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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

MiR-204 down regulates SIRT1 and reverts SIRT1-induced epithelial-mesenchymal transition, anoikis resistance and invasion in gastric cancer cells

Authors: Lihua Zhang, Xueqing Wang, Pingsheng Chen

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Our previous studies showed that SIRT1 was over-expressed in gastric cancer specimens and related with lymph node metastasis. However, the mechanism of SIRT1 up-regulation and its association with metastasis in gastric cancer remain unclear. The present study was undertaken to understand the role of microRNA in regulation of SIRT1 in the progression of gastric cancer.

Methods

Expression of miR-204 and SIRT1 was assessed in two gastric cancer cell lines and 24 matched cancer specimens. Luciferase reporter assay was carried to verify that miR-204 targeting SIRT1. Cell invasion ability of AGS and BGC was detected by transwell invasion assay. Annexin V/PI assay was used to investigate the cell sensitivity of anoikis. Western blot analysis to assess SIRT1, Vimentin, E-Cadherin, LKB1, and β-actin expression was performed in gastic cancer cell lines.

Results

SIRT1 was defined as the target gene and elucidated the biological functions of miR-204 with a luciferase reporter assay and Western blot analysis. We verified that miR-204 levels were down-regulated and significantly associated with the up-regulation of SIRT1 mRNA levels in gastric cancer specimens. Over-expression of miR-204 reduced cell invasion and anoikis resistance in gastric cancer cells. Up-regulation of miR-204 influenced the levels of the epithelial mesenchymal transition (EMT)-associated genes, increasing E-cadherin levels and decreasing Vimentin levels. We demonstrated that the regulation of EMT by miR-204 involves cooperation with LKB1. Furthermore, silencing of SIRT1 phenocopied the effects of miR-204 in gastric cancer cells. These data demonstrate that miR-204 plays an important role in regulating metastasis of gastric cancer, which is involved in post-transcriptional repression of SIRT1.

Conclusion

Our results suggest that down-regulation of miR-204 promotes gastric cancer cell invasion by activating the SIRT1-LKB1 pathway. These data demonstrate that miR-204 plays an important role in regulating metastasis of gastric cancer, which is involved in post-transcriptional repression of SIRT1.
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Metadata
Title
MiR-204 down regulates SIRT1 and reverts SIRT1-induced epithelial-mesenchymal transition, anoikis resistance and invasion in gastric cancer cells
Authors
Lihua Zhang
Xueqing Wang
Pingsheng Chen
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-290

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