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The regulatory mechanism of CCR7 gene expression and its involvement in the metastasis and progression of gastric cancer

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Tumor Biology

Abstract

Gastric cancer is the second leading cause of cancer mortality, but the molecular mechanisms underlying its progression and metastasis remain unclear. CCR7 and Dicer 1 protein expression in 80 gastric adenocarcinomas and 40 peritumoral tissues were measured by immunohistochemical staining. The expression of let-7a miRNA in serum, tumor tissues, and peritumoral tissues was measured by real-time PCR. The role of let-7a in CCR7 protein expression, migration, and invasion of gastric cancer cells was tested in vitro. Dicer 1 protein expression was found to be significantly reduced, whereas CCR7 protein expression was significantly increased in gastric adenocarcinomas compared to peritumoral tissues. The let-7a miRNA levels in the serum and tumor tissues of gastric adenocarcinoma patients were significantly lower than in the serum of healthy controls and peritumoral tissues, respectively. Dicer 1 protein positively correlated with let-7a miRNA level, but negatively correlated with CCR7 protein level in gastric adenocarcinoma. Negative Dicer 1 protein and let-7a miRNA expression and positive CCR7 protein expression significantly correlated with lymph node metastasis, depth of invasion, high clinical TNM stage, and larger tumor size. Let-7a transfection significantly inhibited CCR7 protein expression, migration, and invasion of MNK-45 cells in vitro. High expression of CCR7 protein and low expression of Dicer 1 protein and let-7a miRNA are significantly associated with the metastasis and progression of gastric cancer. High CCR7 protein expression may be caused by the loss of Dicer 1 protein expression and reduced let-7a miRNA level in gastric cancer. The serum let-7a level might be a marker for the diagnosis of gastric cancer.

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Acknowledgments

We acknowledge the financial support of the National Hi-tech Program (863 Project) of China (no. 2007AA021804, 2007AA021809).

Conflict of interest

All authors declared no conflict of interest.

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Authors and Affiliations

  1. Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, 410008, China

    Wei-ning Wang, Yuxiang Chen, Yang-de Zhang & Tie-hui Hu

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  1. Wei-ning Wang
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  2. Yuxiang Chen
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  3. Yang-de Zhang
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Correspondence to Tie-hui Hu.

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Wang, Wn., Chen, Y., Zhang, Yd. et al. The regulatory mechanism of CCR7 gene expression and its involvement in the metastasis and progression of gastric cancer. Tumor Biol. 34, 1865–1871 (2013). https://doi.org/10.1007/s13277-013-0728-9

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  • DOI: https://doi.org/10.1007/s13277-013-0728-9

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