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https://www.readbyqxmd.com/read/29743362/adenovirus-5-e1a-mediated-suppression-of-p53-via-fubp1
#1
Jasmine Rae Frost, Megan Mendez, Andrea Michelle Soriano, Leandro Crisostomo, Oladunni Olanubi, Sandi Radko, Peter Pelka
The Far Upstream Element Binding Protein 1 (FUBP1) was first identified as a regulator of the oncogene c-Myc via binding to the Far Upstream Element (FUSE) within the c-Myc promoter and activating expression of the gene. Recent studies have identified FUBP1 as a regulator of transcription, translation, and splicing via its DNA and RNA binding activities. Here we report the identification of FUBP1 as a novel binding partner of E1A. FUBP1 binds directly to E1A via the N-terminus (residues 1-82) and Conserved Region 3 (residues 139 to 204) of adenovirus 5 E1A...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29713041/rna-sequencing-of-xp11-translocation-associated-cancers-reveals-novel-gene-fusions-and-distinctive-clinicopathologic-correlations
#2
Xiao-Tong Wang, Qiu-Yuan Xia, Sheng-Bing Ye, Xuan Wang, Rui Li, Ru Fang, Shan-Shan Shi, Ru-Song Zhang, Xiao Tan, Jie-Yu Chen, Ke Sun, Xiao-Dong Teng, Heng-Hui Ma, Zhen-Feng Lu, Xiao-Jun Zhou, Qiu Rao
Both Xp11 translocation renal cell carcinomas and the corresponding mesenchymal neoplasms are characterized by a variety of gene fusions involving TFE3. It has been known that tumors with different gene fusions may have different clinicopathologic features; however, further in-depth investigations of subtyping Xp11 translocation-associated cancers are needed in order to explore more meaningful clinicopathologic correlations. A total of 22 unusual cases of Xp11 translocation-associated cancers were selected for the current study; 20 cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners...
April 30, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29712837/mechanistic-studies-of-a-small-molecule-modulator-of-smn2-splicing
#3
Jingxin Wang, Peter G Schultz, Kristen A Johnson
RG-7916 is a first-in-class drug candidate for the treatment of spinal muscular atrophy (SMA) that functions by modulating pre-mRNA splicing of the SMN2 gene, resulting in a 2.5-fold increase in survival of motor neuron (SMN) protein level, a key protein lacking in SMA patients. RG-7916 is currently in three interventional phase 2 clinical trials for various types of SMA. In this report, we show that SMN-C2 and -C3, close analogs of RG-7916, act as selective RNA-binding ligands that modulate pre-mRNA splicing...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29643205/in-vitro-iclip-based-modeling-uncovers-how-the-splicing-factor-u2af2-relies-on-regulation-by-cofactors
#4
F X Reymond Sutandy, Stefanie Ebersberger, Lu Huang, Anke Busch, Maximilian Bach, Hyun-Seo Kang, Jörg Fallmann, Daniel Maticzka, Rolf Backofen, Peter F Stadler, Kathi Zarnack, Michael Sattler, Stefan Legewie, Julian König
Alternative splicing generates distinct mRNA isoforms and is crucial for proteome diversity in eukaryotes. The RNA-binding protein (RBP) U2AF2 is central to splicing decisions, as it recognizes 3' splice sites and recruits the spliceosome. We establish "in vitro iCLIP" experiments, in which recombinant RBPs are incubated with long transcripts, to study how U2AF2 recognizes RNA sequences and how this is modulated by trans -acting RBPs. We measure U2AF2 affinities at hundreds of binding sites and compare in vitro and in vivo binding landscapes by mathematical modeling...
April 11, 2018: Genome Research
https://www.readbyqxmd.com/read/29606613/far-upstream-element-binding-protein-1-regulates-lsd1-alternative-splicing-to-promote-terminal-differentiation-of-neural-progenitors
#5
Inah Hwang, Dongqing Cao, Yoonmi Na, Do-Yeon Kim, Tuo Zhang, Jun Yao, Hwanhee Oh, Jian Hu, Hongwu Zheng, Yu Yao, Jihye Paik
Loss of a cell's ability to terminally differentiate because of mutations is a selected genetic event in tumorigenesis. Genomic analyses of low-grade glioma have reported recurrent mutations of far upstream element-binding protein 1 (FUBP1). Here, we show that FUBP1 expression is dynamically regulated during neurogenesis and that its downregulation in neural progenitors impairs terminal differentiation and promotes tumorigenesis collaboratively with expression of IDH1R132H . Mechanistically, collaborative action between SRRM4 and FUBP1 is necessary for mini-exon splicing of the neurospecific LSD1+8a isoform...
March 21, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29521646/incorporating-advances-in-molecular-pathology-into-brain-tumor-diagnostics
#6
José E Velázquez Vega, Daniel J Brat
Recent advances in molecular pathology have reshaped the practice of brain tumor diagnostics. The classification of gliomas has been restructured with the discovery of isocitrate dehydrogenase (IDH) 1/2 mutations in the vast majority of lower grade infiltrating gliomas and secondary glioblastomas (GBM), with IDH-mutant astrocytomas further characterized by TP53 and ATRX mutations. Whole-arm 1p/19q codeletion in conjunction with IDH mutations now define oligodendrogliomas, which are also enriched for CIC, FUBP1, PI3K, NOTCH1, and TERT-p mutations...
May 2018: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/29150923/pkg-ii-effectively-reversed-egf-induced-protein-expression-alterations-in-human-gastric-cancer-cell-lines
#7
Hai Qian, Yan Tao, Lu Jiang, Ying Wang, Ting Lan, Min Wu, Ji Pang, Kwaku Appiah-Kubi, Yongchang Chen, Yan Wu
Epidermal growth factor receptor (EGFR) plays an important role in gastric cancer (GC) progression. Our previous data demonstrated that type II cGMP-dependent protein kinase (PKG II) could block the EGF-EGFR axis as well as down-stream signaling pathways for example, MAPK, PI3K and PLC in gastric cancer cells. However, the exact mechanisms of PKG II against cancer remain unclear. Therefore, the present work was to address the above question. Human gastric cancer cell line AGS was infected with adenoviral construct encoding cDNA of PKG II (Ad-PKG II) to up-regulate PKG II and then treated with 8-pCPT-cGMP...
November 18, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29133573/the-rars-mad1l1-fusion-gene-induces-cancer-stem-cell-like-properties-and-therapeutic-resistance-in-nasopharyngeal-carcinoma
#8
Qian Zhong, Zhi-Hua Liu, Zhi-Rui Lin, Ze-Dong Hu, Li Yuan, Yan-Min Liu, Ai-Jun Zhou, Li-Hua Xu, Li-Juan Hu, Zi-Feng Wang, Xin-Yuan Guan, Jia-Jie Hao, Vivian W Y Lui, Ling Guo, Hai-Qiang Mai, Ming-Yuan Chen, Fei Han, Yun-Fei Xia, Jennifer R Grandis, Xing Zhang, Mu-Sheng Zeng
Purpose: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC. Experimental Design: RNA sequencing (RNA-seq) was applied to look for interchromosome translocation in NPC. PCR, FISH, and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies...
February 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29031818/camptothecin-and-its-analog-sn-38-the-active-metabolite-of-irinotecan-inhibit-binding-of-the-transcriptional-regulator-and-oncoprotein-fubp1-to-its-dna-target-sequence-fuse
#9
Sabrina Khageh Hosseini, Stefanie Kolterer, Marlene Steiner, Viktoria von Manstein, Katharina Gerlach, Jörg Trojan, Oliver Waidmann, Stefan Zeuzem, Jörg O Schulze, Steffen Hahn, Dieter Steinhilber, Volker Gatterdam, Robert Tampé, Ricardo M Biondi, Ewgenij Proschak, Martin Zörnig
The transcriptional regulator FUSE Binding Protein 1 (FUBP1) is overexpressed in more than 80% of all human hepatocellular carcinomas (HCCs) and other solid tumor entities including prostate and colorectal carcinoma. FUBP1 expression is required for HCC tumor cell expansion, and it functions as an important pro-proliferative and anti-apoptotic oncoprotein that binds to the single-stranded DNA sequence FUSE to regulate the transcription of a variety of target genes. In this study, we screened an FDA-approved drug library and discovered that the Topoisomerase I (TOP1) inhibitor camptothecin (CPT) and its derivative 7-ethyl-10-hydroxycamptothecin (SN-38), the active irinotecan metabolite that is used in the clinics in combination with other chemotherapeutics to treat carcinoma, inhibit FUBP1 activity...
December 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28825722/the-long-noncoding-rna-snhg1-promotes-tumor-growth-through-regulating-transcription-of-both-local-and-distal-genes
#10
Y Sun, G Wei, H Luo, W Wu, G Skogerbø, J Luo, R Chen
Increasing evidence indicates that long noncoding RNAs (lncRNAs) have important roles in various physiological processes and dysfunction of lncRNAs could be a prevalent cause in human diseases. Here we functionally characterized the nuclear-enriched lncRNA SNHG1, which is highly expressed in multiple types of cancer. We also provide evidence that SNHG1 promotes cancer cell growth by regulating gene expression both in cis and in trans. SNHG1 was involved in the AKT signaling pathway as it promotes the neighboring transcription of the protein-coding gene SLC3A2 in cis by binding the Mediator complex to facilitate the establishment of enhancer-promoter interaction...
December 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28780352/expression-of-far-upstream-element-binding-protein-1-correlates-with-c-myc-expression-in-sacral-chordomas-and-is-associated-with-tumor-progression-and-poor-prognosis
#11
Hai Wen, Hong Ma, Pengzhi Li, Jiaoyun Zheng, Yipin Yu, Guohua Lv
The far upstream element (FUSE)-binding protein 1 (FUBP1), a well-known transcriptional regulator of the proto-oncogene c-Myc, has been demonstrated by previous work to be aberrantly expressed in a variety of tumors and plays a critical role in tumor progression; however, its expression and function in relatively rare and aggressive chordomas remains unclear. In this retrospective study, we reviewed clinicopathologic characteristics of 40 patients diagnosed with sacral chordoma, and analyzed 40 tumor and 20 distant normal tissues obtained from patients during the primary surgical tumor excision...
September 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28768910/sexual-dimorphism-in-glioma-glycolysis-underlies-sex-differences-in-survival
#12
Joseph E Ippolito, Aldrin Kay-Yuen Yim, Jingqin Luo, Prakash Chinnaiyan, Joshua B Rubin
The molecular bases for sex differences in cancer remain undefined and how to incorporate them into risk stratification remains undetermined. Given sex differences in metabolism and the inverse correlation between fluorodeoxyglucose (FDG) uptake and survival, we hypothesized that glycolytic phenotyping would improve glioma subtyping. Using retrospectively acquired lower-grade glioma (LGG) transcriptome data from The Cancer Genome Atlas (TCGA), we discovered male-specific decreased survival resulting from glycolytic gene overexpression...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28667493/mir-16-1-targeted-silences-far-upstream-element-binding-protein-1-to-advance-the-chemosensitivity-to-adriamycin-in-gastric-cancer
#13
Danyi Zhao, Yang Zhang, Lei Song
Chemotherapy can prevent metastasis and recurrence of gastric cancer (GC), and is a well supplement for operation. But, chemotherapy resistance has severely restricted the application of chemotherapy. This study aimed to investigate the regulatory roles and molecular mechanism of miR-16-1 to the chemosensitivity to adriamycin in GC. In this study, the expression of miR-16-1 and FUBP1 was down-regulated and up-regulated respectively in adriamycin-resistant GC tissues and cell lines, and represented a negative relationship between them...
June 30, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28588622/delayed-mesoderm-and-erythroid-differentiation-of-murine-embryonic-stem-cells-in-the-absence-of-the-transcriptional-regulator-fubp1
#14
Josephine Wesely, Marlene Steiner, Frank Schnütgen, Manuel Kaulich, Michael A Rieger, Martin Zörnig
The transcriptional regulator far upstream binding protein 1 (FUBP1) is essential for fetal and adult hematopoietic stem cell (HSC) self-renewal, and the constitutive absence of FUBP1 activity during early development leads to embryonic lethality in homozygous mutant mice. To investigate the role of FUBP1 in murine embryonic stem cells (ESCs) and in particular during differentiation into hematopoietic lineages, we generated Fubp1 knockout (KO) ESC clones using CRISPR/Cas9 technology. Although FUBP1 is expressed in undifferentiated ESCs and during spontaneous differentiation following aggregation into embryoid bodies (EBs), absence of FUBP1 did not affect ESC maintenance...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28535583/molecular-testing-of-brain-tumor
#15
REVIEW
Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi
The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53 , and ATRX , oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC , FUBP1 , and the promoter region of telomerase reverse transcriptase ( TERTp )...
May 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28472509/multicenter-phase-ii-study-of-temozolomide-and-myeloablative-chemotherapy-with-autologous-stem-cell-transplant-for-newly-diagnosed-anaplastic-oligodendroglioma
#16
Alissa A Thomas, Lauren E Abrey, Robert Terziev, Jeffrey Raizer, Nina L Martinez, Peter Forsyth, Nina Paleologos, Matthew Matasar, Craig S Sauter, Craig Moskowitz, Stephen D Nimer, Lisa M DeAngelis, Thomas Kaley, Sean Grimm, David N Louis, J Gregory Cairncross, Katherine S Panageas, Samuel Briggs, Geraldine Faivre, Nimish A Mohile, Jayesh Mehta, Philip Jonsson, Debyani Chakravarty, Jianjiong Gao, Nikolaus Schultz, Cameron W Brennan, Jason T Huse, Antonio Omuro
Background: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy. Methods: Patients with AO/AOA received 6 cycles of TMZ (200 mg/m2 × 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m2/day × 3 days, then busulfan 3...
October 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28388591/genetic-landscape-of-extreme-responders-with-anaplastic-oligodendroglioma
#17
Matthias Holdhoff, Gregory J Cairncross, Thomas M Kollmeyer, Ming Zhang, Peixin Zhang, Minesh P Mehta, Maria Werner-Wasik, Luis Souhami, Jean-Paul Bahary, Young Kwok, Alan C Hartford, Arnab Chakravarti, Srinivasan Yegnasubramanian, Bert Vogelstein, Nickolas Papadopoulos, Kenneth Kinzler, Robert B Jenkins, Chetan Bettegowda
BACKGROUND: The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not. METHODS: We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28381186/the-expression-pattern-of-long-non-coding-rna-pvt1-in-tumor-tissues-and-in-extracellular-vesicles-of-colorectal-cancer-correlates-with-cancer-progression
#18
Kai Guo, Jie Yao, Qiang Yu, Zijian Li, Hu Huang, Jianguo Cheng, Zhigang Wang, Yunfeng Zhu
The plasmacytoma variant translocation 1 gene (PVT1) is a large non-coding locus at adjacent of c-Myc, and long non-coding RNA PVT1 is now recognized as a cancerous gene co-amplified with c-Myc in various cancers. But the expression and functional role of PVT1 in colorectal cancer are still unelucidated. In addition, all the reported long non-coding RNAs so far are discovered in either cells or tissues, but no research about long non-coding RNAs detection in extracellular vesicles has been reported yet. In the present study, we firstly investigated the expression of PVT1 in colorectal cancer specimens and its correlation with the expression of c-Myc and other related genes by real-time polymerase chain reaction...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28270234/genetic-and-epigenetic-stability-of-oligodendrogliomas-at-recurrence
#19
Koki Aihara, Akitake Mukasa, Genta Nagae, Masashi Nomura, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Junji Shibahara, Miwako Takahashi, Toshimitsu Momose, Shota Tanaka, Shunsaku Takayanagi, Shunsuke Yanagisawa, Takahide Nejo, Satoshi Takahashi, Mayu Omata, Ryohei Otani, Kuniaki Saito, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Hiroyuki Aburatani, Nobuhito Saito
Among diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients...
March 7, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28170390/multiscale-mutation-clustering-algorithm-identifies-pan-cancer-mutational-clusters-associated-with-pathway-level-changes-in-gene-expression
#20
William Poole, Kalle Leinonen, Ilya Shmulevich, Theo A Knijnenburg, Brady Bernard
Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters...
February 2017: PLoS Computational Biology
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