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01.12.2018 | Letter to the Editor | Ausgabe 1/2018 Open Access

Molecular Cancer 1/2018

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

Zeitschrift:
Molecular Cancer > Ausgabe 1/2018
Autoren:
Wei Huang, Wen-Tao Wang, Ke Fang, Zhen-Hua Chen, Yu-Meng Sun, Cai Han, Lin-Yu Sun, Xue-Qun Luo, Yue-Qin Chen
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12943-018-0768-2) contains supplementary material, which is available to authorized users.

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.
Zusatzmaterial
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
Literatur
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