of a transcriptional program for self-renewal of AML cells. Recent work summarized here has now highlighted the CCAAT-box/enhancer binding protein beta (C/EBPβ) as an essential factor and potential therapeutic target that cooperates with MYB and coactivator p300 in the maintenance of the leukemic cells.
March 11, 2023: Oncotarget
https://read.qxmd.com/read/36905855/generation-of-p27icreer-transgenic-mice-a-tool-for-inducible-gene-expression-in-supporting-cells-in-the-cochlea
#24
JOURNAL ARTICLE
Yuyan Gu, Yikang Huang, Gaogan Jia, Yanping Zhang, Yan Chen, Wenyan Li
The loss of cochlear hair cells (HCs) is an important cause of sensorineural hearing loss, and finding ways to regenerate HCs would be the ideal way forward for restoring hearing. In this research field, tamoxifen-inducible Cre recombinase (iCreER) transgenic mice and the Cre-loxp system are widely used to manipulate gene expression in supporting cells (SCs), which lie beneath the sensory HCs and are a natural source for HC regeneration. However, many iCreER transgenic lines are of limited utility because they cannot target all subtypes of SCs or they cannot be used in the adult stage...
March 4, 2023: Hearing Research
https://read.qxmd.com/read/36862552/the-early-neutrophil-committed-progenitors-aberrantly-differentiate-into-immunoregulatory-monocytes-during-emergency-myelopoiesis
#25
JOURNAL ARTICLE
Naoki Ikeda, Hiroaki Kubota, Risa Suzuki, Mitsuki Morita, Ayana Yoshimura, Yuya Osada, Keigo Kishida, Daiki Kitamura, Ayaka Iwata, Satoshi Yotsumoto, Daisuke Kurotaki, Koutarou Nishimura, Akira Nishiyama, Tomohiko Tamura, Takashi Kamatani, Tatsuhiko Tsunoda, Miyako Murakawa, Yasuhiro Asahina, Yoshihiro Hayashi, Hironori Harada, Yuka Harada, Asumi Yokota, Hideyo Hirai, Takao Seki, Makoto Kuwahara, Masakatsu Yamashita, Shigeyuki Shichino, Masato Tanaka, Kenichi Asano
Inflammatory stimuli cause a state of emergency myelopoiesis leading to neutrophil-like monocyte expansion. However, their function, the committed precursors, or growth factors remain elusive. In this study we find that Ym1+ Ly6Chi monocytes, an immunoregulatory entity of neutrophil-like monocytes, arise from progenitors of neutrophil 1 (proNeu1). Granulocyte-colony stimulating factor (G-CSF) favors the production of neutrophil-like monocytes through previously unknown CD81+ CX3CR1lo monocyte precursors. GFI1 promotes the differentiation of proNeu2 from proNeu1 at the cost of producing neutrophil-like monocytes...
February 28, 2023: Cell Reports
https://read.qxmd.com/read/36758788/long-term-exposure-of-cigarette-smoke-condensate-csc-mediates-transcriptomic-changes-in-normal-human-lung-epithelial-beas-2b-cells-and-protection-by-garlic-compounds
#26
JOURNAL ARTICLE
Rasika R Hudlikar, Pochung Jordan Chou, Hsiao-Chen Dina Kuo, Davit Sargsyan, Renyi Wu, Ah-Ng Kong
Chronic cigarette smoke condensate (CSC) exposure is one of the preventable risk factors in the CS-induced lung cancer. However, understanding the mechanism of cellular transformation induced by CS in the lung remains limited. We investigated the effect of long term exposure of CSC in human normal lung epithelial Beas-2b cells, and chemopreventive mechanism of organosulphur garlic compounds, diallyl sulphide (DAS) and diallyl disulphide (DADS) using Next Generation Sequencing (NGS) transcriptomic analysis. CSC regulated 1077 genes and of these 36 genes are modulated by DAS while 101 genes by DADS...
February 7, 2023: Food and Chemical Toxicology
https://read.qxmd.com/read/36672361/serum-mass-spectrometry-proteomics-and-protein-set-identification-in-response-to-folfox-4-in-drug-resistant-ovarian-carcinoma
#27
JOURNAL ARTICLE
Domenico D'Arca, Leda Severi, Stefania Ferrari, Luca Dozza, Gaetano Marverti, Fulvio Magni, Clizia Chinello, Lisa Pagani, Lorenzo Tagliazucchi, Marco Villani, Gianluca d'Addese, Isabella Piga, Vincenza Conteduca, Lorena Rossi, Giorgia Gurioli, Ugo De Giorgi, Lorena Losi, Maria Paola Costi
Ovarian cancer is a highly lethal gynecological malignancy. Drug resistance rapidly occurs, and different therapeutic approaches are needed. So far, no biomarkers have been discovered to predict early response to therapies in the case of multi-treated ovarian cancer patients. The aim of our investigation was to identify a protein panel and the molecular pathways involved in chemotherapy response through a combination of studying proteomics and network enrichment analysis by considering a subset of samples from a clinical setting...
January 8, 2023: Cancers
https://read.qxmd.com/read/36623910/retraction-notice-to-mir-650-regulates-the-proliferation-migration-and-invasion-of-human-oral-cancer-by-targeting-growth-factor-independent-1-gfi1-biochimie-156-2018-69-78
#28
Sun Ningning, Sun Libo, Wu Chuanbin, Sun Haijiang, Zhou Qing
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Following concerns raised by Dr. E. Bik and an anonymous reader, the journal conducted an investigation and found evidence that there had been improper manipulation and duplication of images in Figs...
January 2023: Biochimie
https://read.qxmd.com/read/36594016/the-scaffolding-function-of-lsd1-kdm1a-reinforces-a-negative-feedback-loop-to-repress-stem-cell-gene-expression-during-primitive-hematopoiesis
#29
JOURNAL ARTICLE
Mattie J Casey, Alexandra M Call, Annika V Thorpe, Cicely A Jette, Michael E Engel, Rodney A Stewart
Lsd1/Kdm1a functions both as a histone demethylase enzyme and as a scaffold for assembling chromatin modifier and transcription factor complexes to regulate gene expression. The relative contributions of Lsd1's demethylase and scaffolding functions during embryogenesis are not known. Here, we analyze two independent zebrafish lsd1/kdm1a mutant lines and show Lsd1 is required to repress primitive hematopoietic stem cell gene expression. Lsd1 rescue constructs containing point mutations that selectively abrogate its demethylase or scaffolding capacity demonstrate the scaffolding function of Lsd1, not its demethylase activity, is required for repression of gene expression in vivo ...
January 20, 2023: IScience
https://read.qxmd.com/read/36532072/fcgr2c-an-emerging-immune-gene-for-predicting-sepsis-outcome
#30
JOURNAL ARTICLE
Si Liu, Yao Lu Zhang, Lu Yao Zhang, Guang Ju Zhao, Zhong Qiu Lu
BACKGROUND: Sepsis is a life-threatening disease associated with immunosuppression. Immunosuppression could ultimately increase sepsis mortality. This study aimed to identify the prognostic biomarkers related to immunity in sepsis. METHODS: Public datasets of sepsis downloaded from the Gene Expression Omnibus (GEO) database were divided into the discovery cohort and the first validation cohort. We used R software to screen differentially expressed genes (DEGs) and analyzed DEGs' functional enrichment in the discovery dataset...
2022: Frontiers in Immunology
https://read.qxmd.com/read/36445327/cellular-reprogramming-with-atoh1-gfi1-and-pou4f3-implicate-epigenetic-changes-and-cell-cell-signaling-as-obstacles-to-hair-cell-regeneration-in-mature-mammals
#31
JOURNAL ARTICLE
Amrita A Iyer, Ishwar Hosamani, John D Nguyen, Tiantian Cai, Sunita Singh, Melissa M McGovern, Lisa Beyer, Hongyuan Zhang, Hsin-I Jen, Rizwan Yousaf, Onur Birol, Jenny J Sun, Russell S Ray, Yehoash Raphael, Neil Segil, Andrew K Groves
Reprogramming of the cochlea with hair-cell-specific transcription factors such as ATOH1 has been proposed as a potential therapeutic strategy for hearing loss. ATOH1 expression in the developing cochlea can efficiently induce hair cell regeneration but the efficiency of hair cell reprogramming declines rapidly as the cochlea matures. We developed Cre-inducible mice to compare hair cell reprogramming with ATOH1 alone or in combination with two other hair cell transcription factors, GFI1 and POU4F3. In newborn mice, all transcription factor combinations tested produced large numbers of cells with the morphology of hair cells and rudimentary mechanotransduction properties...
November 29, 2022: ELife
https://read.qxmd.com/read/36420143/repurposing-the-lineage-determining-transcription-factor-atoh1-without-redistributing-its-genomic-binding-sites
#32
JOURNAL ARTICLE
Aida Costa, Lynn M Powell, Mattias Malaguti, Abdenour Soufi, Sally Lowell, Andrew P Jarman
Although the lineage-determining ability of transcription factors is often modulated according to cellular context, the mechanisms by which such switching occurs are not well known. Using a transcriptional programming model, we found that Atoh1 is repurposed from a neuronal to an inner ear hair cell (HC) determinant by the combined activities of Gfi1 and Pou4f3. In this process, Atoh1 maintains its regulation of neuronal genes but gains ability to regulate HC genes. Pou4f3 enables Atoh1 access to genomic locations controlling the expression of sensory (including HC) genes, but Atoh1 + Pou4f3 are not sufficient for HC differentiation...
2022: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/36304450/central-gene-transcriptional-regulatory-networks-shaping-monocyte-development-in-bone-marrow
#33
JOURNAL ARTICLE
Zhaoqi Zhang, Elhusseny A Bossila, Ling Li, Songnian Hu, Yong Zhao
The development of monocytes in bone marrow is a complex process with multiple steps. We used RNA-seq data to analyze the transcriptome profiles in developing stages of monocytes, including hematopoietic stem cells (HSCs), common myeloid progenitors (CMPs), granulocyte-monocyte progenitors (GMPs), and monocytes. We found that genes related to potassium and other cation transmembrane activities and ion binding were upregulated during the differentiation of HSCs into CMPs. Protein transport and membrane surface functional molecules were significantly upregulated in the GMP stage...
2022: Frontiers in Immunology
https://read.qxmd.com/read/36264868/identification-of-mirna-mrna-tfs-regulatory-network-and-crucial-pathways-involved-in-asthma-through-advanced-systems-biology-approaches
#34
JOURNAL ARTICLE
Noor Ahmad Shaik, Khalidah Nasser, Arif Mohammed, Abdulrahman Mujalli, Ahmad A Obaid, Ashraf A El-Harouni, Ramu Elango, Babajan Banaganapalli
Asthma is a life-threatening and chronic inflammatory lung disease that is posing a true global health challenge. The genetic basis of the disease is fairly well examined. However, the molecular crosstalk between microRNAs (miRNAs), target genes, and transcription factors (TFs) networks and their contribution to disease pathogenesis and progression is not well explored. Therefore, this study was aimed at dissecting the molecular network between mRNAs, miRNAs, and TFs using robust computational biology approaches...
2022: PloS One
https://read.qxmd.com/read/36188575/constructing-a-molecular-subtype-model-of-colon-cancer-using-machine-learning
#35
JOURNAL ARTICLE
Bo Zhou, Jiazi Yu, Xingchen Cai, Shugeng Wu
Background: Colon cancer (CRC) is one of the malignant tumors with a high incidence in the world. Many previous studies on CRC have focused on clinical research. With the in-depth study of CRC, the role of molecular mechanisms in CRC has become increasingly important. Currently, machine learning is widely used in medicine. By combining machine learning with molecular mechanisms, we can better understand CRC's pathogenesis and develop new treatments for it. Methods and materials: We used the R language to construct molecular subtypes of colon cancer and subsequently explored prognostic genes with GEPIA2...
2022: Frontiers in Pharmacology
https://read.qxmd.com/read/36171271/hmg20b-stabilizes-association-of-lsd1-with-gfi1-on-chromatin-to-confer-transcription-repression-and-leukemia-cell-differentiation-block
#36
JOURNAL ARTICLE
Alba Maiques-Diaz, Luciano Nicosia, Naseer J Basma, Isabel Romero-Camarero, Francesco Camera, Gary J Spencer, Fabio M R Amaral, Fabrizio Simeoni, Bettina Wingelhofer, Andrew J K Williamson, Andrew Pierce, Anthony D Whetton, Tim C P Somervaille
Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. To explore the wider consequences of LSD1 inhibition on the LSD1 protein complex we applied mass spectrometry technologies...
September 28, 2022: Oncogene
https://read.qxmd.com/read/36165199/cutting-edge-the-expression-of-transcription-inhibitor-gfi1-is-induced-by-retinoic-acid-to-rein-in-th9-polarization
#37
JOURNAL ARTICLE
Leon Friesen, Raymond Kostlan, Qingyang Liu, Hao Yu, Jinfang Zhu, Nicholas Lukacs, Chang H Kim
IL-9, produced mainly by specialized T cells, mast cells, and group 2 innate lymphoid cells, regulates immune responses, including anti-helminth and allergic responses. Polarization of naive CD4 T cells into IL-9-producing T cells (Th9s) is induced by IL-4 and TGF-β1 or IL-1β. In this article, we report that the transcription factor growth factor-independent 1 transcriptional repressor (GFI1) plays a negative role in mouse Th9 polarization. Moreover, the expression of GFI1 is controlled by liganded RARα, allowing GFI1 to mediate the negative effect of retinoic acid on IL-9 expression...
October 1, 2022: Journal of Immunology
https://read.qxmd.com/read/36071278/author-correction-gfi1-tethers-the-nurd-complex-to-open-and-transcriptionally-active-chromatin-in-myeloid-progenitors
#38
Anne Helness, Jennifer Fraszczak, Charles Joly-Beauparlant, Halil Bagci, Christian Trahan, Kaifee Arman, Peiman Shooshtarizadeh, Riyan Chen, Marina Ayoub, Jean-François Côté, Marlene Oeffinger, Arnaud Droit, Tarik Möröy
No abstract text is available yet for this article.
September 7, 2022: Communications Biology
https://read.qxmd.com/read/36003783/presence-of-the-gfi1-36n-single-nucleotide-polymorphism-enhances-the-response-of-mll-af9-leukemic-cells-to-cdk4-6-inhibition
#39
JOURNAL ARTICLE
Jan Vorwerk, Kaiyan Sun, Daria Frank, Felix Neumann, Jana Hüve, Paulina Marie Budde, Longlong Liu, Xiaoqing Xie, Pradeep Kumar Patnana, Helal Mohammed Mohammed Ahmed, Bertram Opalka, Georg Lenz, Ashok Kumar Jayavelu, Cyrus Khandanpour
The zinc finger protein Growth Factor Independence 1 (GFI1) acts as a transcriptional repressor regulating differentiation of myeloid and lymphoid cells. A single nucleotide polymorphism of GFI1 , GFI1-36N , has a prevalence of 7% in healthy Caucasians and 15% in acute myeloid leukemia (AML) patients, hence most probably predisposing to AML. One reason for this is that GFI1-36N differs from the wildtype form GFI1-36S regarding its ability to induce epigenetic changes resulting in a derepression of oncogenes...
2022: Frontiers in Oncology
https://read.qxmd.com/read/35819844/hematopoietic-transcription-factor-gfi1-promotes-anchorage-independence-by-sustaining-erk-activity-in-cancer-cells
#40
JOURNAL ARTICLE
Hao Wang, Zhenzhen Lin, Zhe Nian, Wei Zhang, Wenxu Liu, Fei Yan, Zengtuan Xiao, Xia Wang, Zhenfa Zhang, Zhenyi Ma, Zhe Liu
The switch from anchorage-dependent to anchorage-independent growth is essential for epithelial metastasis. The underlying mechanism, however, is not fully understood. In this study, we identified growth factor independent-1 (GFI1), a transcription factor that drives the transition from adherent endothelial cells to suspended hematopoietic cells during hematopoiesis, as a critical regulator of anchorage independence in lung cancer cells. GFI1 elevated the numbers of circulating and lung-infiltrating tumor cells in xenograft models and predicted poor prognosis of patients with lung cancer...
September 1, 2022: Journal of Clinical Investigation
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