Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.
Analysis of microRNA (miRNA) expression signatures in prostate cancer (PCa) and castration-resistant PCa has revealed that miRNA-223 is significantly downregulated in cancer tissues, suggesting that miR-223 acts as a tumor-suppressive miRNA by targeting oncogenes. The aim of this study was to investigate the functional roles of miR-223 and identify downstream oncogenic targets regulated by miR-223 in PCa cells. Functional studies of miR-223 were carried out to investigate cell proliferation, migration, and invasion using PC3 and PC3M PCa cell lines. Restoration of miR-223 significantly inhibited cancer cell migration and invasion in PCa cells. In silico database and genome-wide gene expression analyses revealed that ITGA3 and ITGB1 were direct targets of miR-223 regulation. Knockdown of ITGA3 and ITGB1 significantly inhibited cancer cell migration and invasion in PCa cells by regulating downstream signaling. Moreover, overexpression of ITGA3 and ITGB1 was observed in PCa clinical specimens. Thus, our data indicated that downregulation of miR-223 enhanced ITGA3/ITGB1 signaling and contributed to cancer cell migration and invasion in PCa cells. Elucidation of the molecular pathways modulated by tumor-suppressive miRNAs provides insights into the mechanisms of PCa progression and metastasis.
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Akira
A
Kurozumi
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Yusuke
Y
Goto
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Ryosuke
R
Matsushita
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Ichiro
I
Fukumoto
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Mayuko
M
Kato
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Rika
R
Nishikawa
Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Shinichi
S
Sakamoto
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Hideki
H
Enokida
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Masayuki
M
Nakagawa
Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Tomohiko
T
Ichikawa
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Naohiko
N
Seki
D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D039422:Integrin alpha3 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
D039422:Integrin alpha3; D019012:Integrin beta1; D035683:MicroRNAs; C000599264:ITGA3 protein, human; C525067:MIR223, human
ITGA3; ITGB1; miR-223; microRNA; prostate cancer