Down‐regulated miR‐625 suppresses invasion and metastasis of gastric cancer by targeting ILK

Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Here, we report that expression of miR‐625 is significantly down‐regulated and negatively correlated with lymph node metastasis in gastric cancer. miR‐625 significantly inhibits invasion and metastasis of gastric cancer cells both in vitro and in vivo. Moreover, we identify that ILK is a direct target gene for miR‐625 and knockdown of ILK has a phenocopy of overexpression of miR‐625. Taken together, our findings suggest that miR‐625 plays an important role in the mechanism of tumor metastasis.

[1]  M. Seto,et al.  MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta. , 2010, Cancer research.

[2]  Min Yan,et al.  microRNA-155 is downregulated in gastric cancer cells and involved in cell metastasis. , 2012, Oncology reports.

[3]  Jianjun Chen,et al.  miR-21 plays a pivotal role in gastric cancer pathogenesis and progression , 2008, Laboratory Investigation.

[4]  Min Liu,et al.  Regulation of the transcription factor NF-κB1 by microRNA-9 in human gastric adenocarcinoma , 2010, Molecular Cancer.

[5]  A. Jemal,et al.  Global Cancer Statistics , 2011 .

[6]  Jung Weon Lee,et al.  Epigenetic regulation of integrin-linked kinase expression depending on adhesion of gastric carcinoma cells. , 2007, American journal of physiology. Cell physiology.

[7]  Y. Yuasa.  Control of gut differentiation and intestinal-type gastric carcinogenesis , 2003, Nature Reviews Cancer.

[8]  J. Massagué,et al.  Cancer Metastasis: Building a Framework , 2006, Cell.

[9]  G. Xiao,et al.  Integrin-linked kinase in gastric cancer cell attachment, invasion and tumor growth. , 2011, World journal of gastroenterology.

[10]  C. Klein,et al.  The Metastasis Cascade , 2008, Science.

[11]  Jianfang Li,et al.  miR-126 functions as a tumour suppressor in human gastric cancer. , 2010, Cancer letters.

[12]  I. Fidler,et al.  Cancer metastasis. , 1991, British medical bulletin.

[13]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[14]  D. Fan,et al.  MiR-218 Inhibits Invasion and Metastasis of Gastric Cancer by Targeting the Robo1 Receptor , 2010, PLoS genetics.

[15]  Kazuhiro Yoshida,et al.  Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma , 2003, Virchows Archiv.

[16]  J. Ju,et al.  MicroRNA-409-3p regulates cell proliferation and apoptosis by targeting PHF10 in gastric cancer. , 2012, Cancer letters.

[17]  Min Liu,et al.  MicroRNA‐23a promotes the growth of gastric adenocarcinoma cell line MGC803 and downregulates interleukin‐6 receptor , 2010, The FEBS journal.

[18]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[19]  R. Sreekumar,et al.  MicroRNA Control of Invasion and Metastasis Pathways , 2011, Front. Gene..

[20]  Hiroki Kuniyasu,et al.  Genes Involved in Invasion and Metastasis of Gastric Cancer Identified by Array-Based Hybridization and Serial Analysis of Gene Expression , 2005, Oncology.

[21]  Chuanyue Wu.  The PINCH-ILK-parvin complexes: assembly, functions and regulation. , 2004, Biochimica et biophysica acta.

[22]  Hui Li,et al.  The molecular mechanism of microRNA-145 to suppress invasion–metastasis cascade in gastric cancer , 2013, Oncogene.

[23]  Y. Zhuang,et al.  Increased miR‐222 in H. pylori‐associated gastric cancer correlated with tumor progression by promoting cancer cell proliferation and targeting RECK , 2012, FEBS letters.

[24]  P. Steeg.  Tumor metastasis: mechanistic insights and clinical challenges , 2006, Nature Medicine.

[25]  K. Legate,et al.  ILK, PINCH and parvin: the tIPP of integrin signalling , 2006, Nature Reviews Molecular Cell Biology.