Open AccessTumor‐suppressive micro RNA ‐223 inhibits cancer cell migration and invasion by targeting ITGA 3/ ITGB 1 signaling in prostate cancer
Author(s) -
Kurozumi Akira,
Goto Yusuke,
Matsushita Ryosuke,
Fukumoto Ichiro,
Kato Mayuko,
Nishikawa Rika,
Sakamoto Shinichi,
Enokida Hideki,
Nakagawa Masayuki,
Ichikawa Tomohiko,
Seki Naohiko
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12842
Subject(s) - cancer research , gene knockdown , prostate cancer , downregulation and upregulation , cancer , cell migration , microrna , metastasis , biology , cancer cell , cell growth , cell , rna , cell culture , gene , biochemistry , genetics
Analysis of micro RNA (mi RNA ) expression signatures in prostate cancer ( PC a) and castration‐resistant PC a has revealed that mi RNA ‐223 is significantly downregulated in cancer tissues, suggesting that miR‐223 acts as a tumor‐suppressive mi RNA 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 PC a cells. Functional studies of miR‐223 were carried out to investigate cell proliferation, migration, and invasion using PC 3 and PC 3M PC a cell lines. Restoration of miR‐223 significantly inhibited cancer cell migration and invasion in PC a cells. In silico database and genome‐wide gene expression analyses revealed that ITGA 3 and ITGB 1 were direct targets of miR‐223 regulation. Knockdown of ITGA 3 and ITGB 1 significantly inhibited cancer cell migration and invasion in PC a cells by regulating downstream signaling. Moreover, overexpression of ITGA 3 and ITGB 1 was observed in PC a clinical specimens. Thus, our data indicated that downregulation of miR‐223 enhanced ITGA 3/ ITGB 1 signaling and contributed to cancer cell migration and invasion in PC a cells. Elucidation of the molecular pathways modulated by tumor‐suppressive mi RNA s provides insights into the mechanisms of PC a progression and metastasis.