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Published in: Annals of Surgical Oncology 3/2012

01-07-2012 | Translational Research and Biomarkers

MicroRNA-200b Regulates Cell Proliferation, Invasion, and Migration by Directly Targeting ZEB2 in Gastric Carcinoma

Authors: Junji Kurashige, MD, Hidenobu Kamohara, MD, PhD, Masayuki Watanabe, MD, PhD, Yukiharu Hiyoshi, MD, PhD, Masaaki Iwatsuki, MD, PhD, Youhei Tanaka, MD, Koichi Kinoshita, MD, Seiya Saito, MD, Yoshifumi Baba, MD, Hideo Baba, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Special Issue 3/2012

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Abstract

Background

The microRNA-200 (miR-200) family has been reported to induce epithelial differentiation and suppress epithelial–mesenchymal transition (EMT) by inhibiting translation of zinc finger E-box-binding homeobox (ZEB) 1 and 2 mRNAs in several types of cancers. This study aimed to clarify the role of miR-200b in regulating EMT and promoting cellular proliferation, invasion, and migration in gastric cancer.

Methods

The relationships among the expression levels of miR-200b, ZEB1 and ZEB2, and E-cadherin mRNAs were analyzed by quantitative real-time reverse transcription–polymerase chain reaction in frozen tissue samples from 40 gastric cancer patients who underwent gastrectomy from 2008 to 2010. The effects of miR-200b on EMT in gastric cancer cells in vitro were also analyzed.

Results

Diffuse histologic type, depth of tumor, tumor size, lymph node metastasis, and lymphatic invasion were significantly higher in the low-miR-200b expression group compared with the high expression group. There was a strong correlation between the levels of miR-200b, and ZEB2 and E-cadherin mRNAs in gastric cancer patients. Upregulation of miR-200b in gastric cancer cells changed the cell morphology from fibroblast- to epithelial-like, associated with localization of E-cadherin to the plasma membrane. ZEB2 mRNA levels fell, while E-cadherin expression levels increased in gastric cells overexpressing miR-200b, associated with significantly reduced cellular proliferation, and inhibition of cellular migration and invasion.

Conclusions

miR-200b regulates ZEB2 expression and thus controls metastasis in gastric cancer.
Appendix
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Metadata
Title
MicroRNA-200b Regulates Cell Proliferation, Invasion, and Migration by Directly Targeting ZEB2 in Gastric Carcinoma
Authors
Junji Kurashige, MD
Hidenobu Kamohara, MD, PhD
Masayuki Watanabe, MD, PhD
Yukiharu Hiyoshi, MD, PhD
Masaaki Iwatsuki, MD, PhD
Youhei Tanaka, MD
Koichi Kinoshita, MD
Seiya Saito, MD
Yoshifumi Baba, MD
Hideo Baba, MD, PhD, FACS
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2217-6

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