MicroRNA-597-3p targets MACC1 to suppress proliferation and invasion of human ovarian cancer cells
Background
Ovarian cancer is a lethal gynecological malignancy, largely due to late-stage diagnosis and poor prognosis. MicroRNA-597-3p (miR-597-3p) has been identified as a tumor suppressor in several cancers, while metastasis-associated colon cancer 1 (MACC1) functions as an oncogene that promotes metastasis. This study investigated the role of miR-597-3p and its regulation of MACC1 in ovarian cancer progression.
Methods
Ovarian cancer cell lines and the normal ovarian epithelial cell line IOSE-398 were used. Quantitative real-time PCR (qRT-PCR) measured the expression of miR-597-3p and MACC1. Functional assays (MTT, colony formation, AO/EB staining, and Transwell invasion) evaluated cell proliferation, cell death, and invasion. Dual-luciferase reporter assays confirmed the interaction between miR-597-3p and MACC1, while bioinformatics analysis identified potential targets. Western blotting was used to validate MACC1 and downstream proteins, MMP-2, and MMP-9 at the protein level.
Results
MiR-597-3p was significantly downregulated ( P < 0.05) in ovarian cancer cells, whereas MACC1 was upregulated. Overexpression of miR-597-3p suppressed cell viability, colony formation, and invasion, and increased cell death with a pro-apoptotic shift in Bax/Bcl-2 expression. Mechanistically, miR-597-3p directly targeted MACC1, leading to reduced expression of MMP-2 and MMP-9 at both transcript and protein levels. Notably, MACC1 overexpression reversed the tumor-suppressive effects of miR-597-3p.
Conclusions
MiR-597-3p functions as a tumor suppressor in ovarian cancer by directly targeting MACC1, thereby inhibiting proliferation, invasion, and survival. These findings highlight the miR-597-3p/MACC1 axis as a potential therapeutic target and suggest miR-597-3p as a promising biomarker for ovarian cancer.