miR-133a regulates vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1), a key protein in the vitamin K cycle.

作者: Virginia Pérez-Andreu , Raúl Teruel , Javier Corral , Vanessa Roldán , Nuria García-Barberá

DOI: 10.2119/MOLMED.2012.00062

关键词: Vitamin K epoxide reductaseRegulation of gene expressionTransfectionmicroRNABiologyThree prime untranslated regionVKORC1ReductaseProtein subunitMolecular biology

摘要: Regulation of key proteins by microRNAs (miRNAs) is an emergent field in biomedicine. Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) a relevant molecule for cardiovascular diseases, since it the target oral anticoagulant drugs and plays role soft tissue calcification. The objective this study was to determine influence miRNAs on expression VKORC1. Potential targeting VKORC1 mRNA were searched using online algorithms. Validation studies carried out HepG2 cells miRNA precursors; direct interaction investigated with reporter assays. In silicostudies identified two putative conserved binding sites miR-133a miR-137 mRNA. Ex vivo showed that only expressed liver; transfection precursors reduced dose-dependent manner, as assessed quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) well protein expression. Reporter assays HEK293T interacts 3′UTR Additionally, levels correlated inversely 23 liver samples from healthy subjects. conclusion, appears have regulatory effect humans; regulation may potential importance therapy or aortic

参考文章(24)
TE Klein, RB Altman, Niclas Eriksson, BF Gage, SE Kimmel, MT Lee, NA Limdi, D Page, DM Roden, MJ Wagner, MD Caldwell, JA Johnson, YT Chen, MS Wen, Y Caraco, I Achache, S Blotnick, M Muszkat, JG Shin, HS Kim, G Suarez-Kurtz, JA Perini, E Silva-Assuncao, JL Anderson, BD Horne, JF Carlquist, RL Berg, JK Burmester, BC Goh, SC Lee, F Kamali, E Sconce, AK Daly, AH Wu, TY Langaee, H Feng, L Cavallari, K Momary, M Pirmohamed, A Jorgensen, CH Toh, P Williamson, H McLeod, JP Evans, KE Weck, C Brensinger, Y Nakamura, T Mushiroda, D Veenstra, L Meckley, MJ Rieder, AE Rettie, M Wadelius, H Melhus, CM Stein, U Schwartz, D Kurnik, E Deych, P Lenzini, C Eby, LY Chen, P Deloukas, A Motsinger-Reif, H Sagreiya, BS Srinivasan, E Lantz, T Chang, M Ritchie, LS Lu, Estimation of the warfarin dose with clinical and pharmacogenetic data The New England Journal of Medicine. ,vol. 360, pp. 753- 764 ,(2009) , 10.1056/NEJMOA0809329
Johannes Oldenburg, Milka Marinova, Clemens Müller‐Reible, Matthias Watzka, The vitamin K cycle. Vitamins and Hormones Series. ,vol. 78, pp. 35- 62 ,(2008) , 10.1016/S0083-6729(07)00003-9
R. TERUEL, C. PÉREZ-SÁNCHEZ, J. CORRAL, M. T. HERRANZ, V. PÉREZ-ANDREU, E. SAIZ, N. GARCÍA-BARBERÁ, I. MARTÍNEZ-MARTÍNEZ, V. ROLDÁN, V. VICENTE, C. LÓPEZ-PEDRERA, C. MARTÍNEZ, Identification of miRNAs as potential modulators of tissue factor expression in patients with systemic lupus erythematosus and antiphospholipid syndrome Journal of Thrombosis and Haemostasis. ,vol. 9, pp. 1985- 1992 ,(2011) , 10.1111/J.1538-7836.2011.04451.X
Eric M. Small, Eric N. Olson, Pervasive roles of microRNAs in cardiovascular biology Nature. ,vol. 469, pp. 336- 342 ,(2011) , 10.1038/NATURE09783
Deeb N. Salem, Patrick T. O'Gara, Christopher Madias, Stephen G. Pauker, Valvular and Structural Heart Disease Chest. ,vol. 133, pp. 593S- 629S ,(2008) , 10.1378/CHEST.08-0724
WH Davin Townley-Tilson, Thomas E Callis, DaZhi Wang, None, MicroRNAs 1, 133, and 206: Critical factors of skeletal and cardiac muscle development, function, and disease The International Journal of Biochemistry & Cell Biology. ,vol. 42, pp. 1252- 1255 ,(2010) , 10.1016/J.BIOCEL.2009.03.002
Bríd M. Ryan, Ana I. Robles, Curtis C. Harris, Genetic variation in microRNA networks: the implications for cancer research Nature Reviews Cancer. ,vol. 10, pp. 389- 402 ,(2010) , 10.1038/NRC2867
Karen Meir, Elina Khvalevsky, Yael Spector, Nathan Rojansky, Zvi Bentwich, Benjamin E. Reubinoff, Eithan Galun, Comprehensive Gene and microRNA Expression Profiling Reveals a Role for microRNAs in Human Liver Development PLoS ONE. ,vol. 4, pp. e7511- ,(2009) , 10.1371/JOURNAL.PONE.0007511
P. J. Mishra, R. Humeniuk, P. J. Mishra, G. S. A. Longo-Sorbello, D. Banerjee, J. R. Bertino, A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 104, pp. 13513- 13518 ,(2007) , 10.1073/PNAS.0706217104
Peter Brodersen, Olivier Voinnet, Revisiting the principles of microRNA target recognition and mode of action Nature Reviews Molecular Cell Biology. ,vol. 10, pp. 141- 148 ,(2009) , 10.1038/NRM2619