VIRMA-dependent N6-methyladenosine modifications regulate the expression of long non-coding RNAs CCAT1 and CCAT2 in prostate cancer

RNA methylation at position N6 in adenosine (m6A) and its associated methyltransferase complex (MTC) are involved in tumorigenesis. We aimed to explore m6A biological function for long non-coding RNAs (lncRNAs) in prostate cancer (PCa) and its clinical significance. m6A and MTC levels in PCa cells were characterized by ELISA and western blot. Putative m6A-regulated lncRNAs were identified and validated by lncRNA profiler qPCR array and bioinformatics analysis, followed by m6A/RNA co-immunoprecipitation. Impact of m6A depletion on RNA stability was assessed by Actinomycin D assay. The association of m6A-levels with PCa prognosis was examined in clinical samples. Higher m6A-levels and VIRMA overexpression were detected in metastatic castration-resistant PCa (mCRPC) cells (p < 0.05). VIRMA knockdown in PC-3 cells significantly decreased m6A-levels (p = 0.0317), attenuated malignant phenotype and suppressed the expression of oncogenic lncRNAs CCAT1 and CCAT2 (p < 0.00001). VIRMA depletion and m6A reduction decreased the stability and abundance of CCAT1/2 transcripts. Higher expression of VIRMA, CCAT1, and CCAT2 as a group variable was an independent predictor of poor prognosis (HR = 9.083, CI95% 1.911–43.183, p = 0.006). VIRMA is a critical factor sustaining m6A-levels in PCa cells. VIRMA downregulation attenuates the aggressive phenotype of PCa by overall reduction of m6A-levels decreasing stability and abundance of oncogenic lncRNAs

Assessing contamination from maritime trade and transportation on Iberian waters: Impact on Mytilus sp

Contamination derived from maritime transportation is not only linked to petroleum-based substances but also to transportation of other substances such as hazardous and noxious nature (HNS). Over the last decade, the maritime trade of HNS has been augmenting. However, levels of HNS in aquatic environment are still quite unknown. So, an integrative study, combining a chemical and a multi-biomarker evaluation, was done in the NW Atlantic Iberian coast where specimens of Mytilus sp. were collected. Ten HNS were found in the digestive gland of mussels from Vila Ch˜a and Foz, though at generally low levels. Only measurable levels of benzene, trichloroethylene and 1,1,2-trichlorethane were found in other locations. Principal component analysis produced a clear distinction between Vila Ch˜a and Foz and the remaining sampling sites. Biomarkers associated to contamination were the levels of lipid peroxidation (LPO) and activity of glutathione reductase (GR), superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes. Correlations between biomarkers and HNS levels highlight the importance of performing biomonitoring campaigns integrating chemical analysis and a biomarker approach to accurately assess the environmental state of aquatic environments

Assessing contamination from maritime trade and transportation on Iberian waters: Impact on Platichthys flesus

Maritime trade and transportation of hazardous and noxious substances (HNS) have been increasing in European waters, augmenting the risk of accidental spills from ships or in harbours. Despite their reported toxicity and hazardousness, information on HNS levels in the aquatic environment is still lacking. Therefore, an assessment combining a chemical and a multi-biomarker evaluation on HNS contamination was done in NW Iberian estuaries of Rivers Minho, Lima and Douro using Platichthys flesus (flounder). Of the twenty-five HNS measured, fifteen were found in flounder liver and muscle, and a few in sediments, though at generally low levels. Principal component analysis produced a clear distinction among sites, with Douro River estuary arising as the most impacted. Oxidised proteins and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were the biomarkers contributing to site discrimination. Correlations between biomarkers and HNS levels provided important baseline information for the study area and potential biological effects of HNS on this sentinel species

Data for the analysis of interactive multibiomarker responses of a marine crustacean to long-term exposure to aquatic contaminants

The data presented herein relates to the article entitled “Multibiomarker interactions to diagnose and follow-up chronic exposure of a marine crustacean to hazardous and noxious substances (HNS)” (Abreu et al., 2018). Multibiomarker approaches, including molecular, biochemical, physiological and behaviour parameters, are recognised as valuable and cost-effective to employ in integrated chemical and biological effects monitoring of aquatic contamination. Many biomarkers assessed in such programmes share common physiological pathways, showing concomitant or interdependent responses, which can reflect in increased energy costs related to physiological acclimation. Though, routine single biomarker data analysis, and exploratory principal component analysis, limit information obtained from the data collected and their functional interpretation. Ultimately, this influences the type of management actions taken to protect an affected ecosystem. This article presents data employed to develop an analytical approach accounting for multibiomarker interactions. The method was useful to diagnose and follow-up long-term exposure of the marine green crab (Carcinus maenas) to Hazardous and Noxious Substances (HNS)

Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm

TGCTs represent a model of curable disease afflicting especially young men. Defining tumor biological characteristics is crucial to increase current knowledge and tailor the best clinical management. Ki67, a potential prognostic marker, still exhibits heterogenous associations with patient outcomes, thus bringing the need of corroboration with larger cohorts in clinical practice. LSD1, an epigenetic enzyme, represents a future target for epigenetic drugs that may lower treatment-associated morbidity. This study aimed to assess Ki67/LSD1 immunoexpression across all TGCT histological subtypes and correlate it with clinicopathological features. Results were compared with an in silico analysis of the TCGA database. Immunohistochemistry for Ki67 and LSD1 was carried out in a cohort of 157 TGCT tumor samples and assessed using a digital pathology algorithm. LSD1 protein expression was explored in TGCT cell lines, including ATRA-differentiated clones. There was a significant positive correlation between Ki67 and LSD1 H-scores (rs = 0.182, p = 0.037). Ki67 positivity percentage and H-score were significantly higher in non-seminomas (p = 0.0316 and 0.0113, respectively). Expression was not significantly different according to clinicopathological features, including stage, IGCCCG prognosis-based system, or relapse/progression-free survival, which was corroborated by in silico analysis. Our study, making use of digital image analysis, does not confirm the utility of these biomarkers in a daily practice cohort. Although not affecting patient outcome in our cohort, LSD1 is expressed overall in TGCTs, suggesting sensitivity to LSD1 inhibitors

The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound

Simplified schematic overview of the function of the major organs involved in lipid homeostasis.

<p>The liver has a central role in the synthesis, metabolism and distribution of glucose and fatty acids. The adipose tissue is the principal site of excess energy storage in the form of fat (triglycerides) and liberates fatty acids upon demand. The muscle is the major site of lipid oxidation and energy expenditure. The brain acts as a lipid sensor; it receives signals from the other organs to adjust energy homeostasis by changing behaviour (e.g. food intake and expenditure). When energy consumption exceeds expenditure excess triglycerides are stored not only in adipose tissue but in muscle and liver as well, leading to metabolic disorders [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143911#pone.0143911.ref048" target="_blank">48</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143911#pone.0143911.ref049" target="_blank">49</a>].</p

Morphological parameters of male and female zebrafish following chronic waterborne exposure (9 months) to tributyltin (TBT).

<p>Values are mean±SEM (n = 15); CF and HSI are the condition factor and hepatosomatic index, respectively; **<i>p</i><0.05 and *<0.1 (compared to solvent control; one-way ANOVA followed by Dunnett's test)</p

Boletín de Segovia: Número 147 - 1886 diciembre 8

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 200

TBT <i>in vivo</i> induction of lipogenic genes in the brain.

<p>qRT-PCR analysis of selected lipogenic transcription factors and metabolizing enzymes in the brain of (A) male, and (B) female zebrafish following chronic exposure (9 months) to waterborne 10 and 50 ng/L of TBT (as Sn). Values were normalized to β-actin and expressed as the average fold changes ± SEM (n = 7) of the solvent control group. **<i>p<</i>0.05 and *<i>p</i><0.1 compared to solvent control (one-way ANOVA, followed by Dunnett’s test).</p