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PLoS One. 2017 Jan 18;12(1):e0170298. doi: 10.1371/journal.pone.0170298. eCollection 2017.

miR 1296-5p Inhibits the Migration and Invasion of Gastric Cancer Cells by Repressing ERBB2 Expression.

Author information

1
Department of Respiration, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, PR China.
2
Department of Thoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
3
Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, PR China.
4
Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing, PR China.
5
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
6
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
7
Department of Physiology, Nanjing Medical University, Nanjing, PR China.
8
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, PR China.
9
Department of Radiation Oncology, Jiangsu Cancer Hospital, Nanjing, PR China.

Abstract

The metastasis of gastric cancer, one of the most common tumors, has a molecular mechanism that is still largely unclear. Here we investigated the role of possible tumor-suppressor miR-1296-5p in the cell migration and invasion of ERBB2-positive gastric cancer. It found that miR-1296-5p was significantly down-regulated in gastric cancer tissues. Moreover, it was down-regulated in lymph node metastatic gastric cancer tissues compared with non-metastatic gastric cancer tissues. The luciferase activity of ERBB2 3'-untranslated region-based reporters constructed in SNU-216 and NUGC-4 gastric cancer cells suggested that ERBB2 was the target gene of miR-1296-5p. Overexpressed miR-1296-5p reduced its target protein level and Rac1 activation, and inhibited the migration and invasion of SNU-216 and NUGC-4 gastric cancer cells. MiR-1296-5p was down-regulated in ERBB2-positive gastric cancer tissues compared with ERBB2-negative gastric cancer tissues. In ERBB2-positive gastric cancers, the miR-1296-5p expression was suppressed in a majority of metastatic lymph node tissues compared to non-metastatic gastric cancer samples. The migration and invasion of gastric cancer cells was inhibited by miR-1296-5p overexpression or herceptin treatment, and rescued by the overexpression of constitutively active Rac1-Q61L or ERBB2. Taken together, our findings first suggest that miR-1296-5p might be involved in the regulation on the migration and invasion of human gastric cancer cells at least in part via targeting ERBB2/Rac1 signaling pathway.

PMID:
28099468
PMCID:
PMC5242522
DOI:
10.1371/journal.pone.0170298
[Indexed for MEDLINE]
Free PMC Article

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