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RNA sequencing Breast Cancer

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https://www.readbyqxmd.com/read/29330289/brca1-through-its-e3-ligase-activity-regulates-the-transcription-factor-oct1-and-carbohydrate-metabolism
#1
Karina Vázquez-Arreguín, Jessica Maddox, Jinsuk Kang, Dongju Park, Reuben R Cano, Rachel E Factor, Thomas Ludwig, Dean Tantin
The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other processes that remain incompletely defined. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1 (POU2F1), a transcription factor with pro-glycolytic and tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells towards a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330282/population-dependent-intron-retention-and-dna-methylation-in-breast-cancer
#2
Dongwook Kim, Manu Shivakumar, Seonggyun Han, Michael S Sinclair, Youngji Lee, Yonglan Zheng, Olufunmilayo I Olopade, Dokyoon Kim, Younghee Lee
Regulation of gene expression by DNA methylation in gene promoter regions is well-studied; however, the effects of methylation in the gene body (exons and introns) on gene expression are comparatively understudied. Recently, hyper-methylation has been implicated in the inclusion of alternatively spliced exons; moreover, exon recognition can be enhanced by recruiting the methyl-CpG-binding protein (MeCP2) to hyper-methylated sites. This study examines if methylation status of an intron is correlated with how frequently the intron is retained during splicing using DNA methylation and RNA sequencing (RNA-seq) data from breast cancer tissue specimens in The Cancer Genome Atlas (TCGA)...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29322784/bioinformatic-analysis-of-changes-in-rna-polymerase-ii-transcription-stimulated-by-estradiol-in-mcf7-cells
#3
J Wu, Y Cai, G Zhao
Estradiol (E2) is the most potent estrogen and RNA polymerase II (Pol II) regulates a great mass of gene expression. This study was designed to illustrate the mechanisms of estrogen-dependent human breast cancer (BC) through Pol II. ChIP-seq data, DNase-seq data and other sequencing data of human BC MCF-7 cells were downloaded from Gene Expression Omnibus database. Each of these datasets included one control and one E2 treated sample. Sequence alignment was performed and Pol II factor binding signal was determined...
2018: Neoplasma
https://www.readbyqxmd.com/read/29320459/the-landscape-of-small-non-coding-rnas-in-triple-negative-breast-cancer
#4
Yan Guo, Hui Yu, Jing Wang, Quanhu Sheng, Shilin Zhao, Ying-Yong Zhao, Brian D Lehmann
Triple-negative breast cancer (TNBC) is an operational term for breast cancers lacking targetable estrogen receptor expression and HER2 amplifications. TNBC is, therefore, inherently heterogeneous, and is associated with worse prognosis, greater rates of metastasis, and earlier onset. TNBC displays mutational and transcriptional diversity, and distinct mRNA transcriptional subtypes exhibiting unique biology. High-throughput sequencing has extended cancer research far beyond protein coding regions that include non-coding small RNAs, such as miRNA, isomiR, tRNA, snoRNAs, snRNA, yRNA, 7SL, and 7SK...
January 10, 2018: Genes
https://www.readbyqxmd.com/read/29312586/glucose-impairs-tamoxifen-responsiveness-modulating-connective-tissue-growth-factor-in-breast-cancer-cells
#5
Maria Rosaria Ambrosio, Vittoria D'Esposito, Valerio Costa, Domenico Liguoro, Francesca Collina, Monica Cantile, Nella Prevete, Carmela Passaro, Giusy Mosca, Michelino De Laurentiis, Maurizio Di Bonito, Gerardo Botti, Renato Franco, Francesco Beguinot, Alfredo Ciccodicola, Pietro Formisano
Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29304755/computational-approach-to-discriminate-human-and-mouse-sequences-in-patient-derived-tumour-xenografts
#6
Maurizio Callari, Ankita Sati Batra, Rajbir Nath Batra, Stephen-John Sammut, Wendy Greenwood, Harry Clifford, Colin Hercus, Suet-Feung Chin, Alejandra Bruna, Oscar M Rueda, Carlos Caldas
BACKGROUND: Patient-Derived Tumour Xenografts (PDTXs) have emerged as the pre-clinical models that best represent clinical tumour diversity and intra-tumour heterogeneity. The molecular characterization of PDTXs using High-Throughput Sequencing (HTS) is essential; however, the presence of mouse stroma is challenging for HTS data analysis. Indeed, the high homology between the two genomes results in a proportion of mouse reads being mapped as human. RESULTS: In this study we generated Whole Exome Sequencing (WES), Reduced Representation Bisulfite Sequencing (RRBS) and RNA sequencing (RNA-seq) data from samples with known mixtures of mouse and human DNA or RNA and from a cohort of human breast cancers and their derived PDTXs...
January 5, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29301303/natural-antisense-transcripts-molecular-mechanisms-and-implications-in-breast-cancers
#7
REVIEW
Guillaume Latgé, Christophe Poulet, Vincent Bours, Claire Josse, Guy Jerusalem
Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation...
January 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29285045/optimization-of-rna-extraction-from-formalin-fixed-paraffin-embedded-blocks-for-targeted-next-generation-sequencing
#8
Yoojin Choi, Aeree Kim, Jinkyoung Kim, Jinhwan Lee, Soo Yeon Lee, Chungyeul Kim
Purpose: Breast cancer has a high prevalence in Korea. To achieve personalized therapy for breast cancer, long-term follow-up specimens are needed for next-generation sequencing (NGS) and multigene analysis. Formalin-fixed paraffin-embedded (FFPE) samples are easier to store than fresh frozen (FF) samples. The objective of this study was to optimize RNA extraction from FFPE blocks for NGS. Methods: RNA quality from FF and FFPE tissues (n=5), expected RNA amount per unit area, the relationship between archiving time and quantity/quality of FFPE-extracted RNA (n=14), differences in quantitative real-time polymerase chain reaction (qRT-PCR) and NGS results, and comparisons of both techniques with tissue processing at different institutions (n=96) were determined in this study...
December 2017: Journal of Breast Cancer
https://www.readbyqxmd.com/read/29244808/fgmd-a-novel-approach-for-functional-gene-module-detection-in-cancer
#9
Daeyong Jin, Hyunju Lee
With the increasing availability of multi-dimensional biological datasets for the same samples (i.e., gene expression, microRNAs, copy numbers, mutations, methylations), it has now become possible to systematically understand the regulatory mechanisms operating in a cancer cell. For this task, it is important to discover a set of co-expressed genes with functions, representing a so-called functional gene module, because co-expressed genes tend to be co-regulated by the same regulators, including transcription factors, microRNAs, and copy number aberrations...
2017: PloS One
https://www.readbyqxmd.com/read/29234122/transcriptome-wide-analysis-of-natural-antisense-transcripts-shows-their-potential-role-in-breast-cancer
#10
Stephane Wenric, Sonia ElGuendi, Jean-Hubert Caberg, Warda Bezzaou, Corinne Fasquelle, Benoit Charloteaux, Latifa Karim, Benoit Hennuy, Pierre Frères, Joëlle Collignon, Meriem Boukerroucha, Hélène Schroeder, Fabrice Olivier, Véronique Jossa, Guy Jerusalem, Claire Josse, Vincent Bours
Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense transcripts (ncNAT) are RNA sequences that are complementary and overlapping to those of either protein-coding (PCT) or non-coding transcripts. Several ncNATs were described as regulating protein coding gene expression on the same loci, and they are expected to act more frequently in cis compared to other ncRNAs that commonly function in trans...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29227193/ddx5-p68-associated-lncrna-loc284454-is-differentially-expressed-in-human-cancers-and-modulates-gene-expression
#11
Monalisa Das, Arun Renganathan, Shrinivas Nivrutti Dighe, Utsa Bhaduri, Abhijith Shettar, Geetashree Mukherjee, Paturu Kondaiah, Manchanahalli R Satyanarayana Rao
Long non-coding RNAs (lncRNAs) are emerging as important players in regulation of gene expression in higher eukaryotes. DDX5/p68 RNA helicase protein which is involved in splicing of precursor mRNAs also interacts with lncRNAs like, SRA and mrhl, to modulate gene expression. We performed RIP-seq analysis in HEK293T cells to identify the complete repertoire of DDX5/p68 interacting transcripts including 73 single exonic (SE) lncRNAs. The LOC284454 lncRNA is the second top hit of the list of SE lncRNAs which we have characterized in detail for its molecular features and cellular functions...
December 11, 2017: RNA Biology
https://www.readbyqxmd.com/read/29225342/differentiation-dynamics-of-mammary-epithelial-cells-revealed-by-single-cell-rna%C3%A2-sequencing
#12
Karsten Bach, Sara Pensa, Marta Grzelak, James Hadfield, David J Adams, John C Marioni, Walid T Khaled
Characterising the hierarchy of mammary epithelial cells (MECs) and how they are regulated during adult development is important for understanding how breast cancer arises. Here we report the use of single-cell RNA sequencing to determine the gene expression profile of MECs across four developmental stages; nulliparous, mid gestation, lactation and post involution. Our analysis of 23,184 cells identifies 15 clusters, few of which could be fully characterised by a single marker gene. We argue instead that the epithelial cells-especially in the luminal compartment-should rather be conceptualised as being part of a continuous spectrum of differentiation...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29221160/circular-rna-profile-indicates-circular-rna-vrk1-is-negatively-related-with-breast-cancer-stem-cells
#13
Ningning Yan, Haiyan Xu, Jinnan Zhang, Liang Xu, Yanyun Zhang, Le Zhang, Yingchun Xu, Fengchun Zhang
Circular RNAs (circRNAs), a novel type of noncoding RNAs (ncRNAs), have been shown to be implicated in biological processes including cancer as gene expression regulators. However, the roles of circRNAs in cancer stem cells (CSCs) have been unexplored. In the present study, we screened the circRNA profile in breast cancer stem cells (BCSCs) using RNA-Sequencing. Here, 27 circRNAs were found to be aberrantly expressed. Of these, 19 circRNAs were downregulated and 8 were upregulated and some of these circRNAs were validated by Q-PCR...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220513/integrating-5hmc-and-gene-expression-data-to-infer-regulatory-mechanisms
#14
Cristina Mitrea, Priyanga Wijesinghe, Greg Dyson, Adéle Kruger, Douglas M Ruden, Sorin Draghici, Aliccia Bollig-Fischer
Motivation: Epigenetic mechanisms are known to play a major role in breast cancer. However, the role of 5-hydroxymethylcytosine (5hmC) remains understudied. We hypothesize that 5hmC mediates redox regulation of gene expression in an aggressive subtype known as triple negative breast cancer (TNBC). To address this, our objective was to highlight genes that may be the target of this process by identifying redox-regulated, antioxidant-sensitive, gene-localized 5hmC changes associated with mRNA changes in TNBC cells...
December 6, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29214215/genomic-and-transcriptomic-heterogeneity-in-metaplastic-carcinomas-of-the-breast
#15
Salvatore Piscuoglio, Charlotte K Y Ng, Felipe C Geyer, Kathleen A Burke, Catherine F Cowell, Luciano G Martelotto, Rachael Natrajan, Tatiana Popova, Christopher A Maher, Raymond S Lim, Ino de Bruijn, Odette Mariani, Larry Norton, Anne Vincent-Salomon, Britta Weigelt, Jorge S Reis-Filho
Metaplastic breast cancer (MBC) is a rare special histologic type of triple-negative breast cancer, characterized by the presence of neoplastic cells showing differentiation towards squamous epithelium and/or mesenchymal elements. Here we sought to define whether histologically distinct subgroups of MBCs would be underpinned by distinct genomic and/or transcriptomic alterations. Microarray-based copy number profiling identified limited but significant differences between the distinct MBC subtypes studied here, despite the limited sample size (n = 17)...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29194591/a-mutational-comparison-of-adult-and-adolescent-and-young-adult-aya-colon-cancer
#16
James V Tricoli, Lisa A Boardman, Rajesh Patidar, Sivasish Sindiri, Jin S Jang, William D Walsh, Paul M McGregor, Corinne E Camalier, Michele G Mehaffey, Wayne L Furman, Armita Bahrami, P Mickey Williams, Chih-Jian Lih, Barbara A Conley, Javed Khan
BACKGROUND: It is possible that the relative lack of progress in treatment outcomes among adolescent and young adult (AYA) patients with cancer is caused by a difference in disease biology compared with the corresponding diseases in younger and older individuals. There is evidence that colon cancer is more aggressive and has a poorer prognosis in AYA patients than in older adult patients. METHODS: To further understand the molecular basis for this difference, whole-exome sequencing was conducted on a cohort of 30 adult, 30 AYA, and 2 pediatric colon cancers...
November 30, 2017: Cancer
https://www.readbyqxmd.com/read/29193730/the-3p14-2-tumour-suppressor-adamts9-is-inactivated-by-promoter-cpg-methylation-and-inhibits-tumour-cell-growth-in-breast-cancer
#17
Bianfei Shao, Yixiao Feng, Hongbin Zhang, Fang Yu, Qianqian Li, Cui Tan, Hongying Xu, Jianming Ying, Lili Li, Dejuan Yang, Weiyan Peng, Jun Tang, Shuman Li, Guosheng Ren, Qian Tao, Tingxiu Xiang
Chromosome region 3p12-14 is an important tumour suppressor gene (TSG) locus for multiple cancers. ADAMTS9, a member of the metalloprotease large family, has been identified as a candidate 3p14.2 TSG inactivated by aberrant promoter CpG methylation in several carcinomas, but little known about its expression and function in breast cancer. In this report, ADAMTS9 expression and methylation was analysed in breast cancer cell lines and tissue samples. ADAMTS9 RNA was significantly down-regulated in breast cancer cell lines (6/8)...
November 29, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29192415/dna-methyltransferase-inhibitors-influence-on-the-diras3-and-stat3-expression-and-in-vitro-migration-of-ovarian-and-breast-cancer-cells
#18
Ewa Maria Nowak, Marta Poczęta, Dominik Bieg, Ilona Bednarek
OBJECTIVES: Downregulation of DIRAS3 (DIRAS family, GTP-binding Ras-like 3) is related to ovarian and breast cancer progression. A possible mechanism that silences this gene is the promoter region DNA methylation. The potential reversibility of this epigenetic mechanism makes it more attractive candidate for new mode of cancer treatment. DIRAS3 regulates cell cycle, tumor dormancy and inhibits cancer cell growth and motility, all of which may indirectly depend on interaction with STAT3 (Signal Transducer and Activator of Transcription 3) classified as a potential oncogene...
2017: Ginekologia Polska
https://www.readbyqxmd.com/read/29192217/decreased-mirna-expression-in-klinefelter-syndrome
#19
Laura Cimino, Michele Salemi, Rossella Cannarella, Rosita A Condorelli, Giorgio Giurato, Giovanna Marchese, Sandro La Vignera, Aldo E Calogero
The widelyvariable phenotypic spectrum and the different severity of symptoms in men with Klinefelter syndrome (KS) suggest a role for epigenetic mediators. Therefore, the aim of this study is to evaluate the possible involvement of miRNAs in the clinical manifestations of KS. To accomplish this, we performed a transcriptome analysis in peripheral blood mononuclear cells (PBMCs) of 10 non-mosaic KS patients, 10 aged-matched healthy men and 10 aged-matched healthy female controls with normal karyotype. After RNA extraction from PBMC and the preparation of RNA libraries, the samples were sequenced using next generation high-throughput sequencing technology...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29190829/a-comprehensive-analysis-of-breast-cancer-microbiota-and-host-gene-expression
#20
Kevin J Thompson, James N Ingle, Xiaojia Tang, Nicholas Chia, Patricio R Jeraldo, Marina R Walther-Antonio, Karunya K Kandimalla, Stephen Johnson, Janet Z Yao, Sean C Harrington, Vera J Suman, Liewei Wang, Richard L Weinshilboum, Judy C Boughey, Jean-Pierre Kocher, Heidi Nelson, Matthew P Goetz, Krishna R Kalari
The inflammatory tumoral-immune response alters the physiology of the tumor microenvironment, which may attenuate genomic instability. In addition to inducing inflammatory immune responses, several pathogenic bacteria produce genotoxins. However the extent of microbial contribution to the tumor microenvironment biology remains unknown. We utilized The Cancer Genome Atlas, (TCGA) breast cancer data to perform a novel experiment utilizing unmapped and mapped RNA sequencing read evidence to minimize laboratory costs and effort...
2017: PloS One
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