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Lin Fu, Jinlong Shi, Anqi Liu, Lei Zhou, Mengmeng Jiang, Huaping Fu, Keman Xu, Dandan Li, Ailing Deng, Qingyi Zhang, Yifan Pang, Yujie Guo, Kai Hu, Jiansuo Zhou, Yapeng Wang, Wenrong Huang, Yu Jing, Liping Dou, Lili Wang, Kailin Xu, Xiaoyan Ke, Clara Nervi, Yonghui Li, Li Yu
MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 down-regulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
Zheng Fang, Jingxu Shao, Qingbei Weng
Cells of the P8-Se301-C1 strain are Spodoptera exigua cell clones that each harbor a partial version of the S. exigua multiple nucleopolyhedrovirus (SeMNPV) genome and which are resistant to homologous SeMNPV infections. The cells produce no viral progeny, suggesting that the infection is a latent-like viral infection. To investigate the SeMNPV genes harbored in the P8-Se301-C1 cells, the de novo transcriptomes of P8-Se301-C1 cells and S. exigua Se301 cells were analyzed and compared. A total of 54,569,296 reads were obtained from the P8-Se301-C1 cells that yielded 112,565 final unigenes with a mean length of 1,093 nt...
October 18, 2016: Virologica Sinica
Sonia Carturan, Jessica Petiti, Valentina Rosso, Chiara Calabrese, Elisabetta Signorino, Giada Bot-Sartor, Paolo Nicoli, Daniela Gallo, Enrico Bracco, Alessandro Morotti, Cristina Panuzzo, Enrico Gottardi, Francesco Frassoni, Giuseppe Saglio, Daniela Cilloni
Meningioma 1 (MN1) gene overexpression has been reported in acute myeloid leukaemia (AML) patients and identified as a negative prognostic factor. In order to characterize patients presenting gene overexpression and to verify if MN1 transcript could be a useful marker for minimal residual disease detection, MN1 was quantified in 136 AML patients with different cytogenetic risk and in 50 normal controls. In 20 patients bearing a fusion gene transcript suitable for minimal residual disease quantitative assessment and in 8 patients with NPM1 mutation, we performed a simultaneous analysis of MN1 and the fusion-gene transcript or NPM1 mutation during follow-up...
September 27, 2016: Oncotarget
Jaime I Davila, Numrah M Fadra, Xiaoke Wang, Amber M McDonald, Asha A Nair, Barbara R Crusan, Xianglin Wu, Joseph H Blommel, Jin Jen, Kandelaria M Rumilla, Robert B Jenkins, Umut Aypar, Eric W Klee, Benjamin R Kipp, Kevin C Halling
BACKGROUND: RNA-seq is a well-established method for studying the transcriptome. Popular methods for library preparation in RNA-seq such as Illumina TruSeq® RNA v2 kit use a poly-A pulldown strategy. Such methods can cause loss of coverage at the 5' end of genes, impacting the ability to detect fusions when used on degraded samples. The goal of this study was to quantify the effects RNA degradation has on fusion detection when using poly-A selected mRNA and to identify the variables involved in this process...
October 20, 2016: BMC Genomics
Sapna M Amin, Adam Beattie, Xia Ling, Lawrence J Jennings, Joan Guitart
Mammary analog secretory carcinoma (MASC) is a recently described tumor of the salivary glands named for its morphological and molecular similarity to secretory carcinoma of the breast. Many primary carcinomas arising from the adnexal glands also share similar morphology to those arising from the breast. Brandt et al first described primary cutaneous MASC in 2009 and since then only 2 other cases have been reported. Herein, we describe a long-standing mass on the arm of an otherwise healthy 40-year-old female...
November 2016: American Journal of Dermatopathology
Dekai Wang, Heqin Liu, Guowei Zhai, Liangsheng Wang, Jianfeng Shao, Yuezhi Tao
Functional chloroplast generation depends on the precise coordination of gene expression between the plastid and the nucleus and is essential for plant growth and development. In this study, a rice (Oryza sativa) mutant that exhibited albino and seedling-lethal phenotypes was isolated from a(60)Co-irradiated rice population. The mutant gene was identified as an ortholog of the Arabidopsis plastid transcriptionally active chromosome protein 2 (pTAC2) gene, and the mutant strain was designated osptac2. Sequence and transcription analyses showed that OspTAC2 encodes a putative chloroplast protein consisting of 10 pentratricopeptide repeat (PPR) domains and a C-terminal small MutS-related (SMR) domain...
September 15, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Tao He, Didier Surdez, Juha K Rantala, Saija Haapa-Paananen, Jozef Ban, Maximilian Kauer, Eleni Tomazou, Vidal Fey, Javier Alonso, Heinrich Kovar, Olivier Delattre, Kristiina Iljin
A translocation leading to the formation of an oncogenic EWS-ETS fusion protein defines Ewing sarcoma. The most frequent gene fusion, present in 85 percent of Ewing sarcomas, is EWS-FLI1. Here, a high-throughput RNA interference screen was performed to identify genes whose function is critical for EWS-FLI1 driven cell viability. In total, 6781 genes were targeted by siRNA molecules and the screen was performed both in presence and absence of doxycycline-inducible expression of the EWS-FLI1 shRNA in A673/TR/shEF Ewing sarcoma cells...
October 16, 2016: Gene
Maria Böhm, Marco Wachtel, Joana G Marques, Natalie Streiff, Dominik Laubscher, Paolo Nanni, Kamel Mamchaoui, Raffaella Santoro, Beat W Schäfer
A vast number of cancer genes are transcription factors that drive tumorigenesis as oncogenic fusion proteins. Although the direct targeting of transcription factors remains challenging, therapies aimed at oncogenic fusion proteins are attractive as potential treatments for cancer. There is particular interest in targeting the oncogenic PAX3-FOXO1 fusion transcription factor, which induces alveolar rhabdomyosarcoma (aRMS), an aggressive cancer of skeletal muscle cells for which patient outcomes remain dismal...
October 17, 2016: Journal of Clinical Investigation
Jesus Duque-Afonso, Chiou-Hong Lin, Kyuho Han, Michael C Wei, Jue Feng, Jason Kurzer, Corina Schneidawind, Stephen H K Wong, Michael C Bassik, Michael L Cleary
There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the fusion protein E2A-PBX1, which is present in 5-7% of pediatric and 50% of pre-B-cell receptor (preBCR+) acute lymphocytic leukemia (ALL). In this study, we describe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL which result in hyperactivation of the key oncogenic effector enzyme PLCγ2...
October 7, 2016: Cancer Research
Hubo Li, Brenton G Mar, Huadi Zhang, Rishi V Puram, Francisca Vazquez, Barbara A Weir, William C Hahn, Benjamin Ebert, David Pellman
Acute myeloid leukemia (AML) is a heterogeneous disease with complex molecular pathophysiology. To systematically characterize AML's genetic dependencies, we conducted genome-scale shRNA screens in 17 AML cell lines and analyzed dependencies relative to parallel screens in 199 cell lines of other cancer types. We identified 353 genes specifically required for AML cell proliferation. To validate the in vivo relevance of genetic dependencies observed in human cell lines, we performed a secondary screen in a syngeneic murine AML model driven by the MLL-AF9 oncogenic fusion protein...
October 18, 2016: Blood
Stephen J Goldie, Benedicta D Arhatari, Peter Anderson, Alana Auden, Darren D Partridge, Stephen M Jane, Sebastian Dworkin
BACKGROUND: Increased apposition of the frontal and parietal bones of the skull during embryogenesis may be a risk factor for the subsequent development of premature skull fusion, or craniosynostosis. Human craniosynostosis is a prevalent, and often serious embryological and neonatal pathology. Other than known mutations in a small number of contributing genes, the aetiology of craniosynostosis is largely unknown. Therefore, the identification of novel genes which contribute to normal skull patterning, morphology and premature suture apposition is imperative, in order to fully understand the genetic regulation of cranial development...
October 18, 2016: BMC Developmental Biology
Masaaki Ikeda, Yoshitaka Yoshimura, Takashi Kikuiri, Mino Matsuno, Tomokazu Hasegawa, Kumu Fukushima, Takako Hayakawa, Hajime Minamikawa, Kuniaki Suzuki, Junichiro Iida
Bone remodeling is an important factor in orthodontic tooth movement. During orthodontic treatment, osteoclasts are subjected to various mechanical stimuli, and this promotes or inhibits osteoclast differentiation and fusion. It has been previously reported that the release from tensile force induces osteoclast differentiation. However, little is known about how release from compressive force affects osteoclasts. The present study investigated the effects of release from compressive force on osteoclasts. The number of tartrate‑resistant acid phosphatase (TRAP)‑positive multinucleated osteoclasts derived from RAW264...
October 5, 2016: Molecular Medicine Reports
John G Conboy
The Rbfox genes encode an ancient family of sequence-specific RNA binding proteins (RBPs) that are critical developmental regulators in multiple tissues including skeletal muscle, cardiac muscle, and brain. The hallmark of Rbfox proteins is a single high-affinity RRM domain, highly conserved from insects to humans, that binds preferentially to UGCAUG motifs at diverse regulatory sites in pre-mRNA introns, mRNA 3'UTRs, and pre-miRNAs hairpin structures. Versatile regulatory circuits operate on Rbfox pre-mRNA and mRNA to ensure proper expression of Rbfox1 protein isoforms, which then act on the broader transcriptome to regulate alternative splicing networks, mRNA stability and translation, and microRNA processing...
October 17, 2016: Wiley Interdisciplinary Reviews. RNA
Yangdong Sun, Qiao Ye, Min Wu, Yonghong Wu, Chenggang Zhang, Weiqun Yan
This study aimed to validate the high yield and soluble expression of proteins carrying the transactivator of transcription (Tat) peptide tag, and further explored the potential mechanism by which the Tat tag increases expression. Escherichia coli superoxide dismutase (SOD) proteins, including SodA, SodB and SodC, were selected for analysis. As expected, the yields and the solubility of Tat-tagged proteins were higher than those of Tat-free proteins, and similar results were observed for the total SOD enzyme activity...
October 14, 2016: Experimental & Molecular Medicine
Hongjiu Yu, Yonggui Ge, Lianying Guo, Lin Huang
Ewing's sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise...
October 11, 2016: Oncotarget
Kazuki Okamoto, Shizu Hirata-Tsuchiya, Chiaki Kitamura, Kazuki Omoteyama, Toshiyuki Sato, Mitsumi Arito, Manae S Kurokawa, Naoya Suematsu, Tomohiro Kato
Nuclear factor-κB (NF-κB) is the most potent pro-inflammatory transactivator, and an inhibitor of NF-κB is a good anti-inflammatory drug. Glucocorticoids (GCs) are the strongest and the most frequently used anti-inflammatory drugs. GCs-bound glucocorticoid receptor (GR) inhibits the transcriptional activity of NF-κB, and thereby suppresses a broad range of inflammatory processes. Concurrently, in whole body out side of inflammation area, GR exerts a lot of hormone action, which results in severe side effects...
October 14, 2016: Endocrinology
Limin Zhang, Tao Jiang, Chao Zhao, Wei Li, Xuefei Li, Sha Zhao, Xiaozhen Liu, Yijun Jia, Hui Yang, Shengxiang Ren, Caicun Zhou
BACKGROUND: ROS1 rearrangement is a novel molecular subgroup of non-small-cell lung cancer (NSCLC). This study aimed to investigate the efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement. RESULTS: A total of 2309 patients received ROS1 fusion detection and 51(2.2%) patients had ROS1 rearrangement. There was no significant difference between ROS1 fusion-positive and fusion-negative cohorts in demographic data...
October 12, 2016: Oncotarget
Dirk Landgraf, Dann Huh, Erinc Hallacli, Susan Lindquist
Gene tagging with fluorescent proteins is commonly applied to investigate the localization and dynamics of proteins in their cellular environment. Ideally, a fluorescent tag is genetically inserted at the endogenous locus at the N- or C- terminus of the gene of interest without disrupting regulatory sequences including the 5' and 3' untranslated region (UTR) and without introducing any extraneous unwanted "scar" sequences, which may create unpredictable transcriptional or translational effects. We present a reliable, low-cost, and highly efficient method for the construction of such scarless C-terminal and N-terminal fusions with fluorescent proteins in yeast...
2016: PloS One
Kamil Kowalski, Aleksandra Kołodziejczyk, Maria Helena Sikorska, Jagoda Płaczkiewicz, Paulina Cichosz, Magdalena Kowalewska, Wladyslawa Streminska, Katarzyna Janczyk-Ilach, Marta Koblowska, Anna Fogtman, Roksana Iwanicka-Nowicka, Maria A Ciemerych, Edyta Brzoska
The skeletal muscle regeneration occurs due to the presence of tissue specific stem cells - satellite cells. These cells, localized between sarcolemma and basal lamina, are bound to muscle fibers and remain quiescent until their activation upon muscle injury. Due to pathological conditions, such as extensive injury or dystrophy, skeletal muscle regeneration is diminished. Among the therapies aiming to ameliorate skeletal muscle diseases are transplantations of the stem cells. In our previous studies we showed that Sdf-1 (stromal derived factor -1) increased migration of stem cells and their fusion with myoblasts in vitro...
October 13, 2016: Cell Adhesion & Migration
Lu Yu, Jun Li, Sanpeng Xu, Mariajose Navia Miranda, Guoping Wang, Yaqi Duan
BACKGROUND: Xp11.2 translocation/transcription factor E3 (TFE3) rearrangement renal cell carcinoma (RCC) is a rare subtype of RCC with limited clinical and pathological data. CASE PRESENTATION: Here we present an unusual high-grade Xp11.2 translocation RCC with a rhabdoid feature and SMARCB1 (INI1) inactivation in a 40-year-old man with end-stage kidney disease. The histological examination of the dissected left renal tumor showed an organoid architecture of the eosinophilic or clear neoplastic cells with necrosis and high mitotic activity...
October 12, 2016: Diagnostic Pathology
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