miR-125a and let-7e inhibit IL-6 signaling by directly targeting the IL-6, IL-6R and STAT3 genes in HUVECs. (A) IL-6 mRNA expression in response to overexpression of miR-125a or let-7e mimics, or inhibition of miR-125a or let-7e with anti-miRs in HUVECs. (B) Effect of let-7e overexpression on the luciferase reporter containing either the wild-type or mutagenized 3′UTR of the human IL-6 gene in HEK-293 cells. Luciferase activity for constructs with the wild-type (WT) and mutant (MT) 3′UTR sequences. (C, D) IL-6R and STAT3 expression in response to overexpression of miR-125a or let-7e mimics, or inhibition of miR-125a or let-7e with anti-miRs in HUVECs. (E) Effect of miR-125a or let-7e overexpression on the luciferase reporter containing either the wild-type or mutagenized 3′UTR of the human IL-6R or STAT3 gene in HEK-293 cells. Luciferase activity for constructs with the WT and MT 3′UTR constructs. (F) STAT3 phosphorylation in response to IL-6 (100 ng/ml) in HUVECs with concurrent overexpression of miR-125a or let-7e. *P < 0.05, **P < 0.01, ***P < 0.001 compared to controls. Error bars, s.e.m.
