20 de outubro de 2018

"Tracking EBV-encoded RNAs (EBERs) from the nucleus to the excreted exosomes of B-lymphocytes."

Related Articles

Tracking EBV-encoded RNAs (EBERs) from the nucleus to the excreted exosomes of B-lymphocytes.

Sci Rep. 2018 Oct 18;8(1):15438

Authors: Ahmed W, Tariq S, Khan G

Abstract
Epstein-Barr virus-encoded RNAs (EBER1 and EBER2) are two highly abundant, non-protein coding RNAs consistently expressed in all EBV infected cells, but their function remains poorly understood. Conventional in situ hybridization studies have indicated that these RNAs are present exclusively in the nucleus. We have recently demonstrated that EBERs can be excreted from infected cells via exosomes. However, the details of the steps involved in their excretion remain unknown. In this study, we aimed to directly track the journey of EBERs from the nucleus to the excretory exosomes of EBV immortalized B-lymphocytes. Using a combination of molecular and novel immuno-gold labelled electron microscopy (EM) based techniques, we demonstrate the presence of EBERs, not only in the nucleus, but also in the cytoplasm of EBV infected B cell lines. EBERs were also seen in exosomes shed from infected cells along with the EBER binding protein La. Our results show, for the first time, that at least a proportion of EBERs are transported from the nucleus to the cytoplasm where they appear to be loaded into multi-vesicular bodies for eventual excretion via exosomes.

PMID: 30337610 [PubMed - in process]



https://www.ncbi.nlm.nih.gov/pubmed/30337610?dopt=Abstract
October 20, 2018 at 10:05AM

19 de outubro de 2018

"Overexpression of cellular telomerase RNA enhances virus-induced cancer formation"


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https://www.nature.com/articles/s41388-018-0544-1
October 19, 2018 at 11:31AM

18 de outubro de 2018

"Zebrafish: Speeding Up the Cancer Drug Discovery Process."

Related Articles

Zebrafish: Speeding Up the Cancer Drug Discovery Process.

Cancer Res. 2018 Oct 16;:

Authors: Letrado P, de Miguel I, Lamberto I, Díez-Martínez R, Oyarzabal J

Abstract
Zebrafish (Danio rerio) is an ideal in vivo model to study a wide variety of human cancer types. In this review, we provide a comprehensive overview of zebrafish in the cancer drug discovery process, from (i) approaches to induce malignant tumors, (ii) techniques to monitor cancer progression, and (iii) strategies for compound administration to (iv) a compilation of the 355 existing case studies showing the impact of zebrafish models on cancer drug discovery, which cover a broad scope of scenarios. Finally, based on the current state-of-the-art analysis, this review presents some highlights about future directions using zebrafish in cancer drug discovery and the potential of this model as a prognostic tool in prospective clinical studies. Cancer Res; 78(21); 1-11. ©2018 AACR.

PMID: 30327381 [PubMed - as supplied by publisher]



https://www.ncbi.nlm.nih.gov/pubmed/30327381?dopt=Abstract
October 18, 2018 at 12:50PM

17 de outubro de 2018

"EBV reduces autophagy, intracellular ROS and mitochondria to impair monocyte survival and differentiation."

Related Articles

EBV reduces autophagy, intracellular ROS and mitochondria to impair monocyte survival and differentiation.

Autophagy. 2018 Oct 16;:

Authors: Gilardini Montani MS, Santarelli R, Granato M, Gonnella R, Torrisi MR, Faggioni A, Cirone M

Abstract
EBV has been reported to impair monocyte in vitro differentiation into dendritic cells (DCs) and reduce cell survival. In this study, we added another layer of knowledge to this topic and showed that these effects correlated with macroautophagy/autophagy, ROS and mitochondrial biogenesis reduction. Of note, autophagy and ROS, although strongly interconnected, have been separately reported to be induced by CSF2/GM-CSF (colony stimulating factor 2) and required for CSF2-IL4-driven monocyte in vitro differentiation into DCs. We show that EBV infects monocytes and initiates a feedback loop in which, by inhibiting autophagy, reduces ROS and through ROS reduction negatively influences autophagy. Mechanistically, autophagy reduction correlated with the downregulation of RAB7 and ATG5 expression and STAT3 activation, leading to the accumulation of SQSTM1/p62. The latter activated the SQSTM1-KEAP1- NFE2L2 axis and upregulated the anti-oxidant response, reducing ROS and further inhibiting autophagy. ROS decrease correlated also with the reduction of mitochondria, the main source of intracellular ROS, achieved by the downregulation of NRF1 and TFAM, mitochondrial biogenesis transcription factors. Interestingly, mitochondria supply membranes and ATP required for autophagy execution, thus their reduction may further reduce autophagy in EBV-infected monocytes. In conclusion, this study shows for the first time that the interconnected reduction of autophagy, intracellular ROS and mitochondria mediated by EBV switches monocyte differentiation into apoptosis, giving new insights into the mechanisms through which this virus reduces immune surveillance.

PMID: 30324853 [PubMed - as supplied by publisher]



https://www.ncbi.nlm.nih.gov/pubmed/30324853?dopt=Abstract
October 17, 2018 at 08:51AM