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The importance of non-coding RNA transcripts in regulating microRNA (miRNA) functions, especially the 3′-untranslated region (3′ UTR), has been revealed in recent years. Genes encoding the extracellular matrix normally produce large mRNA transcripts including the 3′ UTR. How these large transcripts affect miRNA functions and how miRNAs modulate extracellular matrix protein expression are largely unknown. Here, we demonstrate that the overexpression of the CD44 3′ UTR results in enhanced cell motility, invasion and cell adhesion in human breast carcinoma cell line MDA-MB-231. Furthermore, we found that expression of the CD44 3′ UTR enhances metastasis in vivo. We hypothesize that increased expression of the CD44 3′ UTR affects miRNA binding and modulates synthesis of the extracellular matrix. Computational analysis indicated that miRNAs that interact with the CD44 3′ UTR also …