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cancer transcriptome

Jiyu Tong, Richard A Flavell, Hua-Bing Li
N6 -methyladenosine (m6 A) is the most common post-transcriptional RNA modification throughout the transcriptome, affecting fundamental aspects of RNA metabolism. m6 A modification could be installed by m6 A "writers" composed of core catalytic components (METTL3/METTL14/WTAP) and newly defined regulators and removed by m6 A "erasers" (FTO and ALKBH5). The function of m6 A is executed by m6 A "readers" that bind to m6 A directly (YTH domain-containing proteins, eIF3 and IGF2BPs) or indirectly (HNRNPA2B1)...
August 10, 2018: Frontiers of Medicine
Feng Li, Janice M Yoshizawa, Kyoung-Mee Kim, Julie Kanjanapangka, Tristan R Grogan, Xiaoyan Wang, David E Elashoff, Shigeo Ishikawa, David Chia, Wei Liao, David Akin, Xinmin Yan, Min-Sun Lee, Rayun Choi, Su-Mi Kim, So-Young Kang, Jae-Moon Bae, Tae-Sung Sohn, Jun-Ho Lee, Min-Gew Choi, Byung-Hoon Min, Jun-Haeng Lee, Jae J Kim, Yong Kim, Sung Kim, David T W Wong
BACKGROUND: Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC. METHODS: Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR)...
August 10, 2018: Clinical Chemistry
Agnese Po, Luana Abballe, Claudia Sabato, Francesca Gianno, Martina Chiacchiarini, Giuseppina Catanzaro, Enrico De Smaele, Felice Giangaspero, Elisabetta Ferretti, Evelina Miele, Zein Mersini Besharat
Molecular classification has improved the knowledge of medulloblastoma (MB), the most common malignant brain tumour in children, however current treatments cause severe side effects in patients. Cancer stem cells (CSCs) have been described in MB and represent a sub population characterised by self-renewal and the ability to generate tumour cells, thus representing the reservoir of the tumour. To investigate molecular pathways that characterise this sub population, we isolated CSCs from Sonic Hedgehog Medulloblastoma (SHH MB) arisen in Patched 1 ( Ptch1 ) heterozygous mice, and performed miRNA- and mRNA-sequencing...
August 8, 2018: International Journal of Molecular Sciences
Ke Su, Qian Zhao, Aiping Bian, Chunfang Wang, Yujie Cai, Yanyan Zhang
Long noncoding RNAs (lncRNAs), a novel class of transcripts that have critical roles in carcinogenesis and progression, have emerged as important gene expression modulators. However, the pathophysiological contributions and the underlying mechanisms of specific lncRNAs in cervical cancer remain largely unknown. Here, using transcriptome microarray analysis, we identified a novel lncRNA termed lncRNA upregulated in cervical cancer (lnc-UICC) that was highly expressed in cervical cancer tissue. lnc-UICC expression in cervical cancer was associated with FIGO stage, lymph node metastasis and prognosis...
2018: American Journal of Cancer Research
Andrew J Annalora, Shawn O'Neil, Jeremy D Bushman, James E Summerton, Craig B Marcus, Patrick L Iversen
Ewing's sarcoma treatment failures are associated with high mortality indicating a need for new therapeutic approaches. We used a k-mer counting approach to identify cancer-specific mRNA transcripts in 3 Ewing's Family Tumor (EFT) cell lines not found in the normal human transcriptome. Phosphorodiamidate morpholino oligomers targeting six EFT-specific transcripts were evaluated for cytotoxicity in TC-32 and CHLA-10 EFT lines and in HEK293 renal epithelial control cells. Average morpholino efficacy (EC50 ) was 0...
July 17, 2018: Oncotarget
Derek Wong, Kohl Lounsbury, Amy Lum, Jungeun Song, Susanna Chan, Veronique LeBlanc, Suganthi Chittaranjan, Marco Marra, Stephen Yip
Aberrations in Capicua (CIC) have recently been implicated as a negative prognostic factor in a multitude of cancer types through activation of the MAPK signalling cascade and derepression of oncogenic ETS transcription factors. The Ataxin-family protein ATXN1L has previously been reported to interact with CIC in developmental and disease contexts to facilitate the repression of CIC target genes. To further investigate this relationship, we performed functional in vitro studies utilizing ATXN1LKO and CICKO human cell lines and characterized a reciprocal functional relationship between CIC and ATXN1L...
August 9, 2018: Oncogene
Matthew D Young, Thomas J Mitchell, Felipe A Vieira Braga, Maxine G B Tran, Benjamin J Stewart, John R Ferdinand, Grace Collord, Rachel A Botting, Dorin-Mirel Popescu, Kevin W Loudon, Roser Vento-Tormo, Emily Stephenson, Alex Cagan, Sarah J Farndon, Martin Del Castillo Velasco-Herrera, Charlotte Guzzo, Nathan Richoz, Lira Mamanova, Tevita Aho, James N Armitage, Antony C P Riddick, Imran Mushtaq, Stephen Farrell, Dyanne Rampling, James Nicholson, Andrew Filby, Johanna Burge, Steven Lisgo, Patrick H Maxwell, Susan Lindsay, Anne Y Warren, Grant D Stewart, Neil Sebire, Nicholas Coleman, Muzlifah Haniffa, Sarah A Teichmann, Menna Clatworthy, Sam Behjati
Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell...
August 10, 2018: Science
Ayako Ohara, Yasuhiko Takahashi, Miwa Kondo, Yu Okuda, Shuji Takeda, Masahiko Kushida, Kentaro Kobayashi, Kayo Sumida, Tomoya Yamada
Phenobarbital (PB) is a nongenotoxic hepatocellular carcinogen in rodents. PB induces hepatocellular tumors by activating the constitutive androstane receptor (CAR). Some previous research has suggested the possible involvement of epigenetic regulation in PB-promoted hepatocellular tumorigenesis, but the details of its molecular mechanism are not fully understood. In the present study, comprehensive analyses of DNA methylation, hydroxymethylation and gene expression using microarrays were performed in mouse hepatocellular adenomas induced by a single 90 mg kg-1 intraperitoneal injection dose of diethylnitrosamine (DEN) followed by 500 ppm PB in the diet for 27 weeks...
November 1, 2017: Toxicology Research
Ageliki Laina, Aikaterini Gatsiou, Georgios Georgiopoulos, Kimon Stamatelopoulos, Konstantinos Stellos
Since our knowledge on structure and function of messenger RNA (mRNA) has expanded from merely being an intermediate molecule between DNA and proteins to the notion that RNA is a dynamic gene regulator that can be modified and edited, RNA has become a focus of interest into developing novel therapeutic schemes. Therapeutic modulation of RNA molecules by DNA- and RNA-based therapies has broadened the scope of therapeutic targets in infectious diseases, cancer, neurodegenerative diseases and most recently in cardiovascular diseases as well...
2018: Frontiers in Physiology
Byungjin Hwang, Ji Hyun Lee, Duhee Bang
Rapid progress in the development of next-generation sequencing (NGS) technologies in recent years has provided many valuable insights into complex biological systems, ranging from cancer genomics to diverse microbial communities. NGS-based technologies for genomics, transcriptomics, and epigenomics are now increasingly focused on the characterization of individual cells. These single-cell analyses will allow researchers to uncover new and potentially unexpected biological discoveries relative to traditional profiling methods that assess bulk populations...
August 7, 2018: Experimental & Molecular Medicine
Rajshekhar R Giraddi, Chi-Yeh Chung, Richard E Heinz, Ozlen Balcioglu, Mark Novotny, Christy L Trejo, Christopher Dravis, Berhane M Hagos, Elnaz Mirzaei Mehrabad, Luo Wei Rodewald, Jae Y Hwang, Cheng Fan, Roger Lasken, Katherine E Varley, Charles M Perou, Geoffrey M Wahl, Benjamin T Spike
The mammary gland consists of cells with gene expression patterns reflecting their cellular origins, function, and spatiotemporal context. However, knowledge of developmental kinetics and mechanisms of lineage specification is lacking. We address this significant knowledge gap by generating a single-cell transcriptome atlas encompassing embryonic, postnatal, and adult mouse mammary development. From these data, we map the chronology of transcriptionally and epigenetically distinct cell states and distinguish fetal mammary stem cells (fMaSCs) from their precursors and progeny...
August 7, 2018: Cell Reports
W L Allen, P D Dunne, S McDade, E Scanlon, M Loughrey, H Coleman, C McCann, K McLaughlin, Z Nemeth, N Syed, P Jithesh, K Arthur, R Wilson, V Coyle, D McArt, G I Murray, L Samuel, P Nuciforo, J Jimenez, G Argiles, R Dienstmann, J Tabernero, L Messerini, S Nobili, E Mini, K Sheahan, E Ryan, P G Johnston, S Van Schaeybroeck, M Lawler, D B Longley
Purpose: Transcriptomic profiling of colorectal cancer (CRC) has led to identification of four consensus molecular subtypes (CMS1-4), which have prognostic value in stage II/III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system has helped to define the biology specific to the epithelial component of colorectal tumors. However, the clinical value of these classifications in predicting response to standard-of-care adjuvant chemotherapy remains unknown...
June 13, 2018: JCO precision oncology
Lisett Contreras, Ruben I Calderon, Armando Varela-Ramirez, Hong-Yu Zhang, Yuan Quan, Umashankar Das, Jonathan R Dimmock, Rachid Skouta, Renato J Aguilera
PURPOSE: Previously, compounds containing a piperidone structure have been shown to be highly cytotoxic to cancer cells. Recently, we found that the piperidone compound P2 exhibits a potent anti-neoplastic activity against human breast cancer-derived cells. Here, we aimed to evaluate two piperidone compounds, P1 and P2, for their potential anti-neoplastic activity against human leukemia/lymphoma-derived cells. METHODS: Cytotoxicity and apoptosis induction were evaluated using MTS, annexin V-FITC/PI and mitochondrial membrane potential polychromatic assays to confirm the mode of action of the piperidone compounds...
August 7, 2018: Cellular Oncology (Dordrecht)
Hongshun Shi, Hui Li, Ronghua Yuan, Wen Guan, Xiaomei Zhang, Shaoyang Zhang, Wenliang Zhang, Fang Tong, Li Li, Zhihong Song, Changwei Wang, Shulan Yang, Haihe Wang
BACKGROUND: Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive. METHODS: We performed a transcriptome-wide screen to identify novel bounding mRNA of PCBP1. The bind regions between PCBP1 with target mRNA were investigated by using point mutation and luciferase assay...
August 7, 2018: Journal of Experimental & Clinical Cancer Research: CR
John P Rooney, Brian Chorley, Nicole Kleinstreuer, J Christopher Corton
High-throughput transcriptomic (HTTr) technologies are increasingly being used to screen environmental chemicals in vitro to identify molecular targets and provide mechanistic context for regulatory testing. Here, we describe the development and validation of a novel gene expression biomarker to identify AR-modulating chemicals using a pattern matching method. AR biomarker genes were identified by their consistent expression after exposure to 4‚ÄČAR agonists and 4‚ÄČAR antagonists and included only those genes that were regulated by AR...
July 31, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Matthew P Salomon, Xiaowen Wang, Diego M Marzese, Sandy C Hsu, Nellie Nelson, Xin Zhang, Chikako Matsuba, Yuki Takasumi, Carmen Ballesteros-Merino, Bernard A Fox, Garni Barkhoudarian, Daniel F Kelly, Dave S B Hoon
Purpose: Pituitary adenomas are one of the most common benign neoplasms of the central nervous system. Although emerging evidence suggests roles for both genetic and epigenetic factors in tumorigenesis, the degree to which these factors contribute to disease remains poorly understood. Experimental Design: A multiplatform analysis was performed to identify the genomic and epigenomic underpinnings of disease among the three major subtypes of surgically resected pituitary adenomas in 48 patients: growth hormone (GH)-secreting ( n = 17), adrenocorticotropic hormone (ACTH)-secreting ( n = 13, including 3 silent-ACTH adenomas), and endocrine-inactive ( n = 18)...
July 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Julia S Barthold, Richard Ivell
Nonsyndromic cryptorchidism is a common multifactorial, condition with long-term risks of subfertility and testicular cancer. Revealing the causes of cryptorchidism will likely improve prediction and prevention of adverse outcomes. Herein we provide our current perspective of cryptorchidism complexity in a synthesis of cumulative clinical and translational data generated by ourselves and others. From our recent comparison of genome-wide association study (GWAS) data of cryptorchidism with or without testicular germ cell tumor, we identified RBFOX family genes as candidate susceptibility loci...
2018: Frontiers in Endocrinology
Nathan Ungerleider, Monica Concha, Zhen Lin, Claire Roberts, Xia Wang, Subing Cao, Melody Baddoo, Walter N Moss, Yi Yu, Michael Seddon, Terri Lehman, Scott Tibbetts, Rolf Renne, Yan Dong, Erik K Flemington
Our appreciation for the extent of Epstein Barr virus (EBV) transcriptome complexity continues to grow through findings of EBV encoded microRNAs, new long non-coding RNAs as well as the more recent discovery of over a hundred new polyadenylated lytic transcripts. Here we report an additional layer to the EBV transcriptome through the identification of a repertoire of latent and lytic viral circular RNAs. Utilizing RNase R-sequencing with cell models representing latency types I, II, and III, we identified EBV encoded circular RNAs expressed from the latency Cp promoter involving backsplicing from the W1 and W2 exons to the C1 exon, from the EBNA BamHI U fragment exon, and from the latency long non-coding RPMS1 locus...
August 6, 2018: PLoS Pathogens
Lusy Handoko, Bogumil Kaczkowski, Chung-Chau Hon, Marina Lizio, Masatoshi Wakamori, Takayoshi Matsuda, Takuhiro Ito, Prashanti Jeyamohan, Yuko Sato, Kensaku Sakamoto, Shigeyuki Yokoyama, Hiroshi Kimura, Aki Minoda, Takashi Umehara
The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23...
August 6, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Pang-Kuo Lo, Qun Zhou
Epigenomics encompasses studies of the chemical modifications of genomic DNA and associated histones, interactions between genomic DNA sequences and proteins, the dynamics of the chromosomal conformation, the functional relationships between these epigenetic events, and the regulatory impacts of these epigenetic events on gene expression in cells. In comparison to current techniques that are only capable of characterizing average epigenomic features across bulk cell ensembles, single-cell epigenomic methodologies are emerging as powerful new techniques to study cellular plasticity and heterogeneity, as seen in stem cells and cancer...
2018: Journal of clinical genomics
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