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RNA sequencing Cancer

Junxiong Cheng, Dan Guo, Xi Chen, Ting Wang, Jiayi Huang
Objective To construct a recombinant adenovirus expressing siRNA targeting human sclerostin (SOST) gene, and test the function of MG-63 cells while co-cultured with MDA-MB-231 cells infected by Ad-siSOST. MethodsAccording to the RNA sequence of SOST gene, two pairs of primers which contained 3 siRNA sequences were designed, and a pB2B plasmid was taken as template to amplify 2 DNA sequences. Both of the 2 DNA sequences were ligated to pAdTrace-OK by Gibson DNA Assembly way. After homologous recombination between recombinant shuttle plasmid and adenovirus vector plasmid, the adenovirus was packaged in HEK-293 cells...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Yan Guo, Jie Wu, Shilin Zhao, Fei Ye, Yinghao Su, Travis Clark, Quanhu Sheng, Brian Lehmann, Xiao-Ou Shu, Qiuyin Cai
Background. Proper rRNA depletion is crucial for the successful utilization of FFPE specimens when studying gene expression. We performed a study to evaluate two major rRNA depletion methods: Ribo-Zero and RNase H. RNAs extracted from 4 samples were treated with the two rRNA depletion methods in duplicate and sequenced (N = 16). We evaluated their reducibility, ability to detect RNA, and ability to molecularly subtype these triple negative breast cancer specimens. Results. Both rRNA depletion methods produced consistent data between the technical replicates...
2016: International Journal of Genomics
S Manier, J T Powers, A Sacco, S V Glavey, D Huynh, M R Reagan, K Z Salem, M Moschetta, J Shi, Y Mishima, C Roche-Lestienne, X Leleu, A M Roccaro, G Q Daley, I M Ghobrial
MYC is a major oncogenic driver of Multiple Myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM...
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Xiaosheng He, Xutao Lin, Muyan Cai, Dejun Fan, Xiuting Chen, Lei Wang, Xiaojian Wu, Ping Lan, Jianping Wang
Cytoplasmic polyadenylation element-binding protein 4 (CPEB4), a zinc-finger-containing sequence-specific RNA-binding protein, has been associated with tumor proliferation, invasion, and migration. Expression of CPEB4 and its prognostic significance in human colorectal cancer (CRC) have not been studied. The aim of the present study was to investigate expression of CPEB4 and its prognostic significance in CRC. Expression of CPEB4 in CRC tissues from two independent cohorts was examined by immunohistochemistry...
October 22, 2016: Virchows Archiv: An International Journal of Pathology
Maoqi Xu, Liang Chen
The individual sample heterogeneity is one of the biggest obstacles in biomarker identification for complex diseases such as cancers. Current statistical models to identify differentially expressed genes between disease and control groups often overlook the substantial human sample heterogeneity. Meanwhile, traditional nonparametric tests lose detailed data information and sacrifice the analysis power, although they are distribution free and robust to heterogeneity. Here, we propose an empirical likelihood ratio test with a mean-variance relationship constraint (ELTSeq) for the differential expression analysis of RNA sequencing (RNA-seq)...
October 21, 2016: Briefings in Bioinformatics
Binyi Lin, Tianchi Chen, Qijun Zhang, Xiaoxiao Lu, Zhiyun Zheng, Jun Ding, Jinfeng Liu, Zhe Yang, Lei Geng, Liming Wu, Lin Zhou, Shusen Zheng
To investigate the potential oncogene promoting recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT), throughput RNA sequencing was performed in a subgroup of HCC patients. The up-regulated FAM83D in HCC tissues was found and further verified in 150 patients by real-time PCR and immunohistochemistry. FAM83D overexpression significantly correlated with high HCC recurrence rate following LT and poor HCC characteristics such as high AFP, poor differentiation. Of cancer stem cells (CSCs) markers, CD44 expression was effectively suppressed when FAM83D was knocked down by siRNA...
October 18, 2016: Oncotarget
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
Sundhar Ramalingam, Adva Eisenberg, Wen Chi Foo, Jennifer Freedman, Andrew J Armstrong, Larry G Moss, Michael R Harrison
Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome...
October 21, 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
Chao Shang, Yan Guo, Yang Hong, Yi-Xue Xue
Tumour suppressor candidate 7 (TUSC7) is a novel tumor suppressor gene generating long non-coding RNA (lncRNAs) in several types of human cancers. The expression and function of TUSC7 in human brain glioma has yet to be elucidated. In this study, TUSC7 was poorly expressed in tissues and cell lines of glioma, and the lower expression was correlated with glioma of the worse histological grade. Moreover, TUSC7 is a prognostic biomarker of glioma patients. Up-regulation of TUSC7 suppressed cellular proliferation and invasion of glioma cells, and accelerated cellular apoptosis...
2016: Frontiers in Cellular Neuroscience
Wayne O Miles, Antonio Lembo, Angela Volorio, Elena Brachtel, Bin Tian, Dennis Sgroi, Paolo Provero, Nicholas Dyson
Alternative polyadenylation (APA) is a process that changes the post-transcriptional regulation and translation potential of mRNAs via addition or deletion of 3'UTR sequences. To identify post-transcriptional regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3'UTR region found that APA-mediated removal of Pumilio Regulatory Elements (PRE) was unusually common. Breast tumor sub-type specific APA profiling identified triple-negative breast tumors as having the highest levels of APA...
October 10, 2016: Cancer Research
Qiangfeng Wang, Huanxia Yang, Lingjiao Wu, Jian Yao, Xiaohua Meng, Han Jiang, Cheng Xiao, Fusheng Wu
BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) have been shown to play a critical regulatory role in cancer biology. However, the contribution of lncRNAs to papillary thyroid cancer (PTC) remains largely unknown. METHODS: RNA sequencing and quantitative reverse transcription PCR (qRT-PCR) were used to detect and verify, respectively, changes to the transcriptomic profile in 12 PTC tissues compared to paired normal adjacent tissues. The statistical correlation between differentially expressed lncRNAs and clinicopathological characteristics was analysed, and potential lncRNA functions were predicted by examining annotations for the co-expressed mRNAs...
October 19, 2016: Thyroid: Official Journal of the American Thyroid Association
Iris J H van Vlodrop, Sophie C Joosten, Tim de Meyer, Kim M Smits, Leander Van Neste, Veerle Melotte, Marcella Baldewijns, Leo J Schouten, Piet A van den Brandt, Jana Jeschke, Joo Mi Yi, Kornel Schuebel, Nita Ahuja, James G Herman, Maureen Aarts, Fred T Bosman, Wim Van Criekinge, Manon van Engeland
PURPOSE: The currently used prognostic models for patients with non-metastatic clear cell renal cell carcinoma (ccRCC) are based on clinicopathological features and might be improved by adding molecular markers. Epigenetic alterations occur frequently in ccRCC and are promising biomarkers. The aim of this study is to identify prognostic promoter methylation markers for ccRCC. EXPERIMENTAL DESIGN: We integrated data generated by massive parallel sequencing of methyl-binding domain enriched DNA and microarray based RNA expression profiling of 5-aza-2'-deoxycytidine treated ccRCC cell lines to comprehensively characterize the ccRCC methylome...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sofia Lisanti, David S Garlick, Kelly G Bryant, Michele Tavecchio, Gordon B Mills, Yiling Lu, Andrew V Kossenkov, Louise C Showe, Lucia R Languino, Dario C Altieri
Protein homeostasis, or proteostasis is required for mitochondrial function, but its role in cancer is controversial. Here, we show that transgenic mice expressing the mitochondrial chaperone, TRAP1 in the prostate develop epithelial hyperplasia and cellular atypia. When examined on a Pten+/- background, a common alteration in human prostate cancer, TRAP1 transgenic mice showed accelerated incidence of invasive prostatic adenocarcinoma, characterized by increased cell proliferation and reduced apoptosis, in situ...
October 17, 2016: Journal of Biological Chemistry
Pravin Kumar Ankush Jagtap, Divita Garg, Tobias G Kapp, Cindy L Will, Oliver Demmer, Reinhard Luhrmann, Horst Kessler, Michael Sattler
U2AF homology motifs (UHMs) are atypical RNA Recognition Motif (RRM) domains that mediate critical protein-protein interactions during the regulation of alternative pre-mRNA splicing and other processes. The recognition of UHM domains by UHM Ligand Motif (ULM) peptide sequences plays important roles during early steps of spliceosome assembly. Splicing factor 45 kDa (SPF45) is an alternative splicing factor implicated in breast and lung cancer and splicing regulation of apoptosis-linked pre-mRNAs by SPF45 was shown to depend on interactions of its UHM domain with ULM motifs in constitutive splicing factors...
October 18, 2016: Journal of Medicinal Chemistry
O Sakiragaoglu, A L Munn
To inhibit telomerase activity, a construct which contains artificial introns in the enhanced green fluorescent protein (EGFP) gene that encodes small hairpin RNA (shRNA) sequences that target human telomerase reverse transcriptase (hTERT) gene expression was designed and tested for its effect on lung cancer cell line. On intron splicing from the construct, intronic sequences were released and formed shRNA in the cells. After transfection of the construct, hTERT mRNA expression decreased by approximately 55 % in A549 cells...
October 17, 2016: Molecular Biotechnology
Philip H Abbosh, Jonathan E Rosenberg, Elizabeth R Plimack
There are very few biomarkers used to diagnose bladder cancer and no clinically approved biomarkers for prediction or prognostication of this disease. All currently available biomarkers are based on urine tests, and thus, they may not be applicable to patients with extravesical tumors. Biopsy of metastatic sites requires an invasive procedure, whereas serum-based markers, which can be easily obtained and serially measured, thus have obvious merit. These deficiencies may be overcome with advances in genome sequencing, identification of circulating tumor cells, and RNA-, protein-, and DNA-based biomarkers...
October 14, 2016: Urologic Oncology
Michele Balsamo, Chandrani Mondal, Guillaume Carmona, Leslie M McClain, Daisy N Riquelme, Jenny Tadros, Duan Ma, Eliza Vasile, John S Condeelis, Douglas A Lauffenburger, Frank B Gertler
During tumor progression, alternative splicing gives rise to different Mena protein isoforms. We analyzed how Mena11a, an isoform enriched in epithelia and epithelial-like cells, affects Mena-dependent regulation of actin dynamics and cell behavior. While other Mena isoforms promote actin polymerization and drive membrane protrusion, we find that Mena11a decreases actin polymerization and growth factor-stimulated membrane protrusion at lamellipodia. Ectopic Mena11a expression slows mesenchymal-like cell motility, while isoform-specific depletion of endogenous Mena11a in epithelial-like tumor cells perturbs cell:cell junctions and increases membrane protrusion and overall cell motility...
October 17, 2016: Scientific Reports
Xiaozhou Fan, Alexander V Alekseyenko, Jing Wu, Brandilyn A Peters, Eric J Jacobs, Susan M Gapstur, Mark P Purdue, Christian C Abnet, Rachael Stolzenberg-Solomon, George Miller, Jacques Ravel, Richard B Hayes, Jiyoung Ahn
OBJECTIVE: A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study. DESIGN: We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial...
October 14, 2016: Gut
Mayuko Furuta, Masaki Ueno, Akihiro Fujimoto, Shinya Hayami, Satoru Yasukawa, Fumiyoshi Kojima, Koji Arihiro, Yoshiiku Kawakami, Christopher P Wardell, Yuichi Shiraishi, Hiroko Tanaka, Kaoru Nakano, Kazuhiro Maejima, Aya Sasaki-Oku, Naoki Tokunaga, Keith A Boroevich, Tetsuo Abe, Hiroshi Aikata, Hideki Ohdan, Kunihito Goto, Michiaki Kubo, Tatsuhiko Tsunoda, Satoru Miyano, Kazuaki Chayama, Hiroki Yamaue, Hidewaki Nakagawa
BACKGROUND & AIMS: Liver cancer has a high risk of multi-centric (MC) occurrence due to a strong carcinogenic background in the liver, in addition to a high risk of intrahepatic metastasis (IM). There are large characteristic differences between IM and MC with regards to their development and clinical outcome, but discriminating between IM and MC is usually non-trivial with respect to clinical or pathological aspects. METHODS: In this study, we performed whole-genome and RNA sequencing analyses of 49 liver nodules and two extra-hepatic metastatic tumors from 23 patients to investigate for any potential to discriminate between IM and MC at the molecular level...
October 11, 2016: Journal of Hepatology
Shreyas Shah, Kiran Jadhav, Vandana Shah, Nidhi Gupta, Kapil Dagrus
: The vast majority of cancer epigenetic research is now focused on micro RNA (miRNA). Though thousands of miRNA have been identified, the validation of their role is a continuous process. AIM: the aim of this paper is to comprehensively review the role of miRNA 21 in Oral cancer as a marker for diagnosis, prognosis and therapeutic target. METHOD: The data was collected from major search engines like PubMed, Science Direct, Cochrane library and Google Patents with the key words miRNA 21, miRNA and Oral Cancer, miRNA 21 prognostic role, miRNA therapeutic target etc...
September 19, 2016: MicroRNA
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