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RNA sequencing Breast Cancer

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https://www.readbyqxmd.com/read/28063307/sharpin-facilitates-p53-degradation-in-breast-cancer-cells
#1
Huijie Yang, Sifan Yu, Weilong Wang, Xin Li, Yingxiang Hou, Zhenhua Liu, Yuanyuan Shi, Kun Mu, Gang Niu, Juntao Xu, Hui Wang, Jian Zhu, Ting Zhuang
The ubiquitin binding protein SHAPRIN is highly expressed in human breast cancer, one of the most frequent female malignancies worldwide. Here, we perform SHARPIN depletion in breast cancer cells together with RNA sequencing. The global expression profiling showed p53 signaling as a potential SHARPIN target. SHARPIN depletion decreased cell proliferation, which effect could be rescue by p53 knocking down. Depletion SHARPIN significantly increases p53 protein level and its target genes in multiple breast cancer cell lines...
January 4, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28062977/angiopoietin-pathway-gene-expression-associated-with-poor-breast-cancer-survival
#2
Rajesh Ramanathan, Amy L Olex, Mikhail Dozmorov, Harry D Bear, Leopoldo Jose Fernandez, Kazuaki Takabe
PURPOSE: Angiogenesis is one of the hallmarks of cancer and is essential for cancer progression and metastasis. However, clinical trials with vascular endothelial growth factor (VEGF) pathway inhibitors have failed to show overall survival benefit in breast cancer. Targeted therapy against the angiopoietin pathway, a downstream angiogenesis cascade, could be effective in breast cancer. This study investigates the association of angiopoietin pathway gene expression with breast cancer survival using a "big data" approach employing RNA sequencing data from The Cancer Genome Atlas (TCGA)...
January 6, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28009814/a-novel-pathogenic-brca1-splicing-variant-produces-partial-intron-retention-in-the-mature-messenger-rna
#3
Maria Valeria Esposito, Marcella Nunziato, Flavio Starnone, Antonella Telese, Alessandra Calabrese, Giuseppe D'Aiuto, Pietro Pucci, Massimiliano D'Aiuto, Francisco Baralle, Valeria D'Argenio, Francesco Salvatore
About 10% of all breast cancers arise from hereditary mutations that increase the risk of breast and ovarian cancers; and about 25% of these are associated with the BRCA1 or BRCA2 genes. The identification of BRCA1/BRCA2 mutations can enable physicians to better tailor the clinical management of patients; and to initiate preventive measures in healthy carriers. The pathophysiological significance of newly identified variants poses challenges for genetic counseling. We characterized a new BRCA1 variant discovered in a breast cancer patient during BRCA1/2 screening by next-generation sequencing...
December 21, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27993792/network-guided-modelling-allows-tumor-type-independent-prediction-of-sensitivity-to-all-trans-retinoic-acid
#4
M Bolis, E Garattini, G Paroni, A Zanetti, M Kurosaki, T Castrignano', S K Garattini, F Biancardi, M M Barzago, M Gianni', M Terao, L Pattini, M Fratelli
BACKGROUND: All-trans retinoic acid (ATRA) is a differentiating agent used in the treatment of acute-promyelocytic-leukemia and it is under-exploited in other malignancies despite its low systemic toxicity. A rational/personalized use of ATRA requires development of predictive tools allowing identification of sensitive cancer types and responsive individuals. MATERIALS AND METHODS: RNA-Sequencing data for 10080 patients and 33 different tumor-types were derived from the TCGA and Leucegene datasets and completely re-processed...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27982086/gene-expression-in-local-stroma-reflects-breast-tumor-states-and-predicts-patient-outcome
#5
Russell Bainer, Casey Frankenberger, Daniel Rabe, Gary An, Yoav Gilad, Marsha Rich Rosner
The surrounding microenvironment has been implicated in the progression of breast tumors to metastasis. However, the degree to which metastatic breast tumors locally reprogram stromal cells as they disrupt tissue boundaries is not well understood. We used species-specific RNA sequencing in a mouse xenograft model to determine how the metastasis suppressor RKIP influences transcription in a panel of paired tumor and stroma tissues. We find that gene expression in metastatic breast tumors is pervasively correlated with gene expression in local stroma of both mouse xenografts and human patients...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27965971/profiling-of-the-predicted-circular-rnas-in-ductal-in-situ-and-invasive-breast-cancer-a-pilot-study
#6
Marco Galasso, Giorgio Costantino, Lorenzo Pasquali, Linda Minotti, Federica Baldassari, Fabio Corrà, Chiara Agnoletto, Stefano Volinia
The recent advantage obtained by next generation sequencing allows a depth investigation of a new "old" kind of noncoding transcript, the circular RNAs. Circular RNAs are nontranslated RNAs, typically nonpolyadenylated, with a resistance to exonucleases that gives them the ability to be more stable than the common linear RNA isoforms. We used a bioinformatic detection tool (CIRCexplorer) to research predictive circRNAs from the next generation sequenced data of five samples of ductal in situ carcinoma (DCIS) and matched adjacent invasive ductal carcinoma (IDC)...
2016: International Journal of Genomics
https://www.readbyqxmd.com/read/27959926/predictors-of-chemosensitivity-in-triple-negative-breast-cancer-an-integrated-genomic-analysis
#7
Tingting Jiang, Weiwei Shi, Vikram B Wali, Lőrinc S Pongor, Charles Li, Rosanna Lau, Balázs Győrffy, Richard P Lifton, William F Symmans, Lajos Pusztai, Christos Hatzis
BACKGROUND: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients. METHODS AND FINDINGS: We performed whole exome sequencing on 29 TNBC cases from the MD Anderson Cancer Center (MDACC) selected because they had either pCR (n = 18) or extensive residual disease (n = 11) after neoadjuvant chemotherapy, with cases from The Cancer Genome Atlas (TCGA; n = 144) and METABRIC (n = 278) cohorts serving as validation cohorts...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27935425/how-is-herstatin-a-tumor-suppressor-splice-variant-of-the-oncogene-her2-regulated
#8
Marco Silipo, Hannah Gautrey, Swapna Satam, Thomas Lennard, Alison Tyson-Capper
The human epidermal growth factor receptor 2 (HER2)/receptor tyrosine-protein kinasebB-2 (ERBB2) is overexpressed in 20-30% of breast tumors leading to faster growing and more aggressive tumors. Alternative splicing generates a functionally distinct HER2 variant called Herstatin, which is produced by the inclusion of intron 8. Herstatin acts as a tumor suppressor by effectively blocking HER2 activity and cell proliferation, while promoting apoptosis. In the present study we investigated HER2 pre-mRNA regulatory sequences and splicing factors which regulate the alternative splicing of Herstatin...
December 9, 2016: RNA Biology
https://www.readbyqxmd.com/read/27901097/sequencing-based-breast-cancer-diagnostics-as-an-alternative-to-routine-biomarkers
#9
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
#10
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
#11
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
#12
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
#13
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...
January 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27879434/5-terminal-nucleotide-variations-in-human-cytoplasmic-trnahisgug-and-its-5-halves
#14
Megumi Shigematsu, Yohei Kirino
Transfer RNAs (tRNAs) are fundamental adapter components of translational machinery. tRNAs can further serve as a source of tRNA-derived noncoding RNAs that play important roles in various biological processes beyond translation. Among all species of tRNAs, tRNA(HisGUG) 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 that can distinctively quantify human mature cytoplasmic tRNA(HisGUG) containing G-1, U-1, A-1, or C-1 or lacking the -1 nucleotide (starting from G1)...
February 2017: RNA
https://www.readbyqxmd.com/read/27874091/hmga1p7-pseudogene-regulates-h19-and-igf2-expression-by-a-competitive-endogenous-rna-mechanism
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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