MicroRNA-31 regulated by the extracellular regulated kinase is involved in vascular smooth muscle cell growth via large tumor suppressor homolog 2.
Aberrant growth of vascular smooth muscle cells (VSMCs) is a major cellular event in the pathogenesis of many proliferative vascular diseases. Recently, microRNA-31 (miR-31) has been found to play a critical role in cancer cell proliferation. However, the biological role of miR-31 in VSMC growth and the mechanisms involved are currently unknown. In the present study, the expression of rat mature miR-31 (rno-miR-31) was determined in cultured VSMCs and in rat carotid arteries. We identified that rno-miR-31 is an abundant miRNA in VSMCs, and its expression was significantly increased in proliferative VSMCs and in vascular walls with neointimal growth. The up-regulation of rno-miR-31 in proliferative VSMCs was inhibited by the inhibitor of mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK). By both gain-of-function and loss-of-function approaches, we demonstrated that rno-miR-31 had a proproliferative effect on VSMCs. We further identified that LATS2 (large tumor suppressor homolog 2) is a downstream target gene product of rno-miR-31 that is involved in rno-miR-31-mediated effect on VSMC proliferation. The LATS2 as a target gene protein of rno-miR-31 is verified in vivo in balloon-injured rat carotid arteries. The results suggest that MAPK/ERK/miR-31/LATS2 may represent a novel signaling pathway in VSMC growth. miR-31 is able to enhance VSMC proliferation via its downstream target gene product, LATS2.
RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101.
Xiaojun
X
Liu
RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101.
Yunhui
Y
Cheng
RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101.
Xiuwei
X
Chen
RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101.
Jian
J
Yang
RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101.
Ling
L
Xu
RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101. Electronic address: zhangc3@umdnj.edu.
Chunxiang
C
Zhang
D000818:Animals; D002339:Carotid Arteries / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C534612:MIRN31 microRNA, human; C570112:MIRN31 microRNA, rat; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases