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Gastric Cancer
Published in: Gastric Cancer 4/2011

01-10-2011 | Original article

A small interfering RNA targeting the KLF6 splice variant, KLF6-SV1, as gene therapy for gastric cancer

Authors: Hui Chen, Lili Chen, Lingyu Sun, Hongqun Zhen, Xiaomei Li, Qifan Zhang

Published in: Gastric Cancer | Issue 4/2011

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Abstract

Background

Accumulating evidence suggests that the tumor suppressor gene Kruppel-like factor 6 (KLF6) and its dominant-negative splice form KLF6-SV1 play important roles in both the development and progression of cancer. However, the role of KLF6-SV1 in gastric cancer remains largely unknown.

Methods

KLF6-SV1 expression was detected in various human gastric cancer cell lines and gastric cancer patient samples by reverse transcriptase polymerase chain reaction (RT–PCR) and Western blotting. Small interfering RNA (siRNA) was used to inhibit KLF6-SV1 expression in BGC-823 and SGC-7901 cell lines. The effects of downregulation of KLF6-SV1 by siRNA on cell proliferation, migration, invasion, and tumor growth were examined in vitro and in vivo.

Results

Overexpression of KLF6-SV1 was detected in tumor samples from gastric cancer patients, and in various differentiated gastric cancer cell lines. In vitro downregulation of KLF6-SV1 by siRNA inhibited BGC-823 and SGC-7901 cell proliferation, anchorage-independent growth, migration, and invasion through the altered expression of Ki-67, vascular endothelial growth factor (VEGF), E-cadherin, and matrix metalloproteinase (MMP)-9. Also, KLF6-SV1 silencing promoted caspase-dependent apoptosis of BGC-823 and SGC-7901 cells via the regulation of phosphatidylinositol 3-OH kinase (PI3K)/Akt activity and Bcl-2-related protein expression. In vivo animal studies showed that KLF6-SV1 siRNA significantly inhibited the tumorigenicity of BGC-823 and SGC-7901 cells. Gene therapy with polyethylenimine/si-SV1 intratumoral injection also resulted in the suppression of tumor growth and prolonged animal survival in an established xenograft tumor model.

Conclusion

These data demonstrate that KLF6-SV1 is an important regulator of the growth, migration, invasion, and survival of gastric cancer cells, and downregulation of KLF6-SV1 by siRNA may offer a new potential gene therapy approach for gastric cancer.
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Metadata
Title
A small interfering RNA targeting the KLF6 splice variant, KLF6-SV1, as gene therapy for gastric cancer
Authors
Hui Chen
Lili Chen
Lingyu Sun
Hongqun Zhen
Xiaomei Li
Qifan Zhang
Publication date
01-10-2011
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 4/2011
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-011-0049-x

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