Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C.

Gastric cancer is the fourth most common cancer and the second leading cause of cancer mortality worldwide but the underlying molecular mechanism is not entirely clear. The objective of this study was to explore the role of let-7a microRNA (miRNA) in gastric tumorigenesis and the possible correlation between RAB40C and let-7a miRNA in gastric cancer. We found that expression of let-7a is reduced in human gastric cancer tissues and cell lines and there was a significant correlation between the level of let-7a expression and the stage of differentiation. Overexpression of let-7a resulted in a decrease in cell proliferation and G(1) arrest, significantly suppressed anchorage-dependent growth in vitro and the tumorigenicity of gastric cancer cells in a nude mouse xenograft model. Furthermore, we demonstrated that RAB40C is regulated directly by let-7a and plays an essential role as a mediator of the biological effects of let-7a in gastric tumorigenesis. This study revealed that let-7a is significant in suppressing gastric cancer growth in vivo and in vitro and provided the first evidence that RAB40C is negatively regulated by let-7a at the posttranscriptional level via binding to the 3'-untranslated region of RAB40C messenger RNA in gastric cancer. The results of this study suggest that let-7a and RAB40C are potentially useful targets for gastric cancer diagnosis and therapy.