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

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.

• Authors: Wei-ning Wang, Yuxiang Chen, Yang-de Zhang, Tie-hui Hu
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 34 Issue 3 Pg. 1865-71 (Jun 2013) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 23519840 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCR7 protein, human
• MicroRNAs
• RNA, Messenger
• Receptors, CCR7
• mirnlet7 microRNA, human
• DICER1 protein, human
• Ribonuclease III
• DEAD-box RNA Helicases

Topics

• Adenocarcinoma (genetics, metabolism, pathology)
• Adult
• Aged
• Blotting, Western
• Cell Differentiation
• Cell Movement
• Cell Proliferation
• DEAD-box RNA Helicases (genetics, metabolism)
• Female
• Humans
• Immunoenzyme Techniques
• Lymphatic Metastasis
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Staging
• Prognosis
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Receptors, CCR7 (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Ribonuclease III (genetics, metabolism)
• Stomach Neoplasms (genetics, metabolism, pathology)