miR-137 Is Frequently Down-Regulated in Gastric Cancer and Is a Negative Regulator of Cdc42

被引：119

作者：

Chen, Qingjiang ^{[1
]}

Chen, Xiaobing ^{[2
]}

Zhang, Mingzhi ^{[1
]}

Fan, Qingxia ^{[1
]}

Luo, Suxia ^{[2
]}

Cao, Xinguang ^{[2
]}

机构：

[1] Zhengzhou Univ, Dept Med Oncol, Affiliated Hosp 1, Zhengzhou 450000, Peoples R China

[2] Zhengzhou Univ, Dept Internal Med Oncol, Henan Canc Hosp, Affiliated Canc Hosp, Zhengzhou 450000, Peoples R China

来源：

DIGESTIVE DISEASES AND SCIENCES | 2011年 / 56卷 / 07期

关键词：

miR-137; Gastric cancer; Hypermethylation; Cdc42; MICRORNAS; DIFFERENTIATION; PROLIFERATION; GTPASES; DEATH; RAC1;

D O I：

10.1007/s10620-010-1536-3

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

MicroRNAs (miRNAs) are a class of small (19-25 nucleotides) noncoding RNAs that regulate the expressions of a wide variety of genes, including some involved in cancer development. Some recent studies show that DNA methylation contributes to down-regulation of microRNA-137 (miR-137) during tumorigenesis. Whether down-regulation of miR-137 also exists in gastric cancer is unknown. Our aim was to test the hypothesis that down-regulation of miR-137 also exists in gastric cancer. Expression of levels of miR-137 were examined using real-time PCR on paired gastric cancer and adjacent non-cancerous tissues. The methylation status is detected by MSP. Results show that miR-137 is downregulated by hypermethylation of the promoter in gastric cancer tissues. Epigenetic silencing of miR-137 induced an up-regulation of its targets, Cdc42. Restoration of the miR-137 expression in gastric cancer cell lines downregulated the Cdc42 expression. Restoration of the miR-137 and inactivation of Cdc42 induce apoptosis and cell cycle G1 arrest in gastric cancer cells. Furthermore, the miR-137 expression was found to be inversely correlated with CDC42 expression in gastric caner. miR-137 is frequently down-regulated in gastric cancer and is a negative regulator of Cdc42.

引用

页码：2009 / 2016

页数：8

共 17 条

[1] Epigenetic Silencing of miR-137 Is an Early Event in Colorectal Carcinogenesis [J].

Balaguer, Francesc ;

Link, Alexander ;

Lozano, Juan Jose ;

Cuatrecasas, Miriam ;

Nagasaka, Takeshi ;

Boland, C. Richard ;

Goel, Ajay .

CANCER RESEARCH, 2010, 70 (16) :6609-6618

[2] MicroRNA-137 targets microphthalmia-associated transcription factor in melanoma cell lines [J].

Bemis, Lynne T. ;

Chen, Robert ;

Amato, Carol M. ;

Classen, Elizabeth H. ;

Robinson, Steven E. ;

Coffey, David G. ;

Erickson, Paul F. ;

Shellman, Yiqun G. ;

Robinson, William A. .

CANCER RESEARCH, 2008, 68 (05) :1362-1368

[3]

Del Pulgar TG, 2008, INT J ONCOL, V33, P185

[4] Genomic Profiling of MicroRNAs in Bladder Cancer: miR-129 Is Associated with Poor Outcome and Promotes Cell Death In vitro [J].

Dyrskjot, Lars ;

Ostenfeld, Marie S. ;

Bramsen, Jesper B. ;

Silahtaroglu, Asli N. ;

Lamy, Philippe ;

Ramanathan, Ramshanker ;

Fristrup, Niels ;

Jensen, Jens L. ;

Andersen, Claus L. ;

Zieger, Karsten ;

Kauppinen, Sakari ;

Ulhoi, Benedicte P. ;

Kjems, Jorgen ;

Borre, Michael ;

Orntoft, Torben F. .

CANCER RESEARCH, 2009, 69 (11) :4851-4860

[5] The Cdc42-interacting Protein-4 (CIP4) Gene Knock-out Mouse Reveals Delayed and Decreased Endocytosis [J].

Feng, Yanming ;

Hartig, Sean M. ;

Bechill, John E. ;

Blanchard, Elisabeth G. ;

Caudell, Eva ;

Corey, Seth J. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (07) :4348-4354

[6] Epigenetic Repression of microRNA-129-2 Leads to Overexpression of SOX4 Oncogene in Endometrial Cancer [J].

Huang, Yi-Wen ;

Liu, Joseph C. ;

Deatherage, Daniel E. ;

Luo, Jingqin ;

Mutch, David G. ;

Goodfellow, Paul J. ;

Miller, David S. ;

Huang, Tim H-M. .

CANCER RESEARCH, 2009, 69 (23) :9038-9046

[7] Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer [J].

Kamai, T ;

Yamanishi, T ;

Shirataki, H ;

Takagi, K ;

Asami, H ;

Ito, Y ;

Yoshida, KI .

CLINICAL CANCER RESEARCH, 2004, 10 (14) :4799-4805

[8] Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer [J].

Kozaki, Ken-ichi ;

Imoto, Issei ;

Mogi, Seiki ;

Omura, Ken ;

Inazawa, Johji .

CANCER RESEARCH, 2008, 68 (07) :2094-2105

[9] MicroRNA-137 promoter methylation in oral rinses from patients with squamous cell carcinoma of the head and neck is associated with gender and body mass index [J].

Langevin, Scott M. ;

Stone, Roslyn A. ;

Bunker, Clareann H. ;

Grandis, Jennifer R. ;

Sobol, Robert W. ;

Taioli, Emanuela .

CARCINOGENESIS, 2010, 31 (05) :864-870

[10]

LIU M, INT J CANC IN PRESS

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