miR-183 inhibits invasion of gastric cancer by targeting Ezrin.

miR-183, a member of an evolutionarily conserved miRNA cluster (miR-96, miR-182, and miR-183), has been demonstrated to act as both a tumor suppressor and oncogene in various type of human cancer. However, the biological role of miR-183 in gastric cancer (GC) still remains unclear. In the present study, miR-183 expression was significantly decreased in gastric cancer tissues compared with its' adjacent normal tissues, and down-regulation of miR-183 was significantly associated with lymph node metastasis and pathological TNM stage. Furthermore, Erzin, which was reported to be up-regulated in gastric cancer, was identified as an efficient target of miR-183. Overexpression of miR-183 markedly suppressed cells invasion by downregulation of Ezrin expression. However, miR-183 expression didn't affect cells proliferation and cell cycle distribution of GC. In conclusion, our study demonstrated that miR-183 acts as a tumor suppressor in GC, partially at least via regulation of Ezrin. Therefore, miR-183 may be a potential target for the treatment of gastric cancer.

[1]  Y. Teng,et al.  MicroRNA‐183 suppresses retinoblastoma cell growth, invasion and migration by targeting LRP6 , 2014, The FEBS journal.

[2]  P. Sethupathy,et al.  Abstract 24: MicroRNA-27b Is a Regulatory Hub in Lipid Metabolism and Is Altered in Dyslipidemia , 2012, Arteriosclerosis, Thrombosis, and Vascular Biology.

[3]  P. Suh,et al.  Alterations in cell proliferation related gene expressions in gastric cancer. , 2011, Critical Reviews in Eukaryotic Gene Expression.

[4]  W. Ping,et al.  miR-138-5p reverses gefitinib resistance in non-small cell lung cancer cells via negatively regulating G protein-coupled receptor 124. , 2014, Biochemical and biophysical research communications.

[5]  K. Hunter Ezrin, a key component in tumor metastasis. , 2004, Trends in molecular medicine.

[6]  Ling Yang,et al.  Incidence and mortality of gastric cancer in China. , 2006, World journal of gastroenterology.

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

[8]  B. Liu,et al.  MiR-132 Suppresses the Migration and Invasion of Lung Cancer Cells via Targeting the EMT Regulator ZEB2 , 2014, PloS one.

[9]  M. Mochizuki,et al.  Effects of transplantation sites on tumour growth, pulmonary metastasis and ezrin expression of canine osteosarcoma cell lines in nude mice. , 2012, Veterinary and comparative oncology.

[10]  Subbaya Subramanian,et al.  MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. , 2010, Cancer research.

[11]  J. Siewert,et al.  Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. , 1998, Annals of surgery.

[12]  Deng-feng Li,et al.  MiRNA-107 inhibits proliferation and migration by targeting CDK8 in breast cancer. , 2014, International journal of clinical and experimental medicine.

[13]  L. Li,et al.  MicroRNA-145 inhibits tumour growth and metastasis in colorectal cancer by targeting fascin-1 , 2014, British Journal of Cancer.

[14]  O. Volpert,et al.  miR-200b Inhibits Prostate Cancer EMT, Growth and Metastasis , 2013, PloS one.

[15]  Lei Wang,et al.  Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R , 2014, BMC Cancer.

[16]  Hui Gao,et al.  Expression of ezrin correlates with malignant phenotype of lung cancer, and in vitro knockdown of ezrin reverses the aggressive biological behavior of lung cancer cells , 2012, Tumor Biology.

[17]  H. Bonkovsky,et al.  Inhibitory effects of microRNA 19b in hepatic stellate cell‐mediated fibrogenesis , 2012, Hepatology.

[18]  Bin Wang,et al.  MicroRNA-10a Is Down-Regulated by DNA Methylation and Functions as a Tumor Suppressor in Gastric Cancer Cells , 2014, PloS one.

[19]  Sara M. Johnson,et al.  Translational research in gastric malignancy. , 2008, Surgical oncology clinics of North America.

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

[21]  Michael J Kerin,et al.  Dysregulated miR-183 inhibits migration in breast cancer cells , 2010, BMC Cancer.

[22]  Junfeng Zhu,et al.  Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting Ezrin. , 2012, The American journal of pathology.

[23]  Xiaofei Zheng,et al.  miR-183 inhibits TGF-β1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells , 2010, BMC Cancer.

[24]  Feng Xu,et al.  microRNA-200a inhibits cell proliferation by targeting mitochondrial transcription factor A in breast cancer. , 2014, DNA and cell biology.

[25]  H. Aburatani,et al.  Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. , 2001, Cancer research.

[26]  L. Tang,et al.  MiR-99a Antitumor Activity in Human Breast Cancer Cells through Targeting of mTOR Expression , 2014, PloS one.

[27]  C. V. D. Velde,et al.  Gastric cancer , 2009, The Lancet.

[28]  Jian Wang,et al.  MiR‐145, miR‐133a and miR‐133b inhibit proliferation, migration, invasion and cell cycle progression via targeting transcription factor Sp1 in gastric cancer , 2014, FEBS letters.

[29]  Haien Zhao,et al.  miR-183 inhibits the metastasis of osteosarcoma via downregulation of the expression of Ezrin in F5M2 cells , 2012, International journal of molecular medicine.

[30]  Ying Zhu,et al.  MicroRNA-484 is more highly expressed in serum of early breast cancer patients compared to healthy volunteers , 2014, BMC Cancer.

[31]  R. Dahiya,et al.  microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer , 2013, British Journal of Cancer.

[32]  C. Zheng,et al.  Effect of negative lymph node count on survival for gastric cancer after curative distal gastrectomy. , 2011, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[33]  Xuemei Ma,et al.  Differential expression of serum miR-126, miR-141 and miR-21 as novel biomarkers for early detection of liver metastasis in colorectal cancer. , 2014, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[34]  M. Hollingsworth,et al.  High levels of ezrin expressed by human pancreatic adenocarcinoma cell lines with high metastatic potential. , 1999, Biochemical and biophysical research communications.

[35]  Lei Zhang,et al.  MiR-361-5p acts as a tumor suppressor in prostate cancer by targeting signal transducer and activator of transcription-6(STAT6). , 2014, Biochemical and biophysical research communications.

[36]  Y. Zhong,et al.  MicroRNA-31 contributes to colorectal cancer development by targeting factor inhibiting HIF-1α (FIH-1) , 2014, Cancer biology & therapy.

[37]  W. Xia,et al.  Hsa-mir-182 downregulates RASA1 and suppresses lung squamous cell carcinoma cell proliferation. , 2014, Clinical laboratory.

[38]  Juan Xie,et al.  miR-7 inhibits the invasion and metastasis of gastric cancer cells by suppressing epidermal growth factor receptor expression. , 2014, Oncology reports.

[39]  Shu Zheng,et al.  MicroRNA‐183 regulates Ezrin expression in lung cancer cells , 2008, FEBS letters.

[40]  Andreas Günther,et al.  miR-142-3p balances proliferation and differentiation of mesenchymal cells during lung development , 2014, Development.