MiR-137 regulates epithelial-mesenchymal transition in gastrointestinal stromal tumor.

Abstract

Activation of the epithelial-to-mesenchymal transition (EMT) endows extraordinary invasive capability of cancer cells and causes of treatment failure and metastasis in gastrointestinal stromal tumor (GIST); however, the molecular mechanisms governing GIST invasion remain largely unknown. MicroRNAs (miRNAs) have been shown to play critical roles in cell motility and invasion, which promotes us to study the biological functions of miR-137 in the EMT of GIST. We have found that miR-137 was dramatically downregulated in clinical specimen of GIST. Using an in silico analysis approach, Twist1, a key regulator gene of EMT, has been identified as the target of miR-137. Quantitative RT-PCT and western blot were used to confirm that miR-137 directly targeted on Twist1 and repressed Twist1 expression in GIST-H1 human gastrointestinal stromal tumor cell line. Further, miR-137 was found to increase expression of E-cadherin and cytokeratin, but suppress expression of N-cadherin and vimentin. In vitro experiments have shown that miR-137 enhanced the epithelial cell morphology, decreased GIST cell migration, activated G1 cell cycle arrest, and induced cell apoptosis. These results suggest a novel mechanism that miR-137 regulates EMT and inhibits cell migration via Twist1 downregulation. Therefore, miR-137 may function as anti-migration and anti-metastasis in GIST and our study provides a potential approach for developing miR-137-based therapeutic strategy for GIST.