RT Journal Article
T1 Regulation of TFPIα expression by miR-27a/b-3p in human endothelial cells under normal conditions and in response to androgens.
A1 B Arroyo, Ana
A1 Salloum-Asfar, Salam
A1 Perez-Sanchez, Carlos
A1 Teruel-Montoya, Raul
A1 Navarro, Silvia
A1 Garcia-Barbera, Nuria
A1 Luengo-Gil, Gines
A1 Roldan, Vanessa
A1 Hansen, John-Bjarne
A1 Lopez-Pedrera, Chary
A1 Vicente, Vicente
A1 Gonzalez-Conejero, Rocio
A1 Martinez, Constantino
AB The increased risk of cardiovascular events in older men is multifactorial, but the significant reduction of testosterone levels has been involved. As this hormone regulates the expression of TFPI by unknown mechanisms, we aimed to evaluate the role of miRNAs in the regulation of TFPIα expression under normal conditions and in response to androgens. In silico studies allowed the selection of 4 miRNAs as potential TFPIα regulators. Only miR-27a/b-3p significantly reduced TFPIα expression in two endothelial cell lines. Luciferase assays demonstrated a direct interaction between miR-27a/b-3p and TFPI 3'UTR. Ex vivo analysis of TFPI and miRNA levels in 74 HUVEC samples from healthy subjects, showed a significant and inverse correlation between TFPI and miR-27a-3p. Moreover, anticoagulant activity of TFPIα from cells supernatants decreased ~30% with miR-27a/b-3p and increased ~50% with anti-miR-27a/b-3p. Interestingly, treatment of EA.hy926 with a physiological dose of dihydrotestosterone (30 nM) significantly increased (~40%) TFPIα expression with a parallel decreased (~50%) of miR-27a/b-3p expression. In concordance, increased levels of miR-27a/b-3p normalized the up-regulation induced by testosterone. Our results suggest that testosterone is a hinge in miR-27/TFPIα regulation axis. Future studies are needed to investigate whether testosterone variations are involved in a miR-27/TFPIα dysregulation that could increase the cardiovascular risk.
PB Nature Publishing Group
YR 2017
FD 2017-01-26
LK http://hdl.handle.net/10668/10906
UL http://hdl.handle.net/10668/10906
LA en
NO B Arroyo A, Salloum-Asfar S, Pérez-Sánchez C, Teruel-Montoya R, Navarro S, García-Barberá N, et al. Regulation of TFPIα expression by miR-27a/b-3p in human endothelial cells under normal conditions and in response to androgens. Sci Rep. 2017 Feb 27;7:43500
NO The authors thank Dr Renato Baserga, Department of Cancer Biology, Thomas Jefferson University, for kindly providing us HCT116-Dicer KO cells. The authors thank Javier Corral for reviewing the paper and María del MarSánchez Vera for technical expertise. This work was supported by research grants from the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) [PI14/00253, Red RIC (RD12/0042/0050)], and19873/GERM/15 (Fundación Séneca). A.B.A. has a research Fellowship from University of Murcia. C.M. is an investigator from the Fundación para la Formación e Investigación Sanitarias de la Región de Murcia (FFIS).
DS RISalud
RD Apr 19, 2025