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RNA sequencing Breast Cancer

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https://www.readbyqxmd.com/read/27901097/sequencing-based-breast-cancer-diagnostics-as-an-alternative-to-routine-biomarkers
#1
Mattias Rantalainen, Daniel Klevebring, Johan Lindberg, Emma Ivansson, Gustaf Rosin, Lorand Kis, Fuat Celebioglu, Irma Fredriksson, Kamila Czene, Jan Frisell, Johan Hartman, Jonas Bergh, Henrik Grönberg
Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900322/patterns-of-transposable-element-expression-and-insertion-in-cancer
#2
Evan A Clayton, Lu Wang, Lavanya Rishishwar, Jianrong Wang, John F McDonald, I King Jordan
Human transposable element (TE) activity in somatic tissues causes mutations that can contribute to tumorigenesis. Indeed, TE insertion mutations have been implicated in the etiology of a number of different cancer types. Nevertheless, the full extent of somatic TE activity, along with its relationship to tumorigenesis, have yet to be fully explored. Recent developments in bioinformatics software make it possible to analyze TE expression levels and TE insertional activity directly from transcriptome (RNA-seq) and whole genome (DNA-seq) next-generation sequence data...
2016: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/27899656/idp-ase-haplotyping-and-quantifying-allele-specific-expression-at-the-gene-and-gene-isoform-level-by-hybrid-sequencing
#3
Benjamin Deonovic, Yunhao Wang, Jason Weirather, Xiu-Jie Wang, Kin Fai Au
Allele-specific expression (ASE) is a fundamental problem in studying gene regulation and diploid transcriptome profiles, with two key challenges: (i) haplotyping and (ii) estimation of ASE at the gene isoform level. Existing ASE analysis methods are limited by a dependence on haplotyping from laborious experiments or extra genome/family trio data. In addition, there is a lack of methods for gene isoform level ASE analysis. We developed a tool, IDP-ASE, for full ASE analysis. By innovative integration of Third Generation Sequencing (TGS) long reads with Second Generation Sequencing (SGS) short reads, the accuracy of haplotyping and ASE quantification at the gene and gene isoform level was greatly improved as demonstrated by the gold standard data GM12878 data and semi-simulation data...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895496/identification-of-lncrna-fam83h-as1-as-a-novel-prognostic-marker-in-luminal-subtype-breast-cancer
#4
Fan Yang, Shi-Xu Lv, Lin Lv, Ye-Huan Liu, Si-Yang Dong, Zhi-Han Yao, Xuan-Xuan Dai, Xiao-Hua Zhang, Ou-Chen Wang
BACKGROUND: Luminal subtype breast cancer accounts for a predominant number of breast cancers. Considering the heterogeneity of the disease, it is urgent to develop novel biomarkers to improve risk stratification and optimize therapy choices. Long non-coding RNA (lncRNA) represents an emerging and understudied class of transcripts that play a significant role in cancer biology. Growing knowledge of cancer-associated lncRNAs contributes to the development of molecular markers for prognosis evaluation and gene therapy...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27888420/endocan-as-a-prognostic-biomarker-of-triple-negative-breast-cancer
#5
Atsunobu Sagara, Katsuhide Igarashi, Maky Otsuka, Akihiro Kodama, Mutsumi Yamashita, Rei Sugiura, Takeshi Karasawa, Kazuhiko Arakawa, Michiko Narita, Naoko Kuzumaki, Minoru Narita, Yoshinori Kato
PURPOSE: Triple-negative breast cancer (TNBC) has aggressive characteristics and fewer treatment options than other subtypes. The purpose of this study was to explore prognostic biomarkers for TNBC that can be easily detected from the blood samples. METHODS: MDA-MB-231 and MDA-MB-231BR, a brain metastatic variant of the human TNBC cell line MDA-MB-231, were used as less and more aggressive models of TNBC, respectively. The extent to which the candidate gene/protein identified by RNA sequencing correlated well with aggressiveness of TNBC and how much protein was detected from the blood of tumor-bearing mice were evaluated...
November 25, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27879434/5-terminal-nucleotide-variations-in-human-cytoplasmic-trnahisgug-and-its-5-halves
#6
Megumi Shigematsu, Yohei Kirino
Transfer RNAs (tRNAs) are fundamental adapter components of translational machinery. tRNAs can further serve as a source of tRNA-derived non-coding RNAs that play important roles in various biological processes beyond translation. Among all species of tRNAs, tRNAHisGUG has been known to uniquely contain an additional guanosine residue at the -1 position (G-1) of its 5'-end. To analyze this -1 nucleotide in detail, we developed a TaqMan qRT-PCR method which can distinctively quantify human mature cytoplasmic tRNAHisGUG containing G-1, U-1, A-1, or C-1 or lacking the -1 nucleotide (starting from G1)...
November 22, 2016: RNA
https://www.readbyqxmd.com/read/27874091/hmga1p7-pseudogene-regulates-h19-and-igf2-expression-by-a-competitive-endogenous-rna-mechanism
#7
Marco De Martino, Floriana Forzati, Marianna Marfella, Simona Pellecchia, Claudio Arra, Luigi Terracciano, Alfredo Fusco, Francesco Esposito
Recent studies have revealed that pseudogene transcripts can function as competing endogenous RNAs, and thereby can also contribute to cancer when dysregulated. We have recently identified two pseudogenes, HMGA1P6 and HMGA1P7 for the HMGA1 gene whose overexpression has a critical role in cancer progression. These pseudogenes work as competitive endogenous RNA decoys for HMGA1 and other cancer related genes suggesting their role in carcinogenesis. Looking for new HMGA1 pseudogene ceRNAs, we performed RNA sequencing technology on mouse embryonic fibroblasts deriving from transgenic mice overexpressing HMGA1P7...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27858503/high-throughput-sequencing-of-two-populations-of-extracellular-vesicles-provides-an-mrna-signature-that-can-be-detected-in-the-circulation-of-breast-cancer-patients
#8
Andrew Conley, Valentina R Minciacchi, Dhong Hyun Lee, Beatrice S Knudsen, Beth Y Karlan, Luigi Citrigno, Giuseppe Viglietto, Muneesh Tewari, Michael R Freeman, Francesca Demichelis, Dolores Di Vizio
Extracellular vesicles (EVs) contain a wide range of RNA types with a reported prevalence of non-coding RNA. To date a comprehensive characterization of the protein coding transcripts in EVs is still lacking. We performed RNA-Sequencing (RNA-Seq) of two EV populations and identified a small fraction of transcripts that were expressed at significantly different levels in large oncosomes and exosomes, suggesting they may mediate specialized functions. However, these two EV populations exhibited a common mRNA signature that, in comparison to their donor cells, was significantly enriched in mRNAs encoding E2F transcriptional targets and histone proteins...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27855392/the-emerging-roles-of-long-noncoding-rna-ror-lincrna-ror-and-its-possible-mechanisms-in-human-cancers
#9
Yan Pan, Chen Li, Jing Chen, Kai Zhang, Xiaoyuan Chu, Rui Wang, Longbang Chen
To date, there is only up to 2% of protein-coding genes that are stably transcribed, whereas the vast majority are non-coding RNAs (ncRNAs). These ncRNAs, also known as non-messenger RNAs (nmRNAs) or functional RNAs (fRNAs), include transfer RNAs, ribosomal RNAs, microRNAs and long non-coding RNAs (lncRNAs). With the advance of high-resolution microarrays and massively parallel sequencing technology, lncRNAs have gained extended attentions nowadays and are found to play important roles in tumorigenesis and progression of human cancers...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27853307/intronless-wnt10b-short-variant-underlies-new-recurrent-allele-specific-rearrangement-in-acute-myeloid-leukaemia
#10
Francesca Lazzaroni, Luca Del Giacco, Daniele Biasci, Mauro Turrini, Laura Prosperi, Roberto Brusamolino, Roberto Cairoli, Alessandro Beghini
Defects in the control of Wnt signaling have emerged as a recurrent mechanism involved in cancer pathogenesis and acute myeloid leukaemia (AML), including the hematopoietic regeneration-associated WNT10B in AC133(bright) leukaemia cells, although the existence of a specific mechanism remains unproven. We have obtained evidences for a recurrent rearrangement, which involved the WNT10B locus (WNT10B(R)) within intron 1 (IVS1) and flanked at the 5' by non-human sequences whose origin remains to be elucidated; it also expressed a transcript variant (WNT10B(IVS1)) which was mainly detected in a cohort of patients with intermediate/unfavorable risk AML...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27832764/blood-mirnomes-and-transcriptomes-reveal-novel-longevity-mechanisms-in-the-long-lived-bat-myotis-myotis
#11
Zixia Huang, David Jebb, Emma C Teeling
BACKGROUND: Chiroptera, the bats, are the only order of mammals capable of true self-powered flight. Bats exhibit a number of other exceptional traits such as echolocation, viral tolerance and, perhaps most puzzlingly, extreme longevity given their body size. Little is known about the molecular mechanisms driving their extended longevity particularly at the levels of gene expression and post-transcriptional regulation. To elucidate the molecular mechanisms that may underlie their unusual longevity, we have deep sequenced 246...
November 10, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27829357/systematic-identification-of-ctr9-regulome-in-er%C3%AE-positive-breast-cancer
#12
Hao Zeng, Li Lu, Ngai Ting Chan, Mark Horswill, Paul Ahlquist, Xuehua Zhong, Wei Xu
BACKGROUND: We had previously identified Ctr9, the key scaffold subunit of the human RNA polymerase II (RNAPII) associated factor complex (PAFc), as a key factor regulating a massive ERα target gene expression and ERα-positive breast cancer growth. Furthermore, we have shown that knockdown of Ctr9 reduces ERα protein stability and decreases the occupancy of ERα and RNAPII at a few ERα-target loci. However, it remains to be determined whether Ctr9 controls ERα-target gene expression by regulating the global chromatin occupancy of ERα and RNAPII in the presence of estrogen...
November 9, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27829232/circular-rnas-and-their-associations-with-breast-cancer-subtypes
#13
Asha A Nair, Nifang Niu, Xiaojia Tang, Kevin J Thompson, Liewei Wang, Jean-Pierre Kocher, Subbaya Subramanian, Krishna R Kalari
Circular RNAs (circRNAs) are highly stable forms of non-coding RNAs with diverse biological functions. They are implicated in modulation of gene expression thus affecting various cellular and disease processes. Based on existing bioinformatics approaches, we developed a comprehensive workflow called Circ-Seq to identify and report expressed circRNAs. Circ-Seq also provides informative genomic annotation along circRNA fused junctions thus allowing prioritization of circRNA candidates. We applied Circ-Seq first to RNA-sequence data from breast cancer cell lines and validated one of the large circRNAs identified...
November 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825132/identification-of-klk10-as-a-therapeutic-target-to-reverse-trastuzumab-resistance-in-breast-cancer
#14
Zhuo Wang, Beihong Ruan, Yi Jin, Yulong Zhang, Jiaqiu Li, Liyuan Zhu, Wenxia Xu, Lifeng Feng, Hongchuan Jin, Xian Wang
Trastuzumab, the first antibody widely used in anti-HER2 targeted therapy, dramatically improved the overall outcome of HER2 positive breast cancer patients. However, trastuzumab resistance emerged as a major problem in its clinical application. In order to explore mechanisms underlying trastuzumab resistance, we performed RNA-Seq to analyze the gene expression variation in trastuzumab resistant breast cancer cell line. The sequencing result was then combined with the relevant data in TCGA database to conduct a co-expression analysis...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27816361/genetic-variants-in-cd44-and-mat1a-confer-susceptibility-to-acute-skin-reaction-in-breast-cancer-patients-undergoing-radiation-therapy
#15
Kamalesh Dattaram Mumbrekar, Satish Rao Bola Sadashiva, Shama Prasada Kabekkodu, Donald Jerard Fernandes, Bejadi Manjunath Vadhiraja, Tomo Suga, Yoshimi Shoji, Fumiaki Nakayama, Takashi Imai, Kapaettu Satyamoorthy
PURPOSE: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage-repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker...
September 20, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27812285/a-multifaceted-role-for-myd88-dependent-signaling-in-progression-of-murine-mammary-carcinoma
#16
Mary J Higgins, Antonio Serrano, Kofi Y Boateng, Victoria A Parsons, Tiffany Phuong, Alyssa Seifert, Jacob M Ricca, Kyle C Tucker, Alec S Eidelman, Maureen A Carey, Robert A Kurt
Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal-regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C-C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth...
2016: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/27784183/investigating-mirna-mrna-regulatory-networks-using-crosslinking-immunoprecipitation-methods-for-biomarker-and-target-discovery-in-cancer
#17
Mireia Mato Prado, Adam E Frampton, Elisa Giovannetti, Justin Stebbing, Leandro Castellano, Jonathan Krell
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Recently, different experimental approaches, such as RNA Sequencing, crosslinking immunoprecipitation (CLIP) methods and its variations, together with computational approaches have been developed to elucidate the miRNA-mRNA targetome. Areas covered: This report focuses on comparing the different experimental and computational approaches, describing their advantages and disadvantages and providing several examples of preclinical (in vitro and in vivo) and clinical studies that have identified miRNA target genes in various tumour types, including breast, ovary, colorectal and pancreas...
November 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27780928/sin3a-and-sin3b-differentially-regulate-breast-cancer-metastasis
#18
Monica J Lewis, Jianzhong Liu, Emily Falk Libby, Minnkyong Lee, Nigel P S Crawford, Douglas R Hurst
SIN3 corepressor complexes play important roles in both normal development and breast cancer. Mammalian cells have two paralogs of SIN3 (SIN3A and SIN3B) that are encoded by distinct genes and have unique functions in many developmental processes. However, specific roles for SIN3A and SIN3B in breast cancer progression have not been characterized. We generated stable knockdown cells of SIN3 paralogs individually and in combination using three non-overlapping shRNA. Stable knockdown of SIN3B caused a significant decrease in transwell invasion through Matrigel and decreased the number of invasive colonies when grown in a 3D extracellular matrix...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27774939/-knockdown-of-sost-in-mda-mb-231-breast-cancer-cells-increase-mg-63-osteoblast-like-cell-function-in-co-culture-system
#19
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
https://www.readbyqxmd.com/read/27774452/rna-sequencing-of-formalin-fixed-paraffin-embedded-specimens-for-gene-expression-quantification-and-data-mining
#20
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
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