Multiple Tumor-Associated MicroRNAs Modulate the Survival and Longevity of Dendritic Cells by Targeting YWHAZ and Bcl2 Signaling Pathways

Tumors use a wide array of immunosuppressive strategies, such as reducing the longevity and survival of dendritic cells (DCs), to diminish immune responses and limit the effect of immunotherapy. In this study, we found that tumors upregulate the expression of multiple microRNAs (miRNAs), such as miR-16-1, miR-22, miR-155, and miR-503. These tumor-associated miRNAs influenced the survival and longevity of DCs by affecting the expression of multiple molecules that are associated with apoptotic signaling pathways. Specifically, miR-22 targeted YWHAZ to interrupt the PI3K/Akt and MAPK signaling pathways, and miR-503 downregulated Bcl2 expression. The result of the increased expression of miR-22 and miR-503 in the tumor-associated DCs was their reduced survival and longevity. Thus, tumor-associated miRNAs can target multiple intracellular signaling molecules to cause the apoptosis of DCs in the tumor environment. Use of miR-22 and miR-503 as inhibitors may therefore represent a new strategy to improve DC-based immunotherapies against tumors.