MicroRNA MiR-17 retards tissue growth and represses fibronectin expression.
MicroRNAs (miRNAs) are single-stranded regulatory RNAs, frequently expressed as clusters. Previous studies have demonstrated that the six-miRNA cluster miR-17~92 has important roles in tissue development and cancers. However, the precise role of each miRNA in the cluster is unknown. Here we show that overexpression of miR-17 results in decreased cell adhesion, migration and proliferation. Transgenic mice overexpressing miR-17 showed overall growth retardation, smaller organs and greatly reduced haematopoietic cell lineages. We found that fibronectin and the fibronectin type-III domain containing 3A (FNDC3A) are two targets that have their expression repressed by miR-17, both in vitro and in transgenic mice. Several lines of evidence support the notion that miR-17 causes cellular defects through its repression of fibronectin expression. Our single miRNA expression assay may be evolved to allow the manipulation of individual miRNA functions in vitro and in vivo. We anticipate that this could serve as a model for studying gene regulation by miRNAs in the development of gene therapy.
Shan
Sze Wan
SW
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada.
Lee
Daniel Y
DY
Deng
Zhaoqun
Z
Shatseva
Tatiana
T
Jeyapalan
Zina
Z
Du
William W
WW
Zhang
Yaou
Y
Xuan
Jim W
JW
Yee
Siu-Pok
SP
Siragam
Vinayakumar
V
Yang
Burton B
BB
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005353:Fibronectins / Q000235:genetics*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014162:Transfection
D005353:Fibronectins; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse