miR-223 inhibits dengue virus replication by negatively regulating the microtubule-destabilizing protein STMN1 in EAhy926 cells
MICROBES AND INFECTION
Authors: Wu, Na; Gao, Na; Fan, Dongying; Wei, Jianchun; Zhang, Jing; An, Jing
Abstract
The pathogenesis of dengue virus (DENY) infection is not completely understood. Endothelial cells may act as a target of the virus and be involved in disease pathogenesis. Therefore, the identification of host cell components involved in DENY replication would provide useful information for better understanding DENY infection. In this study, a significantly decreased level of miR-223 was found in DENV2-infected EAhy926 cells, a human endothelial-like cell line, whereas miR-223 overexpression inhibited DENV2 replication. Furthermore, we identified that miR-223 directly targeted the 3' untranslated region (3'UTR) of the messenger RNA (mRNA) for microtubule-destabilizing protein stathmin 1 (STMN1), thereby reducing its mRNA and protein levels. The depletion of miR-223 or overexpression of STMN1 enhanced DENV2 replication, whereas the opposite (increased miR-223 or decreased STMN1) suppressed DENV2 replication, indicating that miR-223 down-regulates STMN1 expression by targeting the 3'UTR of the STMN1 gene to inhibit DENV2 replication. Finally, we demonstrated that two transcription factors, C/EBP alpha and E2F1, are involved in the regulation of miR-223 levels after DENV2 infection in EAhy926 cells. Collectively, our results suggest that miR-223 may act as a novel antiviral factor, which may open an avenue to limit DENY infection. (C) 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Stathmin genotype is associated with reexperiencing symptoms of posttraumatic stress disorder in Chinese earthquake survivors
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Authors: Cao, Chengqi; Wang, Li; Wang, Richu; Dong, Chongya; Qing, Yulan; Zhang, Xiangyang; Zhang, Jianxin
Abstract
Stathmin (STMN1) has been demonstrated as a regulator of fear processing across species, which implicates that it may be important in the etiopathogenesis of fear-related psychiatric disorders such as posttraumatic stress disorder (PTSD). This study examined the association between STMN1 rs182455 genotype, a single nucleotide polymorphism (SNP) located within or close to the putative transcriptional control region of STMN1 gene, and PTSD symptoms. A total of 326 Chinese adults who suffered from a deadly 2008 Wenchuan earthquake and unexpectedly lost their children during the disaster participated in this study. PTSD symptoms were measured with the PTSD Checklist (PCL). The Sequenom iPlex chemistries and the MassARRAY system were used to genotype the STMN1 rs182455 SNP. Our results indicated that the STMN1rs182455 genotype was not associated with severity of total PTSD symptoms in either females or males; however, it could significantly predict severity of PTSD's reexperiencing symptoms in females. The findings provide preliminary evidence supporting the important role of STMN1 in the development of PTSD, and expand extant knowledge on the genetic underpinnings of PTSD and the sex-specific expression of PTSD's symptoms. (C) 2013 Elsevier Inc. All rights reserved.