miR-543 inhibits tumor malignant progression by regulating TWIST1 in human gastric cancer

Abstract Background: TWIST1, a highly conserved basic helix-loop-helix (bHLH) transcription factor, is essential to epithelial-mesenchymal transition (EMT) and cancer metastasis in gastric cancer (GC). However, little is known about the post-transcriptional regulation of TWIST1, especially the mechanisms involving microRNAs. Methods: TWIST1 expression were observed on 107 cases of gastric cancer through tissue microarray technology to identify their correlations with clinicopathological parameters and patient survival. The regulation of TWIST1 by miR-543 was confirmed by western blot, dual luciferase activity assays and rescue experiments. Moreover, the functions of miR-543 on cell migration, invasion, tumorigenicity and metastatic potential were evaluated by stably expression strategy in vitro and in vivo. Results: TWIST1 is overexpressed in 74 of 107 GC tumor samples. High TWIST1 expression positively correlated with poor prognosis of GC patients. In addition, TWIST1 was found to be a direct target of miR-543. Expression of miR-543 was obviously decreased in GC cell lines and primary tissues. Overexpression of miR-543 in GC cells inhibited proliferation, colony formation, migration and invasion by suppressing expression of TWIST1. Ectopic expression of miR-543 inhibited tumor growth and prevented liver metastasis of gastric cancer cells in mice. Conclusion: TWIST1 is overexpressed in gastric cancer and regulated by miR-543. Downregulated miR-543 promotes tumor growth and metastasis of GC, indicating the possibility of new strategies for GC therapy.