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.
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Abbreviations
- MMP-2/MMP-9:
-
Matrix metalloproteinase-2/matrix metalloproteinase-9
- CMM:
-
Choroid malignant melanoma
- miRNA:
-
MicroRNA
- lncRNA:
-
Long non-coding RNA
- FOXCUT:
-
FOXC1 promoter upstream transcript
- ECM:
-
Extracellular matrix
- ncRNAs:
-
Non-coding RNAs
- ISH:
-
In situ hybridization
- IHC:
-
Immunohistochemistry
- FCS:
-
Fetal calf serum
- FBS:
-
Fetal bovine serum
- NC mimic:
-
A negative control sequence
- RT:
-
Reverse transcription
- qPCR:
-
Quantitative PCR
- RAP:
-
RNA antisense purification
- CCK-8:
-
Cell Counting Kit-8
- FCM:
-
Flow cytometry assay
- SD:
-
Standard deviation
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X.W., Y.H., and J.C. wrote the paper and conceived and designed the experiments. Y.Z. analyzed the data. X.W. and Y.H. prepared the manuscript and revised it. L.C. is responsible for the guarantee of integrity of the entire study. All authors read and approved the final manuscript.
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Wang, X., Hu, Y., Cui, J. et al. Coordinated targeting of MMP-2/MMP-9 by miR-296-3p/FOXCUT exerts tumor-suppressing effects in choroidal malignant melanoma. Mol Cell Biochem 445, 25–33 (2018). https://doi.org/10.1007/s11010-017-3248-x
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DOI: https://doi.org/10.1007/s11010-017-3248-x