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MIR-708 promotes phagocytosis to eradicate T-ALL cells by targeting CD47.

ABSTRACT: Immunoevasion is a hallmark of cancer progression, and immune checkpoint blockade has emerged as a promising strategy for cancer treatment. microRNAs (miRNAs) are important negative regulators of gene expression in the immune system. Here, we demonstrate that miR-708 regulates CD47, a transmembrane protein that inhibits phagocytosis in T cell acute lymphoblastic leukemia. miR-708 directly targeted CD47 through binding to 3'UTR and is inversely correlated with CD47 expression. Functional studies showed that restoration of miR-708 expression in the T-ALL cell line is sufficient to promote phagocytosis by macrophages in the absence or presence of the anti-CD47 antibody to eradicate T-ALL cells, and inhibited tumor engraftment in vivo. Together, our findings suggest that miR-708 is a key negative regulator of CD47 and may serve as an attractive candidate for immunotherapy of T-ALL.

SUBMITTER: Huang W

PROVIDER: S-EPMC5782377 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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MIR-708 promotes phagocytosis to eradicate T-ALL cells by targeting CD47.

Huang Wei W Wang Wen-Tao WT Fang Ke K Chen Zhen-Hua ZH Sun Yu-Meng YM Han Cai C Sun Lin-Yu LY Luo Xue-Qun XQ Chen Yue-Qin YQ

Molecular cancer 20180124 1

Immunoevasion is a hallmark of cancer progression, and immune checkpoint blockade has emerged as a promising strategy for cancer treatment. microRNAs (miRNAs) are important negative regulators of gene expression in the immune system. Here, we demonstrate that miR-708 regulates CD47, a transmembrane protein that inhibits phagocytosis in T cell acute lymphoblastic leukemia. miR-708 directly targeted CD47 through binding to 3'UTR and is inversely correlated with CD47 expression. Functional studies ...[more]

PMID: 29368647

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