An oncogenic role of miR-592 in tumorigenesis of human colorectal cancer by targeting Forkhead Box O3A (FoxO3A)

OBJECTIVE: A microRNA (miRNA) that functionally downregulates the expression of tumor suppressors can be defined as an oncomir. Here, we interrogate the biological significance of miR-592 in colorectal cancer (CRC). RESEARCH DESIGN AND METHODS: The expression of miR-592 in CRC tissues and cell lines was ascertained by qRT-PCR assay, and the expression of its target gene was determined by immunohistochemistry staining. The oncogenic role of miR-592 was assessed in terms of cell proliferation, migration, and clonogenicity in vitro, whereas the tumorigenicity was assessed by inhibiting endogenous miR-592 in CRC cells in vivo. RESULTS: A striking upregulation of miR-592 was observed in CRC tissues and cell lines compared to the matched adjacent non-tumor tissues and normal colon cells. Importantly, Forkhead Box O3A (FoxO3A) was identified as a novel target of miR-592. miR-592 inhibitor exhibited a significant reduction of migration, proliferation, and clonogenicity in CRC cells. These cells also displayed a decreased tumorigenicity in SCID mice relative to the control cells. CONCLUSION: These data suggest that miR-592 may promote the progression and metastasis, in part, by targeting FoxO3A in CRC. miR-592 may be a novel target for CRC treatment and antagomir-592 may inhibit the proliferation and metastasis of CRC cells.