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.
Highlights
Gastric cancer, regarded as the culprit for cancer-caused deaths, is rampant across Asia [1]
MiR-1296-5p is down-regulated in metastatic gastric cancer tissues
We found that miR-1296-5p expression was significantly down-regulated in gastric cancer tissues compared with the non-tumor adjacent normal tissues (Fig 1A)
Summary
Gastric cancer, regarded as the culprit for cancer-caused deaths, is rampant across Asia [1]. In triple negative breast cancer (TNBC) cell lines and tissues samples, miR-1296 expression was significantly suppressed and increased the sensitiveness of TNBC cells to cisplatin treatment [5]. In the apoptosis triggered by PI (a novel synthesized small-molecule compound) in the condition of cervical cancer, miR1296 could make changes in the PIM1-STAT3 pathway [7]. In spite of these findings, more efforts should be done to reveal how specific miRNAs alter the migration of gastric cancer cells
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