RESEARCH ARTICLE Annexin-A1 Regulates MicroRNA-26b * and MicroRNA-562 to Directly Target NF-kB and Angiogenesis in Breast Cancer Cells

Annexin 1 (ANXA1) is an endogenous anti-inflammatory protein implicated in cancer. ANXA1 was previously shown to be regulated by hsa-miR-196a. However, whether ANXA1 itself regulates microRNA (miR) expression is unknown. Therefore, we investigated the regulation of miR by ANXA1 in MCF7 breast cancer cells. MCF7-EV (Empty vector) and MCF7-V5 (ANXA1-V5 expressing cells) were subjected to a miR microarray. Microarray analysis revealed a number of miRNAs which were dysregulated in MCF7-V5 cells. 2 novel miRNAs (miR562 and miR26b*) were validated, cloned and functionally characterized. As ANXA1 constitutively activates NF-kB activity to modulate breast cancer metastasis, we found that miR26b * and miR562 directly targeted the canonical NF-kB pathway by targeting the 39 UTR and inhibiting expression of Rel A (p65) and NF-kB1 (p105) respectively. MiR562 inhibited wound healing, which was reversed when ANXA1 was overexpressed. Overexpression of either miR562 or miR26b * in MCF-7 cells enhanced endothelial tube formation when cocultured with human umbilical cor