MicroRNA-1 (miR-1) inhibits chordoma cell migration and invasion by targeting slug.
Recent studies have revealed that expression of miRNA-1 (miR-1) is frequently down-regulated in several cancer types including chordoma. Identifying and validating novel targets of miR-1 is useful for understanding the roles of miR-1 in chordoma. We aimed to further investigate the functions of miR-1 in chordoma. Specifically, we assessed whether restoration of miR-1 affects cell migration and invasion in chordoma, and focused on the miR-1 potential target Slug gene. Migratory and invasive activities were assessed by wound healing and Matrigel invasion assays, respectively. Cell proliferation was determined by MTT assay. Slug expression was evaluated by Western blot, immunofluorescence, and immunohistochemistry. Restoration of miR-1 expression suppressed the migratory and invasive activities of chordoma cells. Transfection of miR-1 inhibited cell proliferation both time- and dose-dependently in chordoma. MiR-1 transfected cells showed inhibited Slug expression. Slug was over-expressed in chordoma cell lines and advanced chordoma tissues. In conclusion, we have shown that miR-1 directly targets the Slug gene in chordoma. Restoration of miR-1 suppressed not only proliferation, but also migratory and invasive activities, and reduced the Slug expression in chordoma cells. These results collectively indicate that miR-1/Slug pathway is a potential therapeutic target because of its crucial roles in chordoma cell growth and migration.
Sarcoma Biology Laboratory, Department of Orthopedic Surgery, Massachusetts General Hospital, 50 Fruit Street, Jackson 1115, Boston, Massachusetts, 02114; Department of Orthopaedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan.
Eiji
E
Osaka
Xiaoqian
X
Yang
Jacson K
JK
Shen
Pei
P
Yang
Yong
Y
Feng
Henry J
HJ
Mankin
Francis J
FJ
Hornicek
Zhenfeng
Z
Duan
D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D002817:Chordoma / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology* / Q000627:therapeutic use; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects*
C544547:MIRN1 microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
chordoma; invasion; miRNA-1 (miR-1); migration; slug