Background: Increasing evidences have documented that microRNAs (miRNAs) act as oncogenes or tumor suppressors in gastric cancer (GC). In this study, we aimed to investigate the expression of miR-133b in a large number of GC samples and elucidate its role in GC carcinogenesis and the detailed mechanism.
Methods: We used Taqman probe stem-loop real-time PCR to accurately measure the levels of miR-133b in 100 pairs of gastric cancer tissues and the adjacent non-neoplastic tissues. miR-133b mimics were overexpressed in GC cell lines, miR-133b inhibitors were also introduced in GES cells to investigate its role on regulating cell proliferation, cell migration and cell invasion. The target of miR-133b was identified by luciferase reporter assay and western blot. Fascin actin-bundling protein 1 (FSCN1) siRNA was used to achieve the knockdown of FSCN1 in GC cells and to investigate its role on modulating GC cell proliferation and invasion.
Results: miR-133b was significantly down-regulated in GC cell lines and in GC tissues compared with adjacent normal tissues. Moreover, lower-level of miR-133b was also associated with venous invasion and a more aggressive tumor phenotype. Re-introduction of miR-133b in GC cells can inhibit cell proliferation, cell migration and invasion. In contrary, knockdown of miR-133b in GES cells can promote cell proliferation and invasion. Further investigation indicated that miR-133b targeted FSCN1 in GC cells and knockdown of FSCN1 can also inhibit GC cell growth and invasion.
Conclusion: Our findings demonstrated that miR-133b was significantly down-regulated in GC tissues and exerted its tumor suppressor role in GC cells. The investigation of the detailed mechanism showed that miR-133b directly targeted FSCN1 which functioned as an oncogenic gene in GC cells. These results suggested that miR-133b can be developed as a new diagnostic marker or therapeutic target for GC.