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https://www.readbyqxmd.com/read/28319593/profiles-of-long-noncoding-rnas-in-hypertensive-rats-long-noncoding-rna-xr007793-regulates-cyclic-strain-induced-proliferation-and-migration-of-vascular-smooth-muscle-cells
#1
Qing-Ping Yao, Zhi-Wei Xie, Kai-Xuan Wang, Ping Zhang, Yue Han, Ying-Xin Qi, Zong-Lai Jiang
BACKGROUND: Long noncoding RNAs (lncRNAs) are being discovered in multiple diseases at a rapid pace. However, the contribution of lncRNAs to hypertension remains largely unknown. In hypertension, the vascular walls are exposed to abnormal mechanical cyclic strain, which leads to vascular remodelling. Here, we investigated the mechanobiological role of lncRNAs in hypertension. METHODS AND RESULTS: Differences in the lncRNAs and mRNAs between spontaneously hypertensive rats and Wistar-Kyoto rats were screened using a gene microarray...
March 17, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28303002/reciprocal-regulation-of-%C3%AE-globin-expression-by-exo-mirnas-relevance-to-%C3%AE-globin-silencing-in-%C3%AE-thalassemia-major
#2
Kuo-Ting Sun, Yu-Nan Huang, Kalaiselvi Palanisamy, Shih-Sheng Chang, I-Kuan Wang, Kang-Hsi Wu, Ping Chen, Ching-Tien Peng, Chi-Yuan Li
Induction of fetal hemoglobin (HbF) is a promising strategy in the treatment of β-thalassemia major (β-TM). The present study shows that plasma exosomal miRNAs (exo-miRs) are involved in γ-globin regulation. Exosomes shuttle miRNAs and mediate cell-cell communication. MiRNAs are regulators of biological processes through post-transcriptional targeting. Compared to HD (Healthy Donor), β-TM patients showed increased levels of plasma exosomes and the majority of exosomes had cellular origin from CD34+ cells...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28299656/roles-of-the-runx1-enhancer-in-normal-hematopoiesis-and-leukemogenesis
#3
Wei-Siang Liau, Phuong Cao Thi Ngoc, Takaomi Sanda
Enhancers are regulatory elements in genomic DNA that contain specific sequence motifs that are bound by DNA-binding transcription factors. The activity of enhancers is tightly regulated in an integrated and combinatorial manner, thus yielding complex patterns of transcription in different tissues. Identifying enhancers is crucial to understanding the physiological and pathogenic roles of their target genes. The RUNX1 intronic enhancer, eR1, acts in cis to regulate RUNX1 gene expression in hematopoietic stem cells (HSCs) and hemogenic endothelial cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28288039/lmo2-negative-expression-predicts-the-presence-of-myc-translocations-in-aggressive-b-cell-lymphomas
#4
Luis Colomo, Ivonne Vazquez, Natalia Papaleo, Blanca Espinet, Anna Ferrer, Catalina Franco, Laura Comerma, Silvia Hernandez, Xavier Calvo, Antonio Salar, Fina Climent, José Luis Mate, Pilar Forcada, Anna Mozos, Lara Nonell, Antonio Martinez, Anna Carrio, Dolors Costa, Ivan Dlouhy, Itziar Salaverria, Jose Ignacio Martin-Subero, Armando Lopez-Guillermo, Alexandra Valera, Elias Campo
MYC translocation is a defining feature of Burkitt lymphoma (BL), and the new category of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 translocations, and occurs in 6% to 15% of diffuse large B-cell lymphomas (DLBCLs). The low incidence of MYC translocations in DLBCL makes the genetic study of all these lymphomas cumbersome. Strategies based on an initial immunophenotypic screening to select cases with a high probability of carrying the translocation may be useful. LMO2 is a germinal center marker expressed in most lymphomas originated in these cells...
March 10, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28270453/activation-of-the-lmo2-oncogene-through-a-somatically-acquired-neomorphic-promoter-in-t-cell-acute-lymphoblastic-leukemia
#5
Sunniyat Rahman, Michael Magnussen, Theresa E León, Nadine Farah, Zhaodong Li, Brian J Abraham, Krisztina Z Alapi, Rachel J Mitchell, Tom Naughton, Adele K Fielding, Arnold Pizzey, Sophia Bustraan, Christopher Allen, Teodora Popa, Karin Pike-Overzet, Laura Garcia-Perez, Rosemary E Gale, David C Linch, Frank J T Staal, Richard A Young, A Thomas Look, Marc R Mansour
Somatic mutations within non-coding genomic regions that aberrantly activate oncogenes have remained poorly characterized. Here we describe recurrent activating intronic mutations of LMO2, a prominent oncogene in T-cell acute lymphoblastic leukemia (T-ALL). Heterozygous mutations were identified in PF-382 and DU.528 T-ALL cell lines, in addition to 3.7% (6/160) of pediatric and 5.5% (9/163) of adult T-ALL patient samples. The majority of indels harbour putative de novo MYB, ETS1 or RUNX1 consensus binding sites...
March 7, 2017: Blood
https://www.readbyqxmd.com/read/28181482/small-genomic-insertions-form-enhancers-that-misregulate-oncogenes
#6
Brian J Abraham, Denes Hnisz, Abraham S Weintraub, Nicholas Kwiatkowski, Charles H Li, Zhaodong Li, Nina Weichert-Leahey, Sunniyat Rahman, Yu Liu, Julia Etchin, Benshang Li, Shuhong Shen, Tong Ihn Lee, Jinghui Zhang, A Thomas Look, Marc R Mansour, Richard A Young
The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28179281/scl-tal1-a-multi-faceted-regulator-from-blood-development-to-disease
#7
Catherine Porcher, Hedia Chagraoui, Maiken S Kristiansen
SCL/TAL1 is an essential transcription factor in normal and malignant hematopoiesis. It is required for specification of the blood program during development, adult hematopoietic stem cell (HSC) survival and quiescence, and terminal maturation of select blood lineages. Following ectopic expression, SCL contributes to oncogenesis in T-cell acute lymphoblastic leukemia (T-ALL). Remarkably, SCL's activities are all mediated through nucleation of a core quaternary protein complex (SCL:E-protein:LMO2:LDB1) and dynamic recruitment of conserved combinatorial associations of additional regulators in a lineage- and stage-specific context...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28170369/lmo2-enhances-lamellipodia-filopodia-formation-in-basal-type-breast-cancer-cells-by-mediating-arp3-profilin1-interaction
#8
Ye Liu, Chao Wu, Tianhui Zhu, Wei Sun
BACKGROUND The human LMO2 gene was first cloned from an acute T lymphocytic leukemia patient; it is primarily expressed in hematopoietic and vascular endothelial systems, and functions as a pivotal transcriptional regulator during embryonic hematopoiesis and angiogenesis. However, some recent reports indicated that LMO2 is widely expressed in many tissues and tumors, predominantly in cytoplasm, and revealed complicated functions on tumor behaviors in a variety of cancer types. As an adaptor molecule, binding partners and function details of LMO2 in these solid tumors need to be further investigated...
February 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28123038/intron-1-gata-site-enhances-alas2-expression-indispensably-during-erythroid-differentiation
#9
Yingchi Zhang, Jingliao Zhang, Wenbin An, Yang Wan, Shihui Ma, Jie Yin, Xichuan Li, Jie Gao, Weiping Yuan, Ye Guo, James Douglas Engel, Lihong Shi, Tao Cheng, Xiaofan Zhu
The first intronic mutations in the intron 1 GATA site (int-1-GATA) of 5-aminolevulinate synthase 2 (ALAS2) have been identified in X-linked sideroblastic anemia (XLSA) pedigrees, strongly suggesting it could be causal mutations of XLSA. However, the function of this int-1-GATA site during in vivo development remains largely unknown. Here, we generated mice lacking a 13 bp fragment, including this int-1-GATA site (T AGATAA: AGCCCC) and found that hemizygous deletion led to an embryonic lethal phenotype due to severe anemia resulting from a lack of ALAS2 expression, indicating that this non-coding sequence is indispensable for ALAS2 expression in vivo Further analyses revealed that this int-1-GATA site anchored the GATA site in intron 8 (int-8-GATA) and the proximal promoter, forming a long-range loop to enhance ALAS2 expression by an enhancer complex including GATA1, TAL1, LMO2, LDB1 and Pol II at least, in erythroid cells...
January 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28069005/prognostic-efficacy-of-the-human-b-cell-lymphoma-prognostic-genes-in-predicting-disease-free-survival-dfs-in-the-canine-counterpart
#10
Mohamad Zamani-Ahmadmahmudi, Sina Aghasharif, Keyhan Ilbeigi
BACKGROUND: Canine B-cell lymphoma is deemed an ideal model of human non-Hodgkin's lymphoma where the lymphomas of both species share similar clinical features and biological behaviors. However there are some differences between tumor features in both species. In the current study, we sought to evaluate the prognostic efficacy of human B-cell lymphoma prognostic gene signatures in canine B-cell lymphoma. METHODS: The corresponding probe sets of 36 human B-cell lymphoma prognostic genes were retrieved from 2 canine B-cell lymphoma microarray datasets (GSE43664 and GSE39365) (76 samples), and prognostic probe sets were thereafter detected using the univariate and multivariate Cox proportional-hazard model and the Kaplan-Meier analysis...
January 9, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/27966264/pd1-and-pdl1-expression-in-primary-central-nervous-system-diffuse-large-b-cell-lymphoma-are-frequent-and-expression-of-pd1-predicts-poor-survival
#11
Marion Four, Valère Cacheux, Ariane Tempier, Dolorès Platero, Michel Fabbro, Grégory Marin, Nicolas Leventoux, Valérie Rigau, Valérie Costes-Martineau, Vanessa Szablewski
Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare and aggressive type of diffuse large B-cell lymphoma (DLBCL) whit poorly understood pathogenesis. Finding biomarkers associated with patient survival may be important for understanding its physiopathology and to develop new therapeutic approaches. We investigated 32 PCNS-DLBCL from immunocompetent patients for BCL2, CMYC, LMO2, and P53 expression and for cytogenetic aberrations of BCL2, BCL6, and MYC genes, all known for their prognostic value in systemic DLBCL (s-DLBCL)...
December 13, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27880729/lmo2-promotes-tumor-cell-invasion-and-metastasis-in-basal-type-breast-cancer-by-altering-actin-cytoskeleton-remodeling
#12
Ye Liu, Zhaoyang Wang, Di Huang, Chao Wu, Huihui Li, Xin Zhang, Bin Meng, Zongjin Li, Tianhui Zhu, Shuang Yang, Wei Sun
LMO2 is traditionally recognized as a pivotal transcriptional regulator during embryonic hematopoiesis and angionenesis, and its ectopic expression in T lymphocyte progenitors is closely correlated to the onset of acute T lymphocytic leukemia. However, recently studies revealed complicated expression features and dual functions of LMO2 on tumor behaviors in a variety of cancer types, including breast cancers. Basal-type breast cancer is one of the breast cancer subtypes and a prognostically unfavorable subtype among all breast cancers...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27869129/reprogramming-mouse-fibroblasts-into-engraftable-myeloerythroid-and-lymphoid-progenitors
#13
Hui Cheng, Heather Yin-Kuan Ang, Chadi A El Farran, Pin Li, Hai Tong Fang, Tong Ming Liu, Say Li Kong, Michael Lingzi Chin, Wei Yin Ling, Edwin Kok Hao Lim, Hu Li, Tara Huber, Kyle M Loh, Yuin-Han Loh, Bing Lim
Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase(+) megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27851970/the-hematopoietic-transcription-factors-runx1-and-erg-prevent-aml1-eto-oncogene-overexpression-and-onset-of-the-apoptosis-program-in-t-8-21-amls
#14
Amit Mandoli, Abhishek A Singh, Koen H M Prange, Esther Tijchon, Marjolein Oerlemans, Rene Dirks, Menno Ter Huurne, Albertus T J Wierenga, Eva M Janssen-Megens, Kim Berentsen, Nilofar Sharifi, Bowon Kim, Filomena Matarese, Luan N Nguyen, Nina C Hubner, Nagesha A Rao, Emile van den Akker, Lucia Altucci, Edo Vellenga, Hendrik G Stunnenberg, Joost H A Martens
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. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27825111/protocol-for-qrt-pcr-analysis-from-formalin-fixed-paraffin-embedded-tissue-sections-from-diffuse-large-b-cell-lymphoma-validation-of-the-six-gene-predictor-score
#15
Nilgun Tekin, Nader Omidvar, Tim Peter Morris, Paulette Conget, Flavia Bruna, Botond Timar, Eva Gagyi, Ranjan Basak, Omkar Naik, Chirayu Auewarakul, Narongrit Sritana, Debora Levy, Juliano Julio Cerci, Sergio Paulo Bydlowski, Juliana Pereira, Mark Pierre Dimamay, Filipinas Natividad, June-Key Chung, Nevin Belder, Isinsu Kuzu, Diana Paez, Maurizio Dondi, Robert Carr, Hilal Ozdag, Rose Ann Padua
As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27792641/lim-domain-only-2-regulates-endothelial-proliferation-angiogenesis-and-tissue-regeneration
#16
Shu Meng, Gianfranco Matrone, Jie Lv, Kaifu Chen, Wing Tak Wong, John P Cooke
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. LMO2 KD significantly impaired endothelial proliferation...
October 6, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27779255/lmo2-attenuates-tumor-growth-by-targeting-the-wnt-signaling-pathway-in-breast-and-colorectal-cancer
#17
Ye Liu, Di Huang, Zhaoyang Wang, Chao Wu, Zhao Zhang, Dan Wang, Zongjin Li, Tianhui Zhu, Shuang Yang, Wei Sun
The proto-oncogene LIM-domain only 2 (lmo2) was traditionally considered to be a pivotal transcriptional regulator in hematopoiesis and leukemia. Recently, the cytosolic localization of LMO2 was revealed in multiple epithelial tissues and a variety of solid tumors. However, the function of LMO2 in these epithelia and solid tumors remains largely unclear. The Wnt signaling pathway is a crucial determinant of development, and abnormalities in several key segments of this pathway contribute to oncogenesis. The current study demonstrated that LMO2 participates in the regulation of canonical Wnt signaling in the cytoplasm by binding to Dishevelled-1/2 (DVL-1/2) proteins...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27664237/superenhancer-reprogramming-drives-a-b-cell-epithelial-transition-and-high-risk-leukemia
#18
Yeguang Hu, Zhihong Zhang, Mariko Kashiwagi, Toshimi Yoshida, Ila Joshi, Nilamani Jena, Rajesh Somasundaram, Akinola Olumide Emmanuel, Mikael Sigvardsson, Julien Fitamant, Nabeel El-Bardeesy, Fotini Gounari, Richard A Van Etten, Katia Georgopoulos
IKAROS is required for the differentiation of highly proliferative pre-B-cell precursors, and loss of IKAROS function indicates poor prognosis in precursor B-cell acute lymphoblastic leukemia (B-ALL). Here we show that IKAROS regulates this developmental stage by positive and negative regulation of superenhancers with distinct lineage affiliations. IKAROS defines superenhancers at pre-B-cell differentiation genes together with B-cell master regulators such as PAX5, EBF1, and IRF4 but is required for a highly permissive chromatin environment, a function that cannot be compensated for by the other transcription factors...
September 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27579918/meta-analysis-of-transcriptome-regulation-during-induction-to-cardiac-myocyte-fate-from-mouse-and-human-fibroblasts
#19
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Moein Yaqubi, Abdulshakour Mohammadnia
Ectopic expression of a defined set of transcription factors (TFs) can directly convert fibroblasts into a cardiac myocyte cell fate. Beside inefficiency in generating induced cardiomyocytes (iCMs), the molecular mechanisms that regulate this process remained to be well defined. The main purpose of this study was to provide better insight on the transcriptome regulation and to introduce a new strategy for candidating TFs for the transdifferentiation process. Eight mouse and three human high quality microarray data sets were analyzed to find differentially expressed genes (DEGs), which we integrated with TF-binding sites and protein-protein interactions to construct gene regulatory and protein-protein interaction networks...
August 31, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27574108/foxp3-downregulation-in-nsclc-mediates-epithelial-mesenchymal-transition-via-nf-%C3%AE%C2%BAb-signaling
#20
Xi Wang, Ying Liu, Lingling Dai, Qi Liu, Liuqun Jia, Huan Wang, Lin An, Xiaogang Jing, Meng Liu, Pengfei Li, Zhe Cheng
Forkhead box P3 (Foxp3) is a member of forkhead box transcription factor family and it was identified as a tumor suppressor in various solid tumors. This study evaluated the expression of Foxp3 in non-small cell lung cancer (NSCLC) and investigated its role in epithelial‑mesenchymal transition (EMT) of cancer cells. qRT-PCR and western blot analysis were used for examining the expression of Foxp3 in NSCLC tissues and the non-tumor tissues. A tissue microarray was constructed and scored for evaluating the clinical significance of Foxp3 expression in NSCLC tissues...
October 2016: Oncology Reports
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