MicroRNA-141 inhibits tumor growth and metastasis in gastric cancer by directly targeting transcriptional co-activator with PDZ-binding motif, TAZ

摘要

Gastric cancer (GC) is a biologically heterogeneous disease accompanying various genetic and epigenetic alterations, and the molecular mechanisms underlying this disease are complex and not completely understood. Increasing evidence shows that abnormal microRNA (miRNA) expression is involved in GC tumorigenesis, but the role of specific miRNAs involved in this disease remains elusive. MiR-141 was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in GC are largely unclear. Here we found that the expression of miR-141 was significantly reduced in GC compared with paired adjacent normal tissues and was significantly correlated with a more aggressive phenotype of GC in patients. Ectopic expression of miR-141 mimics in GC cell lines resulted in reduced proliferation, invasion and migration, and inhibition of miR-141 in GC cell lines promoted cell proliferation, invasion and migration in vitro . We further demonstrated that miR-141 acted as tumor suppressors through targeting transcriptional co-activator with PDZ-binding motif (TAZ) in GC. Moreover, the inverse relationship between miR-141 and its target was verified in patients and xenograft mice. Finally, overexpression of miR-141 suppressed tumor growth and pulmonary metastasis in nude mice. Take together, we identified that miR-141 is a potent tumor suppressor in the stomach, and its growth inhibitory effects are, in part, mediated through its downstream target gene, TAZ. These findings implied that miR-141 might be employed as novel prognostic markers and therapeutic targets of GC.