118 results match your criteria overexpression fli1


Bushen Yijing Decoction (BSYJ) exerts an anti-systemic sclerosis effect via regulating MicroRNA-26a /FLI1 axis.

Bioengineered 2021 Dec;12(1):1212-1225

Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Systemic sclerosis (SSc) refers to a group of autoimmune rheumatic diseases. Bushen Yijing decoction (BSYJ) is used for treating SSc. However, its underlying mechanism remains unknown. Read More

View Article and Full-Text PDF
December 2021

Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate.

Proc Natl Acad Sci U S A 2021 Feb;118(8)

Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065;

Cells derived from pluripotent sources in vitro must resemble those found in vivo as closely as possible at both transcriptional and functional levels in order to be a useful tool for studying diseases and developing therapeutics. Recently, differentiation of human pluripotent stem cells (hPSCs) into brain microvascular endothelial cells (ECs) with blood-brain barrier (BBB)-like properties has been reported. These cells have since been used as a robust in vitro BBB model for drug delivery and mechanistic understanding of neurological diseases. Read More

View Article and Full-Text PDF
February 2021

Genetically Engineered Mouse Model in Ewing Sarcoma.

Methods Mol Biol 2021 ;2226:183-189

Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.

Modeling Ewing sarcoma is challenging, since overexpression of EWS-FLI1 induces apoptosis and is not sufficient for tumor induction. It is therefore important to obtain the cell-of-origin of Ewing sarcoma that is tolerant of EWS-FLI1 expression. Here we describe the generation of the EWS-FLI1-expressing mouse model for Ewing sarcoma by selecting embryonic chondrogenic progenitor, eSZ cells that contain Ewing sarcoma precursors. Read More

View Article and Full-Text PDF

Ewing Sarcoma-Specific (Re)expression Models.

Methods Mol Biol 2021 ;2226:119-138

Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Gene expression and knockdown systems are powerful tools to study the function of single genes and their pathway interaction. Plasmid transfection and viral transduction have revolutionized the field of molecular biology and paved the ground for various gene-editing strategies such as TALEN, zinc finger nucleases, and ultimately CRISPR. In Ewing sarcoma (EwS), almost as many genes are repressed by the expression of EWSR1-FLI1 as are upregulated by the fusion oncogene. Read More

View Article and Full-Text PDF

Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type.

Cancers (Basel) 2020 Jul 15;12(7). Epub 2020 Jul 15.

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, Switzerland.

Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease that has been distinguished into at least two major molecular entities, the germinal center-like B cell (GCB) DLBCL and activated-like B cell (ABC) DLBCL, based on transcriptome expression profiling. A recurrent ch11q24.3 gain is observed in roughly a fourth of DLBCL cases resulting in the overexpression of two ETS transcription factor family members, ETS1 and FLI1. Read More

View Article and Full-Text PDF

TRIM3 Negatively Regulates Autophagy Through Promoting Degradation of Beclin1 in Ewing Sarcoma Cells.

Onco Targets Ther 2019 30;12:11587-11595. Epub 2019 Dec 30.

Department of Orthopedics, Qilu Hospital of Shandong University, Jinan 250012, Shandong, People's Republic of China.

Background And Aim: Ewing sarcoma (ES) is an aggressive neoplasm predominantly occurring in adolescents and has a poor prognosis when metastasized. In the current study, we were aiming to investigate the function of TRIM3 in autophagy in ES cells.

Methods: The expression of TRIM3 in Ewing sarcoma tissues and normal tissues was examined by quantitative PCR and western blot. Read More

View Article and Full-Text PDF
December 2019

FLI1 promotes protein translation via the transcriptional regulation of MKNK1 expression.

Int J Oncol 2020 Feb 16;56(2):430-438. Epub 2019 Dec 16.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Province Science City, High Tech Zone, Baiyun, Guiyang, Guizhou 550014, P.R. China.

The disruption of protein translation machinery is a common feature of cancer initiation and progression, and drugs that target protein translation offer new avenues for therapy. The translation initiation factor, eukaryotic initiation factor 4E (eIF4E), is induced in a number of cancer cell lines and is one such candidate for therapeutic intervention. Friend leukemia integration 1 (FLI1) is a potent oncogenic transcription factor that promotes various types of cancer by promoting several hallmarks of cancer progression. Read More

View Article and Full-Text PDF
February 2020

VEGF Promotes Endothelial Cell Differentiation from Human Embryonic Stem Cells Mainly Through PKC-ɛ/η Pathway.

Stem Cells Dev 2020 01 23;29(2):90-99. Epub 2019 Dec 23.

Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.

Human embryonic stem cells (hESCs) have unlimited proliferation capacity and can differentiate into most types of somatic cells. We previously described that the overexpression of FLI1 as well as the activation of protein kinase C (FLI1-PKC) could rapidly and efficiently differentiate hESCs into endothelial cells (ECs). However, the relationship between vascular endothelial growth factor (VEGF) and PKC in hESC-EC differentiation is debated, and the roles of different PKC isoforms in hESC-EC differentiation remain unknown. Read More

View Article and Full-Text PDF
January 2020

EWS-FLI1-mediated tenascin-C expression promotes tumour progression by targeting MALAT1 through integrin α5β1-mediated YAP activation in Ewing sarcoma.

Br J Cancer 2019 11 25;121(11):922-933. Epub 2019 Oct 25.

Spinal Tumor Center, Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, P. R. China.

Background: The extracellular matrix has been critically associated with the tumorigenesis and progression of Ewing sarcoma (ES). However, the regulatory and prognostic roles of tenascin-C (TNC) in ES remain unclear.

Methods: TNC expression was examined in specimens by immunohistochemistry, and the association of TNC expression with ES patient survival was also analysed. Read More

View Article and Full-Text PDF
November 2019

Fli-1 promotes proliferation and upregulates NANOGP8 expression in T-lymphocyte leukemia cells.

Biochimie 2020 Jan 15;168:1-9. Epub 2019 Oct 15.

Department of Biomedical Science, College of Life Science, CHA University, Seongnam-Si, Gyeonggi-Do, 13488, South Korea. Electronic address:

Friend leukemia integration 1 (Fli-1) is a member of the E26 transformation-specific (ETS) transcription factor family. Fli-1 regulates normal hematopoiesis and vasculogenesis, and its aberrant expression underlies virus-induced leukemias and various types of human cancers. NANOGP8, a retro-pseudogene of stem cell mediator NANOG, is expressed predominantly in cancer cells and plays a role in tumorigenesis. Read More

View Article and Full-Text PDF
January 2020

Identification of the intermediate filament protein synemin/SYNM as a target of myocardin family coactivators.

Am J Physiol Cell Physiol 2019 12 28;317(6):C1128-C1142. Epub 2019 Aug 28.

Department of Experimental Medical Science, Lund, Sweden.

Myocardin (MYOCD) is a critical regulator of smooth muscle cell (SMC) differentiation, but its transcriptional targets remain to be exhaustively characterized, especially at the protein level. Here we leveraged human RNA and protein expression data to identify novel potential MYOCD targets. Using correlation analyses we found several targets that we could confirm at the protein level, including SORBS1, SLMAP, SYNM, and MCAM. Read More

View Article and Full-Text PDF
December 2019

Downregulation of () follows the stepwise progression to gastric adenocarcinoma.

Oncotarget 2019 Jun 11;10(39):3852-3864. Epub 2019 Jun 11.

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.

Gastric adenocarcinoma (GC) is a leading cause of cancer-related deaths worldwide. The transcription factor gene () is methylated and downregulated in human GC tissues. Using human GC samples, we determined which cells downregulate , when downregulation occurs, if downregulation correlates with clinical-pathologic characteristics, and whether plays a role in invasion and/or proliferation of cultured cells. Read More

View Article and Full-Text PDF

Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma: the clinical significance of oncogenic EPS8.

J Hum Genet 2019 Jun 11;64(6):521-534. Epub 2019 Mar 11.

Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Our ongoing analyses identifying dysregulated microRNAs (miRNAs) and their controlled target RNAs have shed light on novel oncogenic pathways in pancreatic ductal adenocarcinoma (PDAC). The PDAC miRNA signature obtained by RNA sequencing showed that both strands of pre-miR-130b (miR-130b-5p, the passenger strand and miR-130b-3p, the guide strand) were significantly downregulated in cancer tissues. Our functional assays revealed that miR-130b-5p significantly blocked the malignant abilities of PDAC cell lines (PANC-1 and SW1990), e. Read More

View Article and Full-Text PDF

NKL homeobox gene NKX2-2 is aberrantly expressed in Hodgkin lymphoma.

Oncotarget 2018 Dec 25;9(101):37480-37496. Epub 2018 Dec 25.

Department of Human and Animal Cell Lines, Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.

NKL homeobox genes encode basic transcriptional regulators of cell and tissue differentiation. Recently, we described a hematopoietic NKL-code comprising nine specific NKL homeobox genes expressed in normal hematopoietic stem cells, lymphoid progenitors and during lymphopoiesis, highlighting their physiological role in the development of T-, B- and NK-cells. Here, we identified aberrant expression of the non-hematopoietic neural NKL homeobox gene NKX2-2 in about 12% of both, classical Hodgkin lymphoma (HL) and nodular lymphocyte predominant (NLP) HL patients. Read More

View Article and Full-Text PDF
December 2018

A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1.

Genome Biol 2018 12 11;19(1):218. Epub 2018 Dec 11.

Stem Cell and Cancer Center, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 133021, Jilin, China.

Background: Friend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. However, little is known about the mechanisms underlying the activation of this proto-oncogene in tumors.

Results: Immunohistochemical staining showed that FLI1 is aberrantly overexpressed in advanced stage and metastatic breast cancers. Read More

View Article and Full-Text PDF
December 2018

Transcription Factor Levels after Forward Programming of Human Pluripotent Stem Cells with GATA1, FLI1, and TAL1 Determine Megakaryocyte versus Erythroid Cell Fate Decision.

Stem Cell Reports 2018 12 29;11(6):1462-1478. Epub 2018 Nov 29.

Department of Haematology, University of Cambridge and NHS Blood and Transplant, Cambridge Blood Centre, Long Road, Cambridge CB2 0PT, UK; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, Cambridge CB2 1QR, UK. Electronic address:

The production of blood cells and their precursors from human pluripotent stem cells (hPSCs) in vitro has the potential to make a significant impact upon healthcare provision. We demonstrate that the forward programming of hPSCs through overexpression of GATA1, FLI1, and TAL1 leads to the production of a population of progenitors that can differentiate into megakaryocyte or erythroblasts. Using "rainbow" lentiviral vectors to quantify individual transgene expression in single cells, we demonstrate that the cell fate decision toward an erythroblast or megakaryocyte is dictated by the level of FLI1 expression and is independent of culture conditions. Read More

View Article and Full-Text PDF
December 2018

Expression of endothelin type B receptors (EDNRB) on smooth muscle cells is controlled by MKL2, ternary complex factors, and actin dynamics.

Am J Physiol Cell Physiol 2018 12 17;315(6):C873-C884. Epub 2018 Oct 17.

Department of Experimental Medical Science, Lund University , Lund , Sweden.

The endothelin type B receptor (ET or EDNRB) is highly plastic and is upregulated in smooth muscle cells (SMCs) by arterial injury and following organ culture in vitro. We hypothesized that this transcriptional plasticity may arise, in part, because EDNRB is controlled by a balance of transcriptional inputs from myocardin-related transcription factors (MRTFs) and ternary complex factors (TCFs). We found significant positive correlations between the TCFs ELK3 and FLI1 versus EDNRB in human arteries. Read More

View Article and Full-Text PDF
December 2018

phlda3 overexpression impairs specification of hemangioblasts and vascular development.

FEBS J 2018 11 20;285(21):4071-4081. Epub 2018 Sep 20.

Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China.

The phlda3 gene encodes a small, 127-amino acid protein with only a PH domain, and is involved in tumor suppression, proliferation of islet β-cells, insulin secretion, glucose tolerance, and liver injury. However, the role of phlda3 in vascular development is unknown. Here, we show that phlda3 overexpression decreases the expression levels of hemangioblast markers scl, fli1, and etsrp and intersegmental vessel (ISV) markers flk1 and cdh5, and disrupts ISV development in tg(flk1:GFP) and tg(fli1:GFP) zebrafish. Read More

View Article and Full-Text PDF
November 2018

Friend leukemia virus integration 1 is a predictor of poor prognosis of breast cancer and promotes metastasis and cancer stem cell properties of breast cancer cells.

Cancer Med 2018 08 4;7(8):3548-3560. Epub 2018 Jun 4.

Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China.

Breast cancer is the most common cancer in women worldwide; despite the developments in diagnosis and therapy, recurrence and metastasis remain the main causes of death among patients with breast cancer. This study aimed to identify a promising biomarker for this disease. The study clarified (1) the association between Friend leukemia virus integration 1 (FLI-1) and various molecular subtypes and (2) the prognostic value of FLI-1 in breast cancer. Read More

View Article and Full-Text PDF

FLI1 and PKC co-activation promote highly efficient differentiation of human embryonic stem cells into endothelial-like cells.

Cell Death Dis 2018 01 26;9(2):131. Epub 2018 Jan 26.

Institute of Reproduction & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.

Rationale-endothelial cells (ECs) play important roles in various regeneration processes and can be used in a variety of therapeutic applications, such as cardiac regeneration, gene therapy, tissue-engineered vascular grafts and prevascularized tissue transplants. ECs can be acquired from pluripotent and adult stem cells. To acquire ECs from human embryonic stem cells (hESCs) in a fast, efficient and economic manner. Read More

View Article and Full-Text PDF
January 2018

EWS-FLI1 positively regulates autophagy by increasing ATG4B expression in Ewing sarcoma cells.

Int J Mol Med 2017 Oct 29;40(4):1217-1225. Epub 2017 Aug 29.

Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

Ewing sarcoma (ES) is the most common malignant bone tumor in children and young adults. It is characterized by chromosomal translocations fusing the EWS gene with an ETS oncogene, most frequently FLI1. In the present study, the authors aimed to investigate the function of EWS-FLI1 in autophagy in ES cells, and identified that EWS-FLI1 positively regulates autophagy in ES cells. Read More

View Article and Full-Text PDF
October 2017

Lmo2 (LIM-Domain-Only 2) Modulates Sphk1 (Sphingosine Kinase) and Promotes Endothelial Cell Migration.

Arterioscler Thromb Vasc Biol 2017 10 3;37(10):1860-1868. Epub 2017 Aug 3.

From the Department of Cardiovascular Sciences, Houston Methodist Research Institute, TX.

Objective: (LIM-domain-only)2 transcription factor is involved in hematopoiesis and vascular remodeling. (sphingosine kinase)1 phosphorylates sphingosine to S1P (sphingosine-1-phosphate). We hypothesized that regulates to promote endothelial cell (EC) migration and vascular development. Read More

View Article and Full-Text PDF
October 2017

Gastroblastoma harbors a recurrent somatic MALAT1-GLI1 fusion gene.

Mod Pathol 2017 10 21;30(10):1443-1452. Epub 2017 Jul 21.

Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Gastroblastoma is a rare distinctive biphasic tumor of the stomach. The molecular biology of gastroblastoma has not been studied, and no affirmative diagnostic markers have been developed. We retrieved two gastroblastomas from the consultation practices of the authors and performed transcriptome sequencing on formalin-fixed paraffin-embedded tissue. Read More

View Article and Full-Text PDF
October 2017

Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect.

Int J Oncol 2017 Aug 2;51(2):456-466. Epub 2017 Jun 2.

The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, Guizhou 550014, P.R. China.

The ETS transcription factors play a critical role during hematopoiesis. In F-MuLV-induced erythroleukemia, Fli‑1 insertional activation producing high expression of this transcription factor required to promote proliferation. How deregulated Fli‑1 expression alters the balance between erythroid differentiation and proliferation is unknown. Read More

View Article and Full-Text PDF

MiR-193b, downregulated in Ewing Sarcoma, targets the ErbB4 oncogene to inhibit anchorage-independent growth.

PLoS One 2017 18;12(5):e0178028. Epub 2017 May 18.

Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, United States of America.

Ewing Sarcoma is an aggressive, oncofusion-driven, malignant neoplasm of bone and soft tissue affecting predominantly children and young adults. Seeking to identify potential novel therapeutic targets/agents for this disease, our previous studies uncovered microRNAs regulated by EWS/Fli1, the most common oncofusion, with growth modulatory properties. In the present study, we sought to identify EWS/Fli1-repressed, growth suppressive, microRNAs potentially amenable to replacement in Ewing Sarcoma cells. Read More

View Article and Full-Text PDF
September 2017

FLI1 level during megakaryopoiesis affects thrombopoiesis and platelet biology.

Blood 2017 06 21;129(26):3486-3494. Epub 2017 Apr 21.

Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Friend leukemia virus integration 1 (FLI1), a critical transcription factor (TF) during megakaryocyte differentiation, is among genes hemizygously deleted in Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau syndrome (PTSx). Recently, heterozygote human mutations have been ascribed to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand these clinical disorders, beginning with iPSCs generated from a patient with PTSx and iPSCs from a control line with a targeted heterozygous knockout (FLI1). Read More

View Article and Full-Text PDF

C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells.

Oncotarget 2017 Apr;8(16):26013-26026

Department of Pediatrics, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Read More

View Article and Full-Text PDF

MicroRNA-22 regulates inflammation and angiogenesis via targeting VE-cadherin.

FEBS Lett 2017 02 6;591(3):513-526. Epub 2017 Feb 6.

Department of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.

The vascular endothelial (VE)-cadherin functions as an endothelial barrier protein controlling endothelial permeability and leukocyte transmigration. Developmental studies indicate that VE-cadherin also plays a vital role in angiogenesis. MicroRNA-22 plays important roles in cardiovascular diseases including cardiac hypertrophy and heart failure. Read More

View Article and Full-Text PDF
February 2017

The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs.

Cell Rep 2016 11;17(8):2087-2100

Radboud University, Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, 6500 HB Nijmegen, the Netherlands; Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Vico Luigi de Crecchio 7, 80138 Napoli, Italy. Electronic address:

The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. Read More

View Article and Full-Text PDF
November 2016

LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration.

J Am Heart Assoc 2016 10 6;5(10). Epub 2016 Oct 6.

Center for Cardiovascular Regeneration, Houston Methodist Research Institute, Houston, TX

Background: LIM domain only 2 (LMO2, human gene) is a key transcription factor that regulates hematopoiesis and vascular development. However, its role in adult endothelial function has been incompletely characterized.

Methods And Results: In vitro loss- and gain-of-function studies on LMO2 were performed in human umbilical vein endothelial cells with lentiviral overexpression or short hairpin RNA knockdown (KD) of LMO2, respectively. Read More

View Article and Full-Text PDF
October 2016