Sexual differentiation in zebrafish is complex. Although zebrafish sex determination is primarily genetic, hormonal and environmental factors can influence sexual development. 17 alpha-methyltestosterone (MT), a synthetic androgen, induces female-to-male sex reversal in zebrafish. MT treatment is routinely used in aquaculture for production of all-male populations. However, the molecular mechanisms underlying 17 alpha-methyltestosterone induced gonad masculinisation in fish are poorly understood.In this study, we analysed gonad transcriptomes of zebrafish treated with 17 alpha-methyltestosterone during gonadal development (from 20 dpf to 40 dpf and 60 dpf) and compared them with testis and ovary transcriptomes of untreated zebrafish. These data improve our understanding of the role of androgens in teleost sex differentiation.
Histological and transcriptomic effects of 17α-methyltestosterone on zebrafish gonad development.
No sample metadata fields
View SamplesAcquisition of a new strain of non-typeable Haemophilus influenzae (NTHi) is often associated with exacerbation of chronic obstructive pulmonary disease (COPD). We have previously reported that COPD patients who are homozygous null for SIGLEC14 gene is less susceptible to COPD exacerbation than those who have wild-type allele with functional SIGLEC14 gene.
Association of serum interleukin-27 with the exacerbation of chronic obstructive pulmonary disease.
Cell line
View SamplesGenome-wide studies have identified abundant small, non-coding RNAs including snRNAs, snoRNAs, cryptic unstable transcripts (CUTs), and upstream regulatory RNAs (uRNAs) that are transcribed by RNA polymerase II (pol II) and terminated by a Nrd1-dependent pathway. Here, we show that the prolyl isomerase, Ess1, is required for Nrd1-dependent termination of ncRNAs. Ess1 binds the carboxy terminal domain (CTD) of pol II and is thought to regulate transcription by conformational isomerization of Ser-Pro bonds within the CTD. In ess1 mutants, expression of ~10% of the genome was altered, due primarily to defects in termination of snoRNAs, CUTs, SUTs and uRNAs. Ess1 promoted dephosphorylation of Ser5 (but not Ser2) within the CTD, most likely by the Ssu72 phosphatase, and we provide evidence for a competition between Nrd1 and Pcf11 for CTD-binding that is regulated by Ess1-dependent isomerization. This is the first example of a prolyl isomerase required for interpreting the CTD code.
The Ess1 prolyl isomerase is required for transcription termination of small noncoding RNAs via the Nrd1 pathway.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence.
Sex, Age, Specimen part
View SamplesIntroduction: The majority of pulmonary carcinoid (PC) tumors can be cured by surgical resection alone, but a significant proportion of patients experience recurrences. PC is insensitive to conventional chemotherapy, and it would be necessary to reveal the molecular mechanisms of metastasis and develop targeted therapeutics.
Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence.
Sex, Age, Specimen part
View SamplesNon-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitor. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752-resistant EBC1 cells, namely EBC1-R cells. EBC1-R cells showed overexpression of ATP-binding cassette sub-family B member 1 (ABCB1) as well as phosphorylation of MET. EBC1-R cells grew as cell spheres that exhibited cancer stem cell-like (CSC) properties and epithelial mesenchymal transition (EMT). The levels of two miRNAs, miR-374a and miR-138 which targeted ABCB1, were decreased in EBC1-R cells. ABCB1 siRNA and ABCB1 inhibitor elacridar could reduce sphere numbers and suppress EMT. Elacridar could also reverse the resistance to PHA-665752 in EBC1-R cells. Our study demonstrated that ABCB1 overexpression which was associated with CSC properties and EMT was involved in the acquired resistance to MET inhibitor. Inhibition of ABCB1 might be a novel therapeutic strategy for NSCLC patients with acquired resistance to MET inhibitor.
Inhibition of ABCB1 Overcomes Cancer Stem Cell-like Properties and Acquired Resistance to MET Inhibitors in Non-Small Cell Lung Cancer.
Cell line
View SamplesIn order to ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the anti-tumour effects of Trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via MTT assay. TSA and vorinostat both displayed strong anti-tumor activities in a proportion of NSCLC cell lines, and suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.0001).
Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model.
No sample metadata fields
View SamplesAnticancer drug clustering in lung cancer based on gene expression profiles.
Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database.
No sample metadata fields
View SamplesAn essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,918 protein-coding promoters and 17,918 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, hundreds of promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements is regulated during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing. Overall design: Capped nuclear RNA-seq of wild-type and glp-1 was performed to monitor transcription elongation across C. elegans development and ageing. Two biological replicates were done for each time point (six developmental stages and five ageing timepoints).
Chromatin accessibility dynamics across <i>C. elegans</i> development and ageing.
Cell line, Subject
View SamplesOne hundred and seven lung Squamous Cell Carcinomas collected from early stage (stage I+II; AJCC 7th edition) patients at the National Cancer Center Hospital (Tokyo, Japan) between 1997 and 2008 were hybridized to the Human Transcriptome (HT) Array 2.0
A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts.
Sex, Age, Specimen part
View Samples