Tumor‐suppressive microRNA‐223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer

• Published in: Cancer science Vol. 107; no. 1; pp. 84 - 94
• Main Authors: Kurozumi, Akira, Goto, Yusuke, Matsushita, Ryosuke, Fukumoto, Ichiro, Kato, Mayuko, Nishikawa, Rika, Sakamoto, Shinichi, Enokida, Hideki, Nakagawa, Masayuki, Ichikawa, Tomohiko, Seki, Naohiko
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.01.2016
• Subjects: Aged; Aged, 80 and over; Blotting, Western; Cell Line, Tumor; Cell Movement; Gene Expression Regulation, Neoplastic - genetics; Gene Knockdown Techniques; Humans; Immunohistochemistry; Integrin alpha3 - metabolism; Integrin beta1 - metabolism; ITGA3; ITGB1; Male; microRNA; MicroRNAs - genetics; Middle Aged; miR‐223; Neoplasm Invasiveness - genetics; Original; prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Real-Time Polymerase Chain Reaction; Signal Transduction - genetics; Transfection; ITGB1; miR-223; microRNA; prostate cancer; ITGA3
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12842

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. 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.