MIR-184 INHIBITS PROLIFERATION AND INVASION OF GASTRIC CANCER CELLS BY TARGETING STC2

Qing Qiao^#, Jia-Xing He^#, Ke Wang, Shuai Zhou, Ling Dang,  Bo Zhang^*, Nan Wang^*

Department of General Surgery, Tangdu Hospital, the Air Force Medical University, Xi’an 710038, China

Objective: To investigate the regulatory mechanism of miR-184 in blocking gastric cancer (GC) progression through targeting stanniocalcin 2 (STC2). 

Methods: Data analysis was performed on clinical samples in the dataset GSE63121 and the UALCAN database, and the expression levels of miR-184 and STC2 in GC patients were calculated. Over- or low-expression cell strains of miR-184 and STC2 were established by cell transfection of miR-184 mimics, miR-184 inhibitors, STC2 plasmids, and STC2 siRNA, respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of miR-184 and STC2 in GC cell lines. The expression of STC2 was detected by Western blot. The MTT and transwell methods were used to detect cell proliferation and invasion. In addition, the target binding sequence for binding miR-184 to STC2 was predicted from the Targetscan database, and a double luciferase reporter experiment was used to confirm the binding site on STC2. 

Results: The expression of miR-184 was significantly down-regulated in gastric cancer patients and the expression of STC2 was significantly up-regulated in both GC cell lines. MiR-184 overexpression significantly inhibited the expression of STC2 in MGC803 GC cells and functionally inhibited the proliferation and invasion of MGC803 cells. Whereas, miR-184 low-expressing MGC803 GC cells showed the opposite results. The proliferation and invasion ability of low-expressing MGC803 cells was significantly reduced. The double luciferase reporter gene experiment and Western blotting results showed that miR-184 could directly and negatively regulate the expression of STC2. In addition, overexpression of STC2 completely reversed the inhibitory effect of miR-184 on GC cells. 

Conclusions: Th results indicate that miR-184 can inhibit the proliferation and invasion of GC cells by targeting STC2 in GC, thus providing a new therapeutic target for GC.