| Title |
miR-133a Regulates Vitamin K 2,3-Epoxide Reductase Complex Subunit 1 (VKORC1), a Key Protein in the Vitamin K Cycle
|
|---|---|
| Published in |
Molecular Medicine, November 2012
|
| DOI | 10.2119/molmed.2012.00062 |
| Pubmed ID | |
| Authors |
Virginia Pérez-Andreu, Raúl Teruel, Javier Corral, Vanessa Roldán, Nuria García-Barberá, Salam Salloum-Asfar, María José Gómez-Lechón, Stephane Bourgeois, Panos Deloukas, Mia Wadelius, Vicente Vicente, Rocío González-Conejero, Constantino Martínez |
| Abstract |
Regulation of key proteins by microRNAs (miRNAs) is an emergent field in biomedicine. Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) is a relevant molecule for cardiovascular diseases, since it is the target of oral anticoagulant drugs and plays a role in soft tissue calcification. The objective of this study was to determine the influence of miRNAs on the expression of VKORC1. Potential miRNAs targeting VKORC1 mRNA were searched by using online algorithms. Validation studies were carried out in HepG2 cells by using miRNA precursors; direct miRNA interaction was investigated with reporter assays. In silico studies identified two putative conserved binding sites for miR-133a and miR-137 on VKORC1 mRNA. Ex vivo studies showed that only miR-133a was expressed in liver; transfection of miRNA precursors of miR-133a in HepG2 cells reduced VKORC1 mRNA expression in a dose-dependent manner, as assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) as well as protein expression. Reporter assays in HEK293T cells showed that miR-133a interacts with the 3'UTR of VKORC1. Additionally, miR-133a levels correlated inversely with VKORC1 mRNA levels in 23 liver samples from healthy subjects. In conclusion, miR-133a appears to have a direct regulatory effect on expression of VKORC1 in humans; this regulation may have potential importance for anticoagulant therapy or aortic calcification. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 36 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 22% |
| Student > Master | 7 | 19% |
| Student > Bachelor | 4 | 11% |
| Professor > Associate Professor | 3 | 8% |
| Student > Ph. D. Student | 3 | 8% |
| Other | 7 | 19% |
| Unknown | 4 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 13 | 36% |
| Biochemistry, Genetics and Molecular Biology | 6 | 17% |
| Agricultural and Biological Sciences | 5 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Nursing and Health Professions | 2 | 6% |
| Other | 4 | 11% |
| Unknown | 4 | 11% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 November 2012.
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#18,320,524
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Outputs from Molecular Medicine
#903
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Outputs of similar age from Molecular Medicine
#8
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