miR-409-3p inhibits HT1080 cell proliferation, vascularization and metastasis by targeting angiogenin.

Although the expression of angiogenin (ANG), an angiogenic and tumorigenic factor, is elevated in various types of cancers, its regulation mechanism remains unclear. In the present study, in silico search predicted that miR-409-3p targeted to the 3' untranslated region (3'UTR) of the ANG mRNA. Overexpression of miR-409-3p in fibrosarcoma HT1080 cells resulted in decreased steady-state level of ANG transcript and ANG production which were achieved through direct binding of this miRNA to the ANG 3'UTR. The suppressions of miR-409-3p to rRNA transcription, cell proliferation and vasculogenic mimicry could be partially restored by overexpression of ANG with a mutated binding site of miR-409-3p within the ANG 3'UTR. Ectopic expression of miR-409-3p in transplanted HT1080 cells led to the retardation of tumor growth, vascularization and lung metastasis in mouse tumor xenografts. In these xenografts tissues, the expression of miR-409-3p displayed an inverse correlation with ANG, which was also detected in human fibrosarcoma samples. In addition, the suppression effects of miR-409-3p on cell proliferation and angiogenesis in vitro were also found in human umbilical vein endothelial cells. Taken together, these data demonstrate that miR-409-3p inhibits tumor growth, vascularization and metastasis through down-regulating ANG expression.