MicroRNA expression and functional profiles of osteosarcoma.
OBJECTIVE
Osteosarcoma (OS) is the most frequent primary malignant bone tumor in children and young adults. Although the introduction of combined neoadjuvant chemotherapy has significantly prolonged survival, the outcome for OS patients showing a poor response to chemotherapy is still unfavorable. In order to develop new therapeutic approaches, elucidation of the entire molecular pathway regulating OS cell proliferation would be desirable.


METHODS
MicroRNA (miRNA) are highly conserved noncoding RNA that play important roles in the development and progression of various other cancers. Using miRNA microarrays capable of detecting a known number of 933 miRNA, 108 miRNA were found to be commonly expressed in 24 samples of OS tissue and subjected to a cell proliferation assay.


RESULTS
We found that inhibition of 5 let-7 family miRNA (hsa-let-7a, b, f, g and i) significantly suppressed the proliferation of OS cells. Using a quantitative shotgun proteomics approach, we also found that the let-7 family miRNA regulated the expression of vimentin and serpin H1 proteins.


CONCLUSIONS
Our present results indicate the involvement of let-7 family miRNA in regulation of the cell proliferation as well as epithelial-mesenchymal transition of OS. Thus, let-7 family miRNA may potentially provide novel targets for the development of therapeutic strategies against OS.
Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan.
Eisuke
E
Kobayashi
Reiko
R
Satow
Masaya
M
Ono
Mari
M
Masuda
Kazufumi
K
Honda
Tomohiro
T
Sakuma
Akira
A
Kawai
Hideo
H
Morioka
Yoshiaki
Y
Toyama
Tesshi
T
Yamada
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050958:HSP47 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D059467:Transcriptome; D014746:Vimentin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D050958:HSP47 Heat-Shock Proteins; D035683:MicroRNAs; D014746:Vimentin; C487931:mirnlet7 microRNA, human