Dual-Functions of miR-373 and miR-520c by Differently Regulating the Activities of MMP2 and MMP9

MicroRNA-520c (miR-520c) and microRNA-373 (miR-373) are originally characterized as both oncogenes and tumor suppressors in different types of human cancers. In this study, we found that translation of mRNA of MT1-MMP, an oncogene related to tumor metastasis, was well inhibited by miR-520c and miR-373 in several types of human cancer cells. Our experimental data demonstrated that these two microRNAs inhibited the translation of mRNA of MT1-MMP and down-regulated its proteolytic enzyme activities via targeting 3'UTR of mRNA of MT1-MMP, further decreased activating proMMP2 into active MMP2 in fibrosarcoma HT1080, benign prostatic hyperplasia epithelial cell BPH-1 and glioblastoma U87GM. More interestingly, from the effects of microRNAs on cell functions, we found that cell growth were all blocked on fibronectin and type IV collagen coated plates and also in three-dimension type I collagen lattice but enhanced only in HT1080 cells on type IV collagen coated plates and in three-dimension type I collagen lattice; cell migration results showed the same effect as that of cell growth. The difference was due to up-regulating the expression of MMP9 gene by miR-520c and miR-373 in HT1080 cells but not in BPH-1 and U87GM cells. Our findings suggest that miR-520c and miR-373, which have different roles in different type of cancer via regulating the translation of mRNA of MT1-MMP and the expression of MMP9 gene, might have an important clue on clinic when selecting the therapeutic regimen and finding new drugs for intervention in different kinds of cancer.