The online version of this article (https://doi.org/10.1186/s12943-018-0768-2) contains supplementary material, which is available to authorized users.
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.
Additional file 1: Figure S1. (A-B). Jurkat cells were electroporated with mimics-NC and mimics-miR-708, The levels of miR-708 was assessed by qRT − PCR and normalized to U6.Cell lysates were prepared for western blotting with the antibody against CD47, and the expression of GAPDH served as a loading control. Figure S2. qRT-PCR analysis of the expressoion of miR-708 and CD47 in B-ALL. U6 and GAPDH were used as endogenous control. Figure S3. Apoptosis assay of CCRF-CEM and Jurkat upon transfection of miR-708 mimics or mimics-NC, respectively. Figure S4. Following the subcutaneous inoculation of CCRF-CEM-LV-NC and CCRF-CEM-LV-miR-708, the levels of miR-708 and CD47 were assessed by qRT − PCR and western blot, respectively.(A-B). Overexpressed miR-708 reduced tumor weight. Error bars reflect ±SEM (five mice, *, p < 0.05; **, p < 0.01).(C). (DOCX 30259 kb)12943_2018_768_MOESM1_ESM.docx
Additional file 2: Table S1. Characteristics of test cohort. (DOCX 14 kb)12943_2018_768_MOESM2_ESM.docx
Additional file 3: Materials and methods. (DOCX 22 kb)12943_2018_768_MOESM3_ESM.docx
Han BW, Feng DD, Li ZG, Luo XQ, Zhang H, Li XJ, Zhang XJ, Zheng LL, Zeng CW, Lin KY, et al. A set of miRNAs that involve in the pathways of drug resistance and leukemic stem-cell differentiation is associated with the risk of relapse and glucocorticoid response in childhood ALL. Hum Mol Genet. 2011;20:4903–15. CrossRefPubMedPubMedCentral
- MIR-708 promotes phagocytosis to eradicate T-ALL cells by targeting CD47
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