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https://www.readbyqxmd.com/read/29328432/a-double-edged-function-of-ddx3-as-an-oncogene-or-tumor-suppressor-in-cancer-progression-review
#1
Yu He, Dan Zhang, Yanfang Yang, Xixi Wang, Xinyu Zhao, Peng Zhang, Hongxia Zhu, Ningzhi Xu, Shufang Liang
DEAD-box RNA helicase 3 (DDX3) is a highly conserved family member of DEAD-box proteins in all eukaryotes from yeasts to human beings. Accumulating studies have confirmed DDX3 has the ability to regulate different steps of RNA metabolism, including RNA splicing, RNA export, transcription and translation initiation. Moreover, DDX3 is involved in many biological processes, such as stress response, cell apoptosis, cell cycle regulation and virus infection. In recent years, DDX3 is getting increasing attention due to its essential roles in cancer progression...
January 9, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29323119/cug-initiation-and-frameshifting-enable-production-of-dipeptide-repeat-proteins-from-als-ftd-c9orf72-transcripts
#2
Ricardos Tabet, Laure Schaeffer, Fernande Freyermuth, Melanie Jambeau, Michael Workman, Chao-Zong Lee, Chun-Chia Lin, Jie Jiang, Karen Jansen-West, Hussein Abou-Hamdan, Laurent Désaubry, Tania Gendron, Leonard Petrucelli, Franck Martin, Clotilde Lagier-Tourenne
Expansion of G4C2 repeats in the C9ORF72 gene is the most prevalent inherited form of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded transcripts undergo repeat-associated non-AUG (RAN) translation producing dipeptide repeat proteins from all reading frames. We determined cis-factors and trans-factors influencing translation of the human C9ORF72 transcripts. G4C2 translation operates through a 5'-3' cap-dependent scanning mechanism, requiring a CUG codon located upstream of the repeats and an initiator Met-tRNAMeti...
January 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29319382/ctc-derived-ar-v7-detection-as-a-prognostic-and-predictive-biomarker-in-advanced-prostate-cancer
#3
Diogo A Bastos, Emmanuel S Antonarakis
Prostate cancer is a highly heterogeneous disease, with remarkably different prognosis across all stages. Increased circulating tumor cell (CTC) count (≥ 5) using the CellSearch assay has been identified as one of the markers that can be used to predict survival, with added value beyond currently available prognostic factors. Recently, androgen receptor splice variant 7 (AR-V7) detection has been associated with worse outcomes for patients with castration-resistant prostate cancer (CRPC) treated with novel androgen receptor-signaling (ARS) inhibitors such as abiraterone and enzalutamide but not taxane chemotherapies...
January 10, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29316036/inhibition-of-ire1-results-in-decreased-scar-formation
#4
Tatiana V Boyko, Rakesh Bam, Dadi Jiang, Zhen Wang, Namrata Bhatia, Misha C Tran, Michael T Longaker, Albert C Koong, George P Yang
Wound healing is characterized by the production of large amounts of protein necessary to replace lost cellular mass and extracellular matrix. The unfolded protein response (UPR) is an important adaptive cellular response to increased protein synthesis. One of the main components of the UPR is IRE1, an ER transmembrane protein with endonuclease activity that produces the activated form of the transcription factor XBP1. Using luciferase reporter mice for Xbp1 splicing, we showed that IRE1 was up-regulated during excisional wound healing at the time in wound healing consistent with that of the proliferative phase, when the majority of protein synthesis for cellular proliferation and matrix deposition occurs...
January 8, 2018: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29285362/dtcapfs-a-derivative-of-a-novel-human-hormone-peptide-induces-apoptosis-in-cancer-cells-through-a-mechanism-involving-loss-of-golgi-function
#5
Joel Ohana, Uziel Sandler, Gideon Kass, Salomon M Stemmer, Yoram Devary
dTCApFs (Nerofe™) is a 14-amino acid derivative of a longer hormone peptide, tumor-cells apoptosis factor (TCApF), which enters the cells through the T1/ST2 receptor. In the present study, the mechanism of action (MOA) of dTCApFs as an anticancer agent was investigated. Experiments were performed in pancreatic cancer cell lines, and immunofluorescent staining demonstrated that dTCApFs is located in the Golgi apparatus of treated cells. It was also demonstrated in pancreatic, breast and ovarian cell lines that dTCApFs treatment led to Golgi structural changes, loss of Golgi function, and molecular effects associated with endoplasmic reticulum (ER) stress, such as increased levels of C/EBP homologous protein, binding immunoglobulin protein (BiP), phosphorylated inositol-requiring enzyme 1 (pIRE1), and increased phosphorylation of eukaryotic translation initiation factor 2α, and to the generation of reactive oxygen species, which was attenuated by ER stress inhibitors...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29285262/nuclear-membrane-localised-nox4d-generates-pro-survival-ros-in-flt3-itd-expressing-aml
#6
Jennifer N Moloney, Ashok Kumar Jayavelu, Joanna Stanicka, Sarah L Roche, Rebecca L O'Brien, Sebastian Scholl, Frank-D Böhmer, Thomas G Cotter
Internal tandem duplication of the juxtamembrane domain of FMS-like tyrosine kinase 3 (FLT3-ITD) is the most prevalent genetic aberration present in 20-30% of acute myeloid leukaemia (AML) cases and is associated with a poor prognosis. FLT3-ITD expressing cells express elevated levels of NADPH oxidase 4 (NOX4)-generated pro-survival hydrogen peroxide (H2O2) contributing to increased levels of DNA oxidation and double strand breaks. NOX4 is constitutively active and has been found to have various isoforms expressed at multiple locations within a cell...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29280214/thorough-in-silico-and-in-vitro-cdna-analysis-of-21-putative-brca1-and-brca2-splice-variants-and-a-complex-tandem-duplication-in-brca2-allowing-the-identification-of-activated-cryptic-splice-donor-sites-in-brca2-exon-11
#7
Annelot Baert, Eva Machackova, Ilse Coene, Carol Cremin, Kristin Turner, Cheryl Portigal-Todd, Marie Jill Asrat, Jennifer Nuk, Allison Mindlin, Young Sean, Andree MacMillan, Tom Van Maerken, Martin Trbusek, Wendy McKinnon, Marie E Wood, William D Foulkes, Marta Santamariña, Miguel de la Hoya, Lenka Foretova, Bruce Poppe, Anne Vral, Toon Rosseel, Kim De Leeneer, Ana Vega, Kathleen B M Claes
For 21 putative BRCA1 and BRCA2 splice site variants the concordance between mRNA analysis and predictions by in silico programs was evaluated. Aberrant splicing was confirmed for 12 alterations. In silico prediction tools were helpful to determine for which variants cDNA analysis is warranted, however, predictions for variants in the Cartegni consensus region but outside the canonical sites, were less reliable. Learning algorithms like Adaboost and Random Forest outperformed the classical tools. Further validations are warranted prior to implement these novel tools in clinical settings...
December 27, 2017: Human Mutation
https://www.readbyqxmd.com/read/29259843/tris-1-3-dichloro-2-propyl-phosphate-disrupts-dorsoventral-patterning-in-zebrafish-embryos
#8
Subham Dasgupta, Sara M Vliet, Allison Kupsco, Jessica K Leet, Diego Altomare, David C Volz
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a high-production volume organophosphate flame retardant widely used within the United States. Within zebrafish, initiation of TDCIPP exposure at 0.75 h post-fertilization (hpf) results in genome-wide alterations in methylation during cleavage (2 hpf) as well as epiboly delay or arrest (at higher concentrations) during late-blastula and early-gastrula (4-6 hpf). To determine whether these TDCIPP-induced effects were associated with impacts on the transcriptome, embryos were exposed to vehicle (0...
2017: PeerJ
https://www.readbyqxmd.com/read/29243324/validation-of-histone-deacetylase-3-as-a-therapeutic-target-in-castration-resistant-prostate-cancer
#9
Abigail B McLeod, James P Stice, Suzanne E Wardell, Holly M Alley, Ching-Yi Chang, Donald P McDonnell
BACKGROUND: Whereas the androgen receptor (AR) signaling axis remains a therapeutic target in castration-resistant prostate cancer (CRPC), the emergence of AR mutations and splice variants as mechanisms underlying resistance to contemporary inhibitors of this pathway highlights the need for new therapeutic approaches to target this disease. Of significance in this regard is the considerable preclinical data, indicating that histone deacetylase (HDAC) inhibitors may have utility in the treatment of CRPC...
December 15, 2017: Prostate
https://www.readbyqxmd.com/read/29238599/characterization-of-physiological-and-molecular-processes-associated-with-potato-response-to-zebra-chip-disease
#10
Chika C Nwugo, Venkatesan G Sengoda, Li Tian, Hong Lin
Transcriptional analyses identified molecular mechanisms associated with the response of leaf and root potato tissues to 'Candidatus. Liberibacter solanacearum' (Lso) infection, presumptive causal agent of zebra chip disease (ZC). Putative Lso infection affected several host processes including defense response-, regulation-, starch metabolism- and energy production-related processes. Interestingly, while proteinase inhibitors were strongly upregulated in leaf tissues, a concomitant downregulation was observed in root tissues...
2017: Horticulture Research
https://www.readbyqxmd.com/read/29236940/polyclonal-rb1-mutations-and-acquired-resistance-to-cdk-4-6-inhibitors-in-patients-with-metastatic-breast-cancer
#11
R Condorelli, L Spring, J O'Shaughnessy, L Lacroix, C Bailleux, V Scott, J Dubois, R J Nagy, R B Lanman, A J Iafrate, F Andre, A Bardia
Background: While deregulation of the cyclin D1-CDK4/6-retinoblastoma pathway is common in hormone receptor positive (HR+) breast cancer, Rb is usually intact in HR+ breast cancer, and targeted CDK 4/6 inhibitors that act upstream of Rb, are routinely being utilized in clinical practice. However, factors that can lead to clinical resistance to CDK 4/6 inhibitors are not known. Patients and methods: We identified patients who had pre and post genotyping in tissue and peripheral blood samples after receiving CDK 4/6 inhibitors...
December 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29235382/exploiting-differential-rna-splicing-patterns-a-potential-new-group-of-therapeutic-targets-in-cancer
#12
Nidhi Jyotsana, Michael Heuser
Mutations in genes associated with splicing have been found in hematologic malignancies, but also in solid cancers. Aberrant cancer specific RNA splicing either results from mutations or misexpression of the spliceosome genes directly, or from mutations in splice sites of oncogenes or tumor suppressors. Areas covered: In this review, we present molecular targets of aberrant splicing in various malignancies, information on existing and emerging therapeutics against such targets, and strategies for future drug development...
December 13, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29233683/caspase-mediated-cleavage-of-x-ray-repair-cross-complementing-group-4-promotes-apoptosis-by-enhancing-nuclear-translocation-of-caspase-activated-dnase
#13
Yumi Sunatani, Radhika Pankaj Kamdar, Mukesh Kumar Sharma, Tadashi Matsui, Ryo Sakasai, Mitsumasa Hashimoto, Yasuhito Ishigaki, Yoshihisa Matsumoto, Kuniyoshi Iwabuchi
X-ray repair cross-complementing group 4 (XRCC4), a repair protein for DNA double-strand breaks, is cleaved by caspases during apoptosis. In this study, we examined the role of XRCC4 in apoptosis. Cell lines, derived from XRCC4-deficient M10 mouse lymphoma cells and stably expressing wild-type XRCC4 or caspase-resistant XRCC4, were established and treated with staurosporine (STS) to induce apoptosis. In STS-induced apoptosis, expression of wild-type, but not caspase-resistant, XRCC4 in XRCC4-deficient cells enhanced oligonucleosomal DNA fragmentation and the appearance of TUNEL-positive cells by promoting nuclear translocation of caspase-activated DNase (CAD), a major nuclease for oligonucleosomal DNA fragmentation...
December 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29229447/hnrnp-a1-promotes-keratinocyte-cell-survival-post-uvb-radiation-through-pi3k-akt-mtor-pathway
#14
Jianguo Feng, Yi Liao, Xichao Xu, Qian Yi, Ling He, Liling Tang
hnRNP A1 acts as a critical splicing factor in regulating many alternative splicing events in various physiological and pathophysiological progressions. hnRNP A1 is capable of regulating UVB-induced hdm2 gene alternative splicing according to our previous study. However, the biological function and underlying molecular mechanism of hnRNP A1 in cell survival and cell cycle in response to UVB irradiation are still unclear. In this study, silencing hnRNP A1 expression by siRNA transfection led to decreased cell survival after UVB treatment, while promoting hnRNP A1 by lentiviruse vector resulted in increased cell survival...
December 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29212152/prpf8-is-important-for-brca1-mediated-homologous-recombination
#15
David O Onyango, Gabriella Lee, Jeremy M Stark
Disruption of RNA splicing causes genome instability, which could contribute to cancer etiology. Furthermore, RNA splicing is an emerging anti-cancer target. Thus, we have evaluated the influence of the spliceosome factor PRPF8 and the splicing inhibitor Pladienolide B (PlaB) on homologous recombination (HR). We find that PRPF8 depletion and PlaB treatment cause a specific defect in homology-directed repair (HDR), and single strand annealing (SSA), which share end resection as a common intermediate, and BRCA1 as a required factor...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211299/endoplasmic-reticulum-stress-induced-lox-1-cd15-polymorphonuclear-myeloid-derived-suppressor-cells-in-hepatocellular-carcinoma
#16
Nan Jiang, Yan-Fang Xing, Bo Hu, Jian-Xin Tang, Hui-Min Dong, Yu-Mei He, Dan-Yun Ruan, Qing-Jian Ye, Jia-Rong Cai, Xiao-Kun Ma, Jie Chen, Xiu-Rong Cai, Ze-Xiao Lin, Xiang-Yuan Wu, Xing Li
AIM: A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphonuclears myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. METHODS: 127 HCC patients, 10 patients with mild active chronic hepatits B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included...
December 6, 2017: Immunology
https://www.readbyqxmd.com/read/29197031/preclinical-evaluation-of-the-aurora-kinase-inhibitors-amg-900-azd1152-hqpa-and-mk-5108-on-sw-872-and-93t449-human-liposarcoma-cells
#17
Sandhya Noronha, Lauren A C Alt, Taylor E Scimeca, Omran Zarou, Justyna Obrzut, Brian Zanotti, Elizabeth A Hayward, Akhil Pillai, Shubha Mathur, Joseph Rojas, Ribhi Salamah, Nalini Chandar, Michael J Fay
Liposarcoma is a malignant soft tissue tumor that originates from adipose tissue and is one of the most frequently diagnosed soft tissue sarcomas in humans. There is great interest in identifying novel chemotherapeutic options for treating liposarcoma based upon molecular alterations in the cancer cells. The Aurora kinases have been identified as promising chemotherapeutic targets based on their altered expression in many human cancers and cellular roles in mitosis and cytokinesis. In this study, we investigated the effects of an Aurora kinase A inhibitor (MK-5108), an Aurora kinase B inhibitor (AZD1152-HQPA), and a pan-Aurora kinase inhibitor (AMG 900) on undifferentiated SW-872 and well-differentiated 93T449 human liposarcoma cells...
December 1, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/29171936/braf-internal-deletions-and-resistance-to-braf-mek-inhibitor-therapy
#18
Douglas B Johnson, Merrida A Childress, Zachary R Chalmers, Garrett M Frampton, Siraj M Ali, Samuel M Rubinstein, David Fabrizio, Jeffrey S Ross, Sohail Balasubramanian, Vincent A Miller, Philip J Stephens, Jeffrey A Sosman, Christine M Lovly
BRAF and MEK inhibitors have improved clinical outcomes in advanced, BRAFV600 - mutated melanomas. Acquired resistance occurs in most patients, with numerous and diverse drivers. We obtained pre-treatment and progression biopsies from a patient who progressed on dabrafenib and trametinib. In addition to a preserved BRAFV600E mutation, an internal deletion (rearrangement) of BRAF was observed in the progression sample. This deletion involved exons 2-8, which includes the Ras-binding domain, and is analogous to previously documented BRAF fusions and splice variants known to reactivate RAS-RAF-MEK-ERK signaling...
November 24, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29164236/posttranscriptional-regulation-of-loxl1-expression-via-alternative-splicing-and-nonsense-mediated-mrna-decay-as-an-adaptive-stress-response
#19
Daniel Berner, Matthias Zenkel, Francesca Pasutto, Ursula Hoja, Panah Liravi, Gabriele C Gusek-Schneider, Friedrich E Kruse, Johannes Schödel, Andre Reis, Ursula Schlötzer-Schrehardt
Purpose: Alternative mRNA splicing coupled to nonsense-mediated decay (NMD) is a common mRNA surveillance pathway also known to dynamically modulate gene expression in response to cellular stress. Here, we investigated the involvement of this pathway in the regulation of lysyl oxidase-like 1 (LOXL1) expression in response to pseudoexfoliation (PEX)-associated pathophysiologic factors. Methods: Transcript levels of LOXL1 isoforms were determined in ocular tissues obtained from donor eyes without and with PEX syndrome...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29150940/tumor-suppressive-roles-of-%C3%AE-np63%C3%AE-mir-205-axis-in-epithelial-mesenchymal-transition-of-oral-squamous-cell-carcinoma-via-targeting-zeb1-and-zeb2
#20
Yuma Hashiguchi, Shintaro Kawano, Yuichi Goto, Kaori Yasuda, Naoki Kaneko, Taiki Sakamoto, Ryota Matsubara, Teppei Jinno, Yasuyuki Maruse, Hideaki Tanaka, Masahiko Morioka, Taichi Hattori, Shoichi Tanaka, Tamotsu Kiyoshima, Seiji Nakamura
We previously revealed that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63β, a splicing variant of ΔNp63, in oral squamous cell carcinoma (OSCC). Recent studies have highlighted the involvement of microRNA (miRNA) in EMT of cancer cells, though the mechanism remains unclear. To identify miRNAs responsible for ΔNp63β-mediated EMT, miRNA microarray analyses were performed by ΔNp63β-overexpression in OSCC cells; SQUU-B, which lacks ΔNp63 expression and displays EMT phenotypes. miRNAs microarray analyses revealed miR-205 was the most up-regulated following ΔNp63β-overexpression...
November 18, 2017: Journal of Cellular Physiology
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