Coordinated targeting of MMP-2/MMP-9 by miR-296-3p/FOXCUT exerts tumor-suppressing effects in choroidal malignant melanoma.

Abstract

Choroidal melanoma is the most common intraocular tumor in adults, and overexpression of matrix metalloproteinase-2 or matrix metalloproteinase-9 (MMP-2/MMP-9) is associated with angiogenesis and tumor metastasis of the choroidal malignant melanoma (CMM). This study aims to investigate the functions and mechanisms of microRNA or long non-coding RNA-targeted MMP-2/MMP-9 in CMM. We demonstrated that expressions of MMP-2/MMP-9 were increased in CMM tissues and C918 cells in comparison with normal choroidal melanocytes. Bio-informatics prediction and our experiments validated that MMP-2 and MMP-9 were simultaneously targeted by miR-296-3p and FOXC1 promoter upstream transcript (FOXCUT); the latter two exerted tumor-suppressing effects on CMM cells by inhibiting cell proliferation, cell cycle progression, migration, invasion, and induction of cell apoptosis. Furthermore, significant downregulations of miR-296-3p and FOXCUT were found in C918 cells compared with choroidal melanocytes from the unaffected eyes, and a positive correlation was observed between their levels in three cases of eye malignant melanomas. Our data indicated that MMP-2/MMP-9 was coordinately targeted by two non-coding RNAs, miR-296-3p and FOXCUT, which were decreased, and tumor-suppressing factors in CMM. Further study will show the possibility of developing them as therapeutic candidates for CMM.