Visfatin promotes the malignancy of human acute myeloid leukemia cells via regulation of IL-17.

Understanding the mechanisms of malignancy in acute myeloid leukemia (AML) cell is important for the targeted treatment and drug development. We found that visfatin, a 52-kDa adipokine, can positively regulate the proliferation of AML cells. Targeted inhibition of visfatin via its specific siRNAs or inhibitor can suppress the proliferation of AML cells. Further, knockdown of visfatin can increase the doxorubicin (Dox) and cisplatin (CDDP) sensitivity of AML cells. Among the tested six cytokines, si-visfatin can decrease the expression of interleukin-17 (IL-17). Over expression of IL-17 can reverse si-visfatin suppressed cell proliferation and increased Dox sensitivity. The upregulation of IL-17 was also involved in visfatin induced activation of PI3K/Akt signals in AML cells. The inhibitor of PI3K/Akt can synergistically suppress the proliferation of HL60 cells which were transfected with si-visfatin. Knockdown of visfatin can increase the expression of miR-135a, which can bind to the 3'UTR of IL-17 and decrease its expression. The inhibitor of miR-135a can attenuate si-visfatin suppressed expression of IL-17 and proliferation of AML cells. Collectively, our data suggested that visfatin can increase the malignancy of AML cells via regulation of miR-135a/IL-17/PI3K/Akt signals.