RESUMO
OBJECTIVE: MicroRNAs are widely thought to play a regulatory role in gene expression. Although the more unique microRNA expression profiles have been reported in several tumors, there remains a scarcity of knowledge in relation to microRNA expression profiles in GISTs. During this study, through the alteration in the expression of microRNA-152 (miR-152) in gastrointestinal stromal tumor (GIST) cells, we subsequently evaluated its ability to influence the processes associated with cancer, including proliferation, migration, invasion, and apoptosis, as well as the associated mechanisms. METHODS: The expression of miR-152 and cathepsin L (CTSL) in GIST cell lines (GIST882, GIST430, GIST48 and GIST-T1) and normal gastric mucosal cell line RGM-1 were determined. A series of miR-152 mimics, miR-152 inhibitors, and siRNA against CTSL were introduced to treat GIST-T1 cells with the lowest miR-152 and the highest CTSL were assessed. Cell viability, cell cycle entry, apoptosis, and cell migration/invasion were all evaluated by means of CCK-8 assay, flow cytometry analyses of Annexin V-FITC/PI staining, and transwell assays. RESULTS: The target prediction program and luciferase reporter gene assay verified CTSL is the target of miR-152. Regarding the biological significance of miR-152, siRNA knockdown and ectopic expression studies revealed that miR-152 mimic or siRNA against CTSL exposure reduced cell viability and migration/invasion, which resulted in more cells arrested at the S stage, and induced apoptosis. MiR-152 inhibitor exposure was observed to have induced effects on CTSL cells as opposed to those induced by that of the miR-152 mimics. In contrast, miR-152 downregulation abrogated the effects induced by siRNA against CTSL treatment. CONCLUSION: The key findings of this study provided evidence suggesting that miR-152 functions by means of binding to CTSL to induce GIST cell apoptosis and inhibit proliferation, migration, and invasion. The anti-tumor role of miR-152 makes it an attractive therapeutic target for GIST.
