Open AccessTumor‐suppressive micro RNA ‐218 inhibits cancer cell migration and invasion via targeting of LASP 1 in prostate cancer
Author(s) -
Nishikawa Rika,
Goto Yusuke,
Sakamoto Shinichi,
Chiyomaru Takeshi,
Enokida Hideki,
Kojima Satoko,
Kinoshita Takashi,
Yamamoto Noriko,
Nakagawa Masayuki,
Naya Yukio,
Ichikawa Tomohiko,
Seki Naohiko
Publication year - 2014
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.12441
Subject(s) - carcinogenesis , cancer research , metastasis , microrna , biology , prostate cancer , downregulation and upregulation , cancer cell , cancer , cell migration , cell , microbiology and biotechnology , gene , biochemistry , genetics
Our recent studies of the micro RNA (mi RNA ) expression signature in prostate cancer ( PC a) indicated that mi RNA ‐218 ( miR‐218 ) was significantly downregulated in clinical specimens, suggesting that miR‐218 might act as a tumor‐suppressive mi RNA in PC a. The aim of the present study was to investigate the functional significance of miR‐218 in PC a and to identify novel miR‐218 ‐regulated cancer pathways and target genes involved in PC a oncogenesis and metastasis. Restoration of miR‐218 in PC a cell lines ( PC 3 and DU 145) revealed that this mi RNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that LIM and SH 3 protein 1 ( LASP 1) is a potential target of miR‐218 regulation. LASP 1 is a cytoskeletal scaffold protein that plays critical roles in cytoskeletal organization and cell migration. Luciferase reporter assays showed that miR‐218 directly regulated expression of LASP 1 . Moreover, downregulating the LASP 1 gene significantly inhibited cell migration and invasion in cancer cells, and the expression of LASP 1 was upregulated in cancer tissues. We conclude that loss of tumor‐suppressive miR‐218 enhanced cancer cell migration and invasion in PC a through direct regulation of LASP 1 . Our data on pathways regulated by tumor‐suppressive miR‐218 provide new insight into the potential mechanisms of PC a oncogenesis and metastasis.