MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1

Abstract

The microRNAs 19a and 19b, hereafter collectively referred to as miR-19a/b, were recognised to be the most important miRNAs in the oncomiRs-miR-17-92 cluster. However, the exact roles of miR-19a/b in cancers have not been elucidated. In the present study, miR-19a/b was found to be over-expressed in gastric cancer tissues and significantly associated with the patients' metastasis of gastric cancer. Using gain or loss-of-function in in vitro and in vivo experiments, a pro-metastatic function of miR- 19a/b was observed in gastric cancer. Furthermore, reporter gene assay and western blot showed that MXD1 is a direct target of miR-19a/b. Functional assays showed that not only MXD1 had an opposite effect to miR-19a/b in the regulation of gastric cancer cells, but also overexpression of MXD1 reduced both miR-19a/b and c-Myc levels, indicating a potential positive feedback loop among miR-19a/b, MXD1 and c-Myc. In conclusion, miR-17-92 cluster members miR-19a/b facilitated gastric cancer cell migration, invasion and metastasis through targeting the antagonist of c-Myc - MXD1, implicating a novel mechanism for the malignant phenotypes of gastric cancer. © 2014 Macmillan Publishers Limited All rights reserved.