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RNA sequencing Breast Cancer

Eva Vargas, Eloy Povedano, Víctor Ruiz-Valdepeñas Montiel, Rebeca M Torrente-Rodríguez, Mohamed Zouari, Juan José Montoya, Noureddine Raouafi, Susana Campuzano, José M Pingarrón
This work reports an amperometric biosensor for the determination of miRNA-21, a relevant oncogene. The methodology involves a competitive DNA-target miRNA hybridization assay performed on the surface of magnetic microbeads (MBs) and amperometric transduction at screen-printed carbon electrodes (SPCEs). The target miRNA competes with a synthetic fluorescein isothiocyanate (FITC)-modified miRNA with an identical sequence for hybridization with a biotinylated and complementary DNA probe (b-Cp) immobilized on the surface of streptavidin-modified MBs (b-Cp-MBs)...
March 15, 2018: Sensors
Zhengda Sun, Chih-Yang Wang, Devon A Lawson, Serena Kwek, Hugo Gonzalez Velozo, Mark Owyong, Ming-Derg Lai, Lawrence Fong, Mark Wilson, Hua Su, Zena Werb, Daniel L Cooke
Tumor endothelial cells (TEC) play an indispensible role in tumor growth and metastasis although much of the detailed mechanism still remains elusive. In this study we characterized and compared the global gene expression profiles of TECs and control ECs isolated from human breast cancerous tissues and reduction mammoplasty tissues respectively by single cell RNA sequencing (scRNA-seq). Based on the qualified scRNA-seq libraries that we made, we found that 1302 genes were differentially expressed between these two EC phenotypes...
February 16, 2018: Oncotarget
Tia H Turner, Mohammad A Alzubi, Sahib S Sohal, Amy L Olex, Mikhail G Dozmorov, J Chuck Harrell
PURPOSE: Basal-like breast cancers are aggressive and often metastasize to vital organs. Treatment is largely limited to chemotherapy. This study aims to characterize the efficacy of cancer therapeutics in vitro and in vivo within the primary tumor and metastatic setting, using patient-derived xenograft (PDX) models. METHODS: We employed two basal-like, triple-negative PDX models, WHIM2 and WHIM30. PDX cells, obtained from mammary tumors grown in mice, were treated with twelve cancer therapeutics to evaluate their cytotoxicity in vitro...
March 12, 2018: Breast Cancer Research and Treatment
Minlan Yang, Hairi Li, Yanru Li, Yang Ruan, Chengshi Quan
Multidrug resistance (MDR) is a major problem in the treatment of breast cancer. In the present study, next-generation sequencing technology was employed to identify differentially expressed genes in MCF‑7/MDR cells and MCF‑7 cells, and aimed to investigate the underlying molecular mechanisms of MDR in breast cancer. Differentially expressed genes between MCF‑7/MDR and MCF‑7 cells were selected using software; a total of 2085 genes were screened as differentially expressed in MCF‑7/MDR cells. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database...
March 7, 2018: Molecular Medicine Reports
Yoshimasa Miyagawa, Yosuke Matsushita, Hiromu Suzuki, Masato Komatsu, Tetsuro Yoshimaru, Ryuichiro Kimura, Ayako Yanai, Junko Honda, Akira Tangoku, Mitsunori Sasa, Yasuo Miyoshi, Toyomasa Katagiri
Triple-negative breast cancer (TNBC), defined as breast cancer lacking estrogen- and progesterone‑receptor expression and human epidermal growth factor receptor 2 (HER2) amplification, is a heterogeneous disease. RNA-sequencing analysis of 15 TNBC specimens and The Cancer Genome Atlas-TNBC dataset analysis identified the frequent downregulation of leucine-rich repeat-containing 26 (LRRC26), which negatively regulates nuclear factor-κB (NF-κB) signaling, in TNBC tissues. Quantitative polymerase chain reaction and bisulfite pyrosequencing analyses revealed that LRRC26 was frequently silenced in TNBC tissues and cell lines as a result of promoter methylation...
March 5, 2018: International Journal of Oncology
Trung Nghia Vu, Quin F Wills, Krishna R Kalari, Nifang Niu, Liewei Wang, Yudi Pawitan, Mattias Rantalainen
Motivation: RNA sequencing of single cells enables characterization of transcriptional heterogeneity in seemingly homogeneous cell populations. Single-cell sequencing has been applied in a wide range of researches fields. However, few studies have focus on characterization of isoform-level expression patterns at the single-cell level. In this study we propose and apply a novel method, ISOform-Patterns (ISOP), based on mixture modeling, to characterize the expression patterns of isoform pairs from the same gene in single-cell isoform-level expression data...
February 27, 2018: Bioinformatics
Marni B Siegel, Xiaping He, Katherine A Hoadley, Alan Hoyle, Julia B Pearce, Amy L Garrett, Sunil Kumar, Vincent J Moylan, Claudia M Brady, Amanda Ed Van Swearingen, David Marron, Gaorav P Gupta, Leigh B Thorne, Niamh Kieran, Chad Livasy, Elaine R Mardis, Joel S Parker, Mengjie Chen, Carey K Anders, Lisa A Carey, Charles M Perou
Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading...
February 26, 2018: Journal of Clinical Investigation
Peng Ye, Cheng Fang, Hui Zeng, Yu Shi, Zhongya Pan, Nairui An, Keli He, Li Zhang, Xinghua Long
Tamoxifen (TAM) resistance has become a severe problem for endocrine therapy of breast cancer. The present study investigated the association between microRNA (miRNA) expression and TAM resistance in breast cancer. The TAM-resistant breast cancer MCF-7C and MCF-7T cell lines were established using the human breast cancer cell line MCF-7 as the parental cell line and 4-hydroxytamoxifen (OHT) as the screening drug in vitro . The MCF-7C cell line was established by dose stepwise induction beginning with a low concentration of OHT; the MCF-7T cell line was established by temporal stepwise induction beginning with a high concentration of OHT...
March 2018: Oncology Letters
Yan Zhang, Xin Li, Dianshuang Zhou, Hui Zhi, Peng Wang, Yue Gao, Maoni Guo, Ming Yue, Yanxia Wang, Weitao Shen, Shangwei Ning, Yixue Li, Xia Li
Differences in individual drug responses is an obstacle to progression in cancer treatment, and predicting responses would help to plan treatment. The accumulation of cancer molecular profiling and drug response data provides opportunities and challenges to identify novel molecular signatures and mechanisms of tumor responsiveness to drugs. This study evaluated drug responses with a competing endogenous RNA (ceRNA) system that depended on competition between diverse RNA species. We identified drug response-related ceRNAs (DRCEs) by combining the sequence and expression data of long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) and the survival data of cancer patients treated with drugs...
February 21, 2018: Molecular Oncology
Yasuyuki Kanke, Akihiko Shimomura, Motonobu Saito, Takayuki Honda, Kouya Shiraishi, Yoko Shimada, Reiko Watanabe, Hiroshi Yoshida, Masayuki Yoshida, Chikako Shimizu, Kazuaki Takahashi, Hirohiko Totsuka, Hideaki Ogiwara, Sou Hirose, Koji Kono, Kenji Tamura, Aikou Okamoto, Takayuki Kinoshita, Tomoyasu Kato, Takashi Kohno
There has been little improvement in the prognosis for adolescent and young adult (AYA) tumor patients. Hence, there is an urgent need to understand the etiology of tumor development and identify actionable gene aberrations to improve prevention and therapy. Here, 76 sporadic tumors (48 breast, 22 ovarian, and six uterine) from 76 AYA females (age range, 25-39 years) were subjected to whole exome and RNA sequencing to determine their mutational signatures and actionable gene profiles. Two individuals with breast cancer (4...
January 19, 2018: Oncotarget
Nigel G Kooreman, Youngkyun Kim, Patricia E de Almeida, Vittavat Termglinchan, Sebastian Diecke, Ning-Yi Shao, Tzu-Tang Wei, Hyoju Yi, Devaveena Dey, Raman Nelakanti, Thomas P Brouwer, David T Paik, Idit Sagiv-Barfi, Arnold Han, Paul H A Quax, Jaap F Hamming, Ronald Levy, Mark M Davis, Joseph C Wu
Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models...
February 8, 2018: Cell Stem Cell
Laura W Bowers, Emily L Rossi, Shannon B McDonell, Steven S Doerstling, Subreen A Khatib, Claire G Lineberger, Jody E Albright, Xiaohu Tang, Linda A deGraffenried, Stephen D Hursting
Obesity is associated with poor prognosis in triple-negative breast cancer (TNBC). Preclinical models of TNBC were used to test the hypothesis that increased leptin signaling drives obesity-associated TNBC development by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal-like, triple-negative mammary tumors, received either a control diet (10% kcal from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42 weeks (n=15/group)...
February 16, 2018: Molecular Cancer Research: MCR
Nicola Aceto, Aditya Bardia, Ben S Wittner, Maria C Donaldson, Ryan O'Keefe, Amanda Engstrom, Francesca Bersani, Yu Zheng, Valentine Comaills, Kira Niederhoffer, Huili Zhu, Olivia MacKenzie, Toshi Shioda, Dennis Sgroi, Ravi Kapur, David T Ting, Beverly Moy, Sridhar Ramaswamy, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing (RNA-seq) was performed of circulating tumor cells (CTCs) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7...
February 16, 2018: Molecular Cancer Research: MCR
Danai Fimereli, Debora Fumagalli, David Brown, David Gacquer, Françoise Rothé, Roberto Salgado, Denis Larsimont, Christos Sotiriou, Vincent Detours
The advent of next generation sequencing technologies has boosted the interest in exploring the role of fusion genes in the development and progression of solid tumors. In breast cancer, most of the detected gene fusions seem to be "passenger" events while the presence of recurrent and driver fusions is still under study. We performed RNA sequencing in 55 well-characterized breast cancer samples and 10 adjacent normal breast tissues, complemented by an analysis of SNP array data. We explored the presence of fusion genes and defined their association with breast cancer subtypes, clinical-pathologic characteristics and copy number aberrations...
February 13, 2018: Genes, Chromosomes & Cancer
Saki Matsui, Naofumi Kagara, Chieko Mishima, Yasuto Naoi, Masafumi Shimoda, Atsushi Shimomura, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
Tumor-specific promoter hypermethylation of large tumor suppressor, homolog 2 (LATS2), a tumor suppressor gene, has been investigated using methylation-specific polymerase chain reaction (MSP) assays in different types of human cancer producing conflicting results. The aim of the present study was to evaluate the methylation status of the LATS2 promoter region using bisulfite sequencing with a next generation sequencer for breast cancer. In the 11 patients enrolled in the present study, the LATS2 promoter methylation index (MI) was uniformly high in tumor and normal tissues of the breast (median, 84...
February 2018: Oncology Letters
Jingcheng Zhang, Bin Wei, Huixian Hu, Fanrong Liu, Yan Tu, Fang He
Micro (mi)RNAs are an endogenous non-coding small RNA comprised of 19-26 nucleotides. miRNAs regulate gene expression through the recognition of its 'seed sequence' and interactions with 3'-untranslated region of target miRNAs. Previous studies identified that miRNAs are associated with the onset and development of breast cancer and that a number of mutations in the coding DNA sequence of miRNAs affect its expression. Therefore, the present study aimed to screen differentially expressed miRNAs using miRNA expression profile chips to analyze the expression of miRNA (miR)-205 in 12 breast cell lines of different metastatic performance and benign proliferative variation as well as breast cancer via in-situ hybridization, and screen out single-nucleotide polymorphisms (SNPs) in the miR-205 coding gene region...
February 2018: Oncology Letters
Huijie Yang, Na Yu, Juntao Xu, Xiaosheng Ding, Wei Deng, Guojin Wu, Xin Li, Yingxiang Hou, Zhenhua Liu, Yan Zhao, Min Xue, Sifan Yu, Beibei Wang, Xiumin Li, Gang Niu, Hui Wang, Jian Zhu, Ting Zhuang
BACKGROUND: Estrogen receptor alpha (ER alpha) is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. ER alpha positive breast cancer can be well controlled by ER alpha modulators, such as tamoxifen. However, tamoxifen resistance is commonly observed by altered ER alpha signaling. Thus, further understanding of the molecular mechanisms, which regulates ER alpha signaling, is important to improve breast cancer therapy. METHODS: SMURF1 and ER alpha protein expression levels were measured by western blot, while the ER alpha target genes were measured by real-time PCR...
February 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
Fan Wang, Zachariah Dohogne, Jin Yang, Yu Liu, Benjamin Soibam
BACKGROUND: Comprehensive understanding of intratumor heterogeneity requires identification of molecular markers, which are capable of differentiating different subpopulations and which also have clinical significance. One important tool that has been addressing this issue is single cell RNA-Sequencing (scRNASeq) that allows the quantification of expression profiles of transcripts in individual cells in a population of cancer cells. Using the expression profiles from scRNASeq, current studies conduct analysis to group cells into different subpopulations using clustering algorithms...
February 13, 2018: BMC Genomics
Suhn Kyong Rhie, Lijun Yao, Zhifei Luo, Heather Witt, Shannon Schreiner, Yu Guo, Andrew A Perez, Peggy J Farnham
High expression of the transcription factor ZFX is correlated with proliferation, tumorigenesis, and patient survival in multiple types of human cancers. However, the mechanism by which ZFX influences transcriptional regulation has not been determined. We performed ChIP-seq in four cancer cell lines (representing kidney, colon, prostate, and breast cancers) to identify ZFX binding sites throughout the human genome. We identified ~9,000 ZFX binding sites and found that the majority of the sites are in CpG island promoters...
February 2, 2018: Genome Research
Peng Ye, Yu Shi, Nairui An, Qian Zhou, Juan Guo, Xinghua Long
Cumulative evidence has associated microRNA (miRNA) with cancer development, and among those miRNAs, miR-145 has been identified as an anti-oncomiRNA. However, the comprehensive mechanisms of action of miR-145 in breast cancer development have not yet been fully elucidated. Herein, we performed next-generation sequencing to detect the expression profiles of the transcriptome and conducted cellular function experiments after miR-145 overexpression. The results verified the inhibitory effects of miR-145 on breast cancer cell proliferation, colony formation, migration and invasion...
February 6, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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