Sulforaphane suppresses autophagy during the malignant progression of gastric carcinoma via activating miR-4521/PIK3R3 pathway

Abstract

Objective: Sulforaphane, which exerts an effective anti-cancer ability, is a phytochemical converted from cruciferous plants. Here, we aimed to identify whether sulforaphane could suppress autophagy during the malignant progression of gastric carcinoma and to explore the underlying mechanisms.

Methods: SGC7901 cells were transfected with miR-4521 mimics, inhibitor, and pcDNA3.1-PIK3R3, and treated with sulforaphane or autophagy inhibitor. Cell proliferation, apoptosis, and miR-4521 or PIK3R3 expression were detected.

Results: MiR-4521 over-expression suppressed LC3-II/I ratio and Beclin-1 expression but induced p62 expression in SGC7901 cells. MiR-4521 also reduced gastric carcinoma cell proliferation and promoted apoptosis in vitro. In the mechanical observation, we identified that miR-4521 directly targeted PIK3R3 to repress its expression, and PIK3R3 up-regulation partly antagonized miR-4521-mediated autophagy, proliferation, and apoptosis in gastric carcinoma cells. In addition, sulforaphane exerted effective anti-cancer functions by repressing autophagy and growth in tumor cells at a concentration-dependent way. MiR-4521 inhibition or PIK3R3 over-expression weakened the anti-cancer functions of sulforaphane in gastric carcinoma cells.

Conclusion: Consequently, miR-4521 suppressed autophagy during the malignant progression of gastric carcinoma by targeting PIK3R3. Thus, miR-4521 may be applied as a therapeutic target for sulforaphane in gastric carcinoma.

Keywords: PIK3R3; Sulforaphane; autophagy; gastric carcinoma; miR-4521.