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cancer splicing

Megan Cully
No abstract text is available yet for this article.
March 16, 2018: Nature Reviews. Drug Discovery
Yanchun Ma, Kun Chen, Zhenhua Yang, Ming Guan
Lung cancer is the most common type of malignancy to metastasize to the brain, with the median survival time of patients being 6-11 months. In the present study, the aim was to compare the actionable gene mutation profiles of primary lung adenocarcinoma (LC) samples and LC brain metastasis (LCBM) samples through targeted sequencing. Next generation sequencing (NGS) of 13 formalin-fixed, paraffin-embedded LC samples and 15 LCBM samples was performed using a customized OncoAim™ cancer panel and OncoAim™ RNA fusion panel on the MiSeq platform...
April 2018: Oncology Letters
J Hou, W Jiang, L Zhu, S Zhong, H Zhang, J Li, S Zhou, S Yang, Y He, D Wang, X Chen, F Deng, Q Zhang, J Wang, J Hu, W Zhang, L Ding, J Zhao, J Tang
Circular RNAs (CircRNAs) are a type of non-coding RNAs (NcRNAs) with a closed annular structure. Until next-generation sequencing (NGS) is developed, the misunderstanding of circRNAs 'splicing error' has changed, and the mysterious veil of circRNAs has been revealed. NGS provides an approach to investigate circRNAs. Many scholars point out that circRNAs may play an important role in many diseases, especially cancer. At the same time, exosomes, as a kind of extracellular vesicles loaded with many contents, are a hotspot in recent years...
March 13, 2018: Clinical & Translational Oncology
Hyoung Kyu Kim, Michael Huy Cuong Pham, Kyung Soo Ko, Byoung Doo Rhee, Jin Han
Alternative splicing (AS) of protein-coding messenger RNAs is an essential regulatory mechanism in eukaryotic gene expression that controls the proper function of proteins. It is also implicated in the physiological regulation of mitochondria and various ion channels. Considering that mis-splicing can result in various human diseases by modifying or abrogating important physiological protein functions, a fine-tuned balance of AS is essential for human health. Accumulated data highlight the importance of alternatively spliced isoforms in various diseases, including neurodegenerative disorders, cancer, immune and infectious diseases, cardiovascular diseases, and metabolic conditions...
March 13, 2018: Pflügers Archiv: European Journal of Physiology
Kun Qian, Hao Hu, Hui Xu, Y George Zheng
Protein arginine methyltransferases (PRMTs) are crucial epigenetic regulators in eukaryotic organisms that serve as histone writers for chromatin remodeling. PRMTs also methylate a variety of non-histone protein substrates to modulate their function and activity. The development of potent PRMT inhibitors has become an emerging and imperative research area in the drug discovery field to provide novel therapeutic agents for treating diseases and as tools to investigate the biological functions of PRMTs. PRMT1 is the major type I enzyme that catalyzes the formation of asymmetric dimethyl arginine, and PRMT1 plays important regulatory roles in signal transduction, transcriptional activation, RNA splicing, and DNA repair...
2018: Signal Transduction and Targeted Therapy
Paramita Saha, Kasturi Datta
Cancer is a complex, multi-factorial, multi-stage disease and a global threat to human health. Early detection of nature and stage of cancer is highly crucial for disease management. Recent studies have proved beyond any doubt about the involvement of the ubiquitous, myriad ligand binding, multi-functional human protein, hyaluronan-binding protein 1 (HABP1), which is identical to the splicing factor associated protein (p32) and the receptor of the globular head of the complement component (gC1qR) in tumorigenesis and cancer metastasis...
February 13, 2018: Oncotarget
Ryuji Yamamoto, Tsuyoshi Osawa, Yusuke Sasaki, Shogo Yamamoto, Motonobu Anai, Kouji Izumi, Yoshihiro Matsumura, Juro Sakai, Hiroyuki Aburatani, Atsushi Mizokami, Tatsuhiko Kodama, Toshiya Tanaka
The non-POU domain-containing octamer binding protein p54nrb /NONO is a multifunctional nuclear protein involved in RNA splicing, processing, and transcriptional regulation of nuclear hormone receptors. Through chromosome copy number analysis via whole-exome sequencing, we revealed amplification of the chromosome Xq11.22-q21.33 locus containing the androgen receptor ( AR ) and NONO genes in androgen-independent, castration-resistant prostate cancer (CRPC)-like LNCaP-SF cells. Moreover, NONO was frequently amplified and overexpressed in patients with CRPC...
February 13, 2018: Oncotarget
Prema S Rao, Ryan Endicott, Randy Mullins, U Subrahmanyeswara Rao
Comparison of human genome sequences from different individuals has unraveled that genes involved in the drug efficacy and metabolism are polymorphic, harboring mutations, splicing variations and other alterations. These data provide a reasonable explanation for the inter-individual variations observed in drug therapy. Thus, a detailed molecular analysis and an in-depth knowledge of these genes is a prerequisite to practice pharmacogenomics-based medicine. We have introduced a 6-week laboratory research rotation to train students in the expression analysis of different pharmacogenes combined with bioinformatics tools...
March 8, 2018: Pharmacogenomics Journal
Giorgio Giurato, Giovanni Nassa, Annamaria Salvati, Elena Alexandrova, Francesca Rizzo, Tuula A Nyman, Alessandro Weisz, Roberta Tarallo
The nuclear receptor estrogen receptor 2 (ESR2, ERβ) modulates cancer cell proliferation and tumor growth, exerting an oncosuppressive role in breast cancer (BC). Interaction proteomics by tandem affinity purification coupled to mass spectrometry was previously applied in BC cells to identify proteins acting in concert with ERβ to control key cellular functions, including gene transcription, RNA splicing and post-transcriptional mRNA regulation. These studies revealed an involvement of RNA in ERβ interactome assembly and functions...
March 6, 2018: Scientific Data
Takatsugu Okegawa, Naoki Ninomiya, Kazuki Masuda, Yu Nakamura, Mitsuhiro Tambo, Kikuo Nutahara
OBJECTIVE: We examined whether androgen receptor splice variant 7 (AR-V7) in circulating tumor cell(CTC)clusters can be used to predict survival in patients with bone metastatic castration resistant-prostate cancer (mCRPC) treated with abiraterone or enzalutamide. METHODS: We retrospectively enrolled 98 patients with CRPC on abiraterone or enzalutamide, and investigated the prognostic value of CTC cluster detection (+ v -) and AR-V7 detection (+ v -) using a CTC cluster detection - based AR-V7 mRNA assay...
March 5, 2018: Prostate
Christy L Rhine, Kamil J Cygan, Rachel Soemedi, Samantha Maguire, Michael F Murray, Sean F Monaghan, William G Fairbrother
Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5' and 3' splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77%) of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene...
March 5, 2018: PLoS Genetics
Li Wang, John A Wrobel, Ling Xie, DongXu Li, Giada Zurlo, Huali Shen, Pengyuan Yang, Zefeng Wang, Yibing Peng, Harsha P Gunawardena, Qing Zhang, Xian Chen
To discriminate the patient subpopulations with different clinical outcomes within each breast cancer (BC) subtype, we introduce a robust, clinical-practical, activity-based proteogenomic method that identifies, in their oncogenically active states, candidate biomarker genes bearing patient-specific transcriptomic/genomic alterations of prognostic value. First, we used the intronic splicing enhancer (ISE) probes to sort ISE-interacting trans-acting protein factors (trans-interactome) directly from a tumor tissue for subsequent mass spectrometry characterization...
February 27, 2018: Cell Chemical Biology
Ellen Heitzer, Michael R Speicher
<b/> In this issue of Cancer Discovery , Miyamoto and colleagues adapted their microfluidic CTC-iChip isolation platform with a digital RNA-PCR readout for eight prostate-specific transcripts and two assays for the androgen receptor mRNA splice variant ARV7 and the TMPRSS2-ERG translocation transcript. In patients with metastatic castrate-resistant prostate cancer at initiating abiraterone therapy in a first-line setting, the resulting RNA-based digital circulating tumor cell signatures identified patients with a shorter overall survival, and in patients with clinically localized disease, the signatures identified those with seminal vesicle invasion and pelvic lymph node involvement...
March 2018: Cancer Discovery
Ye Tao, Neil Gross, Xiaojiao Fan, Jianming Yang, Maikun Teng, Xu Li, Guojun Li, Yang Zhang, Zhigang Huang
BACKGROUND: As hybrid RNAs, transcription-induced chimeras (TICs) may have tumor-promoting properties, and some specific chimeras have become important diagnostic markers and therapeutic targets for cancer. METHODS: We examined 23 paired laryngeal cancer (LC) tissues and adjacent normal mucous membrane tissue samples (ANMMTs). Three of these pairs were used for comparative transcriptomic analysis using high-throughput sequencing. Furthermore, we used real-time polymerase chain reaction (RT-PCR) for further validation in 20 samples...
March 2, 2018: BMC Cancer
Yusuke Ito, Marianne D Sadar
Enzalutamide is a nonsteroidal antiandrogen for the treatment of metastatic castration-resistant prostate cancer (mCRPC) both before and after chemotherapy. Enzalutamide is more effective than its predecessor bicalutamide, which was analyzed in head-to-head studies of patients with CRPC. This family of nonsteroidal antiandrogens is now comprised of four drugs approved by the US Food and Drug Administration with two investigational drugs in clinical trials. Antiandrogens have been employed clinically for more than five decades to provide a rich resource of information...
2018: Research and Reports in Urology
Lea Weber, Désirée Maßberg, Christian Becker, Janine Altmüller, Burkhard Ubrig, Gabriele Bonatz, Gerhard Wölk, Stathis Philippou, Andrea Tannapfel, Hanns Hatt, Günter Gisselmann
Olfactory receptors (ORs) are known to be expressed in a variety of human tissues and act on different physiological processes, such as cell migration, proliferation, or secretion and have been found to function as biomarkers for carcinoma tissues of prostate, lung, and small intestine. In this study, we analyzed the OR expression profiles of several different carcinoma tissues, with a focus on breast cancer. The expression of OR2B6 was detectable in breast carcinoma tissues; here, transcripts of OR2B6 were detected in 73% of all breast carcinoma cell lines and in over 80% of all of the breast carcinoma tissues analyzed...
2018: Frontiers in Oncology
Lorenzo I Finci, Xiaofeng Zhang, Xiuliang Huang, Qiang Zhou, Jennifer Tsai, Teng Teng, Anant Agrawal, Betty Chan, Sean Irwin, Craig Karr, Andrew Cook, Ping Zhu, Dominic Reynolds, Peter G Smith, Peter Fekkes, Silvia Buonamici, Nicholas A Larsen
Somatic mutations in spliceosome proteins lead to dysregulated RNA splicing and are observed in a variety of cancers. These genetic aberrations may offer a potential intervention point for targeted therapeutics. SF3B1, part of the U2 small nuclear RNP (snRNP), is targeted by splicing modulators, including E7107, the first to enter clinical trials, and, more recently, H3B-8800. Modulating splicing represents a first-in-class opportunity in drug discovery, and elucidating the structural basis for the mode of action opens up new possibilities for structure-based drug design...
February 1, 2018: Genes & Development
Rezvan Esmaeili, Nasrin Abdoli, Fatemeh Yadegari, Mohamadreza Neishaboury, Leila Farahmand, Ahmad Kaviani, Keivan Majidzadeh-A
Background: CD44 encoded by a single gene is a cell surface transmembrane glycoprotein. Exon 2 is one of the important exons to bind CD44 protein to hyaluronan. Experimental evidences show that hyaluronan-CD44 interaction intensifies the proliferation, migration, and invasion of breast cancer cells. Therefore, the current study aimed at investigating the association between specific polymorphisms in exon 2 and its flanking region of CD44 with predisposition to breast cancer. Methods: In the current study, 175 Iranian female patients with breast cancer and 175 age-matched healthy controls were recruited in biobank, Breast Cancer Research Center, Tehran, Iran...
2018: Cancer Cell International
Marie Joncquel-Chevalier Curt, Marie-Adélaïde Bout, Monique Fontaine, Isabelle Kim, Guillemette Huet, Soumeya Bekri, Gilles Morin, Stéphanie Moortgat, Alexandre Moerman, Jean-Marie Cuisset, David Cheillan, Joseph Vamecq
Creatine transporter is currently the focus of renewed interest with emerging roles in brain neurotransmission and physiology, and the bioenergetics of cancer metastases. We here report on amendments of a standard creatine uptake assay which might help clinical chemistry laboratories to extend their current range of measurements of creatine and metabolites in body fluids to functional enzyme explorations. In this respect, short incubation times and the use of a stable-isotope-labeled substrate (D3 -creatine) preceded by a creatine wash-out step from cultured fibroblast cells by removal of fetal bovine serum (rich in creatine) from the incubation medium are recommended...
February 16, 2018: Molecular Genetics and Metabolism
Padmanaban S Suresh, Rie Tsutsumi, Thejaswini Venkatesh
YBX1 (Y box binding protein 1) is an RNA-/DNA-binding multifunctional protein harboring the classical cold shock protein (CSD) domain, an A/P domain, and a long C-terminal domain with alternating positively and negatively charged amino acids. It is a well-established oncogenic transcriptional factor, and regulates apoptosis, translation, cell proliferation, mRNA splicing, repair, differentiation, and stress response. The non-coding transcriptome has added yet another layer of complexity to the YBX1-mediated master regulation of cellular functions...
February 19, 2018: European Journal of Cell Biology
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