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cancer splicing

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https://www.readbyqxmd.com/read/28717182/widespread-alternative-exon-usage-in-clinically-distinct-subtypes-of-invasive-ductal-carcinoma
#1
Sunniva Stordal Bjørklund, Anshuman Panda, Surendra Kumar, Michael Seiler, Doug Robinson, Jinesh Gheeya, Ming Yao, Grethe I Grenaker Alnæs, Deborah Toppmeyer, Margit Riis, Bjørn Naume, Anne-Lise Børresen-Dale, Vessela N Kristensen, Shridar Ganesan, Gyan Bhanot
Cancer cells can have different patterns of exon usage of individual genes when compared to normal tissue, suggesting that alternative splicing may play a role in shaping the tumor phenotype. The discovery and identification of gene variants has increased dramatically with the introduction of RNA-sequencing technology, which enables whole transcriptome analysis of known, as well as novel isoforms. Here we report alternative splicing and transcriptional events among subtypes of invasive ductal carcinoma in The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716814/potency-matched-dual-cytokine-antibody-fusion-proteins-for-cancer-therapy
#2
Roberto De Luca, Alex Soltermann, Francesca Pretto, Catherine Pemberton-Ross, Giovanni Pellegrini, Sarah Wulhfard, Dario Neri
A novel biopharmaceutical, consisting of the F8 monoclonal antibody (specific to a splice isoform of fibronectin) simultaneously fused to both tumor necrosis factor and interleukin-2, was found to react with the majority of solid tumors and hematological malignancies in mouse and man, but not with healthy adult tissues. The product selectively localized to neoplastic lesions in vivo, as evidenced by quantitative biodistribution studies using radioiodinated protein preparations. When the potency of the cytokine payloads was matched by a single-point mutation, the resulting fusion protein (IL2-F8-TNF(mut)) eradicated soft-tissue sarcomas in immunocompetent mice, which did not respond to individual antibody-cytokine fusion proteins or by standard doxorubicin treatment...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#3
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor receptor (EGFR) signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET co-receptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28716651/significance-of-a-to-i-rna-editing-of-transcripts-modulating-pharmacokinetics-and-pharmacodynamics
#4
REVIEW
Masataka Nakano, Miki Nakajima
RNA editing is a post-transcriptional process that alters the nucleotide sequence of RNA transcripts to generate transcriptome diversity. Among the various types of RNA editing, adenosine-to-inosine (A-to-I) RNA editing is the most frequent type of RNA editing in mammals. Adenosine deaminases acting on RNA (ADAR) enzymes, ADAR1 and ADAR2, convert adenosines in double-stranded RNA structures into inosines by hydrolytic deamination. Inosine forms a base pair with cytidine as if it were guanosine; therefore, the conversion may affect the amino acid sequence, splicing, microRNA targeting, and miRNA maturation...
July 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28716526/slc45a3-elk4-functions-as-a-long-non-coding-chimeric-rna
#5
Fujun Qin, Yanmei Zhang, Jia Liu, Hui Li
Gene fusions in cancer typically lead to the expression of a fusion protein or disrupt the expression of one of the parental genes. Here we report a new phenomenon whereby a fusion transcript functions as a long non-coding chimeric RNA (lnccRNA). This fusion RNA, SLC45A3-ELK4, generated by cis-splicing between neighboring genes, was found in prostate cancer. The fusion RNA encodes the same protein as ELK4. Intriguingly, we found that the fusion RNA level is less than 1% of wild type ELK4, unlikely to perturb the general pool of ELK4 protein...
July 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28707844/castration-resistance-prostate-cancer-what-is-in-the-pipeline
#6
Cosimo DE Nunzio, Fabrizio Presicce, Silvana Giacinti, Maria Bassanelli, Andrea Tubaro
INTRODUCTION: To evaluate the available evidence on the standard diagnosis and management of men with metastatic castration resistant prostate cancer (mCRPC), and providing the timely update on new pharmacological treatments. EVIDENCE ACQUISITION: A systematic literature search from from January 2000 until March 2017 was performed by combining the following MESH terms: castrate resistant prostate cancer, abiraterone, enzalutamide, 223radium, sipuleucel-T, docetaxel, cabazitaxel, resistance mechanisms, resistance to androgen deprivation, Androgen Receptor (AR) mutations, amplifications, splice variants, and AR alterations...
July 12, 2017: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/28707320/homology-model-of-the-human-trna-splicing-ligase-rtcb
#7
Argha Nandy, Patricia Saenz-Mendez, Adrienne M Gorman, Afshin Samali, Leif A Eriksson
RtcB is an essential human tRNA ligase required for ligating the 2',3'-cyclic phosphate and 5'-hydroxyl termini of cleaved tRNA halves during tRNA splicing and XBP1 fragments during endoplasmic reticulum stress. Activation of XBP1 has been implicated in various human tumors including breast cancer. Here we present, for the first time, a homology model of human RtcB (hRtcB) in complex with manganese and covalently bound GMP built from the Pyrococcus horikoshii RtcB (bRtcB) crystal structure, PDB ID 4DWQA. The structure is analyzed in terms of stereochemical quality, folding reliability, secondary structure similarity with bRtcB, druggability of the active site binding pocket and its metal-binding microenvironment...
July 13, 2017: Proteins
https://www.readbyqxmd.com/read/28706610/a-novel-variant-of-oct4-entitled-oct4b3-is-expressed-in-human-bladder-cancer-and-astrocytoma-cell-lines
#8
Ensieh M Poursani, Majid Mehravar, Bahram Mohammad Soltani, Seyed Javad Mowla, James E Trosko
BACKGROUND: Alternative splicing is an important mechanism that regulates gene expression and function in human cells. OCT4, a crucial pluripotency marker in embryonic stem/carcinoma cells generates several spliced variants in different cell types and cancers. The expression of OCT4 in cancers has been challenged in many studies. The existence of several OCT4 spliced variants and absence of specific discriminating primers is the main reason of this controversy. Therefore, using specific primers and discriminating OCT4 variants from each other might help to reduce these discrepancies in carcinogenesis and stem cell researches...
July 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28706133/serine-arginine-protein-kinase-1-srpk1-is-elevated-in-gastric-cancer-and-plays-oncogenic-functions
#9
Xiaotao Xu, Yuehua Wei, Shidong Wang, Man Luo, Heng Zeng
Serine-arginine protein kinase 1 (SRPK1) phosphorylates proteins involved in the regulation of several mRNA processing pathways including alternative splicing. SRPK1 has been reported to be over-expressed in multiple cancers including prostate, breast, lung and glioma. Several studies further identified that inhibition of SRPK1 showed tumor-suppressive effects, thus raising SRPK1 as a novel candidate chemotherapy target. Interestingly, SRPK1 plays tumor suppressing role in mouse embryonic fibroblasts, on that SRPK1-silencing induces cell transformation...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705809/the-oncogenic-role-of-the-spliced-somatostatin-receptor-sst5tmd4-variant-in-prostate-cancer
#10
Daniel Hormaechea-Agulla, Juan M Jiménez-Vacas, Enrique Gómez-Gómez, Fernando L López, Julia Carrasco-Valiente, José Valero-Rosa, María M Moreno, Rafael Sánchez-Sánchez, Rosa Ortega-Salas, Francisco Gracia-Navarro, Michael D Culler, Alejandro Ibáñez-Costa, Manuel D Gahete, María J Requena, Justo P Castaño, Raúl M Luque
sst5TMD4, a splice variant of the sst5 gene, is overexpressed and associated with aggressiveness in various endocrine-related tumors, but its presence, functional role, and mechanisms of actions in prostate cancer (PCa)-the most common cancer type in males-is completely unexplored. In this study, formalin-fixed, paraffin-embedded prostate pieces from patients with localized PCa, which included tumoral and nontumoral adjacent regions (n = 45), fresh biopsies from patients with high-risk PCa (n = 52), and healthy fresh prostates from cystoprostatectomies (n = 14) were examined...
July 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28705773/recent-progress-in-circular-rnas-in-human-cancers
#11
Guanqun Huang, Shuaihu Li, Nuo Yang, Yongdong Zou, Duo Zheng, Tian Xiao
Circular RNAs (circRNAs) are a large class of endogenous RNAs, formed by exon skipping or back-splicing events as covalently closed loops, which are expressed abundantly in mammalian cells. Although their biological functions remain largely unknown, recent studies show that circRNAs have three main functions in mammalian cells. First, circRNAs can regulate transcription and RNA splicing. Second, circRNAs function as microRNA (miRNA) sponges. Third, they can be translated into protein driven by N(6)-methyladenosine modification...
July 11, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28702748/-splice-variant-ar-v7-is-it-time-for-its-routine-use-as-a-predictive-marker-in-prostate-cancer
#12
REVIEW
I Tsaur, C Becker, P Thelen, F C Roos
Androgen receptor splice variants (AR-Vs), if overexpressed, lack the ligand-binding domain conveying metastasized castration-resistant prostate cancer with a therapeutic resistance to androgen receptor signaling inhibitors. Particularly AR-V7 has recently been proposed as a potential predictive biomarker to identify patients who would probably benefit most from taxane-based cytotoxic treatment. Several assays to substantiate or quantify AR-V7 expression have recently been proposed. However, their broad clinical value is still debatable...
July 12, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28698102/neonatal-nav1-5-protein-expression-in-normal-adult-human-tissues-and-breast-cancer
#13
Rezan Fahrioglu Yamaci, Scott P Fraser, Esra Battaloglu, Handan Kaya, Kamil Erguler, Christopher S Foster, Mustafa B A Djamgoz
Expression of the neonatal splice variant of the voltage-gated sodium channel α-subunit (VGSC) subtype Nav1.5 (nNav1.5), encoded by the gene SCN5A, was shown earlier to be upregulated in human breast cancer (BCa), both in vitro and in vivo. Channel activity promoted BCa invasion of Matrigel(®)in vitro and metastasis in vivo. Consequently, expression of nNav1.5 has been proposed as a functional biomarker of BCa cells with metastatic potential. Here, we have determined immunohistochemically both nNav1.5 and total VGSC (tVGSC) protein expression in a range of adult human tissues...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28694706/abnormalities-in-alternative-splicing-of-angiogenesis-related-genes-and-their-role-in-hiv-related-cancers
#14
REVIEW
Nonkululeko N Mthembu, Zukile Mbita, Rodney Hull, Zodwa Dlamini
Alternative splicing of mRNA leads to an increase in proteome biodiversity by allowing the generation of multiple mRNAs, coding for multiple protein isoforms of various structural and functional properties from a single primary pre-mRNA transcript. The protein isoforms produced are tightly regulated in normal development but are mostly deregulated in various cancers. In HIV-infected individuals with AIDS, there is an increase in aberrant alternative splicing, resulting in an increase in HIV/AIDS-related cancers, such as Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer...
2017: HIV/AIDS: Research and Palliative Care
https://www.readbyqxmd.com/read/28694503/cd44v8-10-as-a-potential-theranostic-biomarker-for-targeting-disseminated-cancer-cells-in-advanced-gastric-cancer
#15
Eun-Seok Choi, Hyunjin Kim, Hyung-Pyo Kim, Yongdoo Choi, Sung-Ho Goh
Gastric cancer is the third most common cause of cancer mortality, and the survival rate of stage IV advanced gastric cancer (AGC) patients with distant metastasis is very low. Thus, the detection and eradication of disseminated cancer cells by targeting cell surface molecules in AGC would improve patient survival. The hyaluronic acid receptor, CD44, has various isoforms generated by alternative splicing, and some isoforms are known to be correlated to gastric cancer. In this study, to find out the most appropriate CD44v for targeting AGC, we analysed the expression differences of CD44 isoforms at the mRNA level in stomach cancer cell lines as well as in 74 patients with AGC by using exon-specific qRT-PCR...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694326/genomic-analysis-of-220-ctcls-identifies-a-novel-recurrent-gain-of-function-alteration-in-rltpr-p-q575e
#16
Joonhee Park, Jingyi Yang, Alexander T Wenzel, Akshaya Ramachandran, Wung J Lee, Jay C Daniels, Juhyun Kim, Estela Martinez-Escala, Nduka Amankulor, Barbara Pro, Joan Guitart, Marc L Mendillo, Jeffrey N Savas, Titus J Boggon, Jaehyuk Choi
Cutaneous T cell lymphoma (CTCL) is an incurable non-Hodgkin lymphoma of the skin-homing T cell. In early stage disease, lesions are limited to the skin, but in later stage disease, the tumor cells can escape into the blood, the lymph nodes, and at times the visceral organs. To clarify the genomic basis of CTCL, we performed genomic analysis of 220 CTCLs. Our analyses identify 55 putative driver genes, including 17 genes not previously implicated in CTCL. These novel mutations are predicted to affect chromatin (BCOR, KDM6A, SMARCB1, TRRAP), immune surveillance (CD58, RFXAP), MAPK signaling (MAP2K1, NF1), NF-κB signaling (PRKCB, CSNK1A1), PI-3-Kinase signaling (PIK3R1, VAV1), RHOA/cytoskeleton remodeling (ARHGEF3), RNA-splicing (U2AF1), T cell receptor signaling (PTPRN2, RLTPR), and T cell differentiation (RARA)...
July 10, 2017: Blood
https://www.readbyqxmd.com/read/28693248/exon-7-splicing-variant-of-estrogen-receptor-%C3%AE-is-associated-with-pathological-invasiveness-in-smoking-independent-lung-adenocarcinoma
#17
Ayumi Suzuki, Katsuhiro Okuda, Motoki Yano, Risa Oda, Tadashi Sakane, Osamu Kawano, Hiroshi Haneda, Satoru Moriyama, Makoto Nakanishi, Ryoichi Nakanishi
Patients with smoking-independent lung cancer mainly consist of females, yet the molecular background of this epidemiological feature, other than epidermal growth factor receptor (EGFR) mutation, remains unclear. Several studies have revealed the association between female hormone-associated factors and the prognosis of lung cancer, however the data remain inconsistent. The present study focused on the expression of estrogen receptor (ER)α in order to elucidate this association in smoking-independent lung cancer...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28691182/hsp70-inhibitors-suppress-androgen-receptor-expression-in-lncap95-prostate-cancer-cells
#18
Kazuaki Kita, Masayuki Shiota, Masako Tanaka, Asuka Otsuka, Masaki Matsumoto, Minoru Kato, Satoshi Tamada, Hiroshi Iwao, Katsuyuki Miura, Tatsuya Nakatani, Shuhei Tomita
Androgen deprivation therapy (ADT) is initially effective for treating patients with advanced prostate cancer; however, the prostate cancer gradually becomes resistant to ADT, which is termed castration-resistant prostate cancer (CRPC). Androgen receptor splice variant 7 (AR-V7), one of the causes of CRPC, is correlated with the resistance to a new-generation AR antagonist (enzalutamide) and poor prognosis. Heat shock protein 70 (Hsp70) inhibitor is known to decrease the levels of full-length AR (AR-FL), but little is known about its effects against CRPC cells expressing AR-V7...
July 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/28685474/novel-brca1-splice-site-mutation-in-ovarian-cancer-patients-of-slavic-origin
#19
Ana Krivokuca, Vita Setrajcic Dragos, Ljiljana Stamatovic, Ana Blatnik, Ivana Boljevic, Vida Stegel, Jelena Rakobradovic, Petra Skerl, Stevo Jovandic, Mateja Krajc, Mirjana Brankovic Magic, Srdjan Novakovic
Mutations in breast cancer susceptibility gene 1 (BRCA1) lead to defects in a number of cellular pathways including DNA damage repair and transcriptional regulation, resulting in the elevated genome instability and predisposing to breast and ovarian cancers. We report a novel mutation LRG_292t1:c.4356delA,p.(Ala1453Glnfs*3) in the 12th exon of BRCA1, in the splice site region near the donor site of intron 12. It is a frameshift mutation with the termination codon generated on the third amino acid position from the site of deletion...
July 6, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28682884/microarray-expression-profile-of-circular-rnas-in-chronic-thromboembolic-pulmonary-hypertension
#20
Ran Miao, Ying Wang, Jun Wan, Dong Leng, Juanni Gong, Jifeng Li, Yan Liang, Zhenguo Zhai, Yuanhua Yang
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but debilitating and life-threatening complication of acute pulmonary embolism. Circular RNAs (circRNAs), presenting as covalently closed continuous loops, are RNA molecules with covalently joined 3'- and 5'-ends formed by back-splicing events. circRNAs may be significant biological molecules to understand disease mechanisms and to identify biomarkers for disease diagnosis and therapy. The aim of this study was to investigate the potential roles of circRNAs in CTEPH...
July 2017: Medicine (Baltimore)
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