Circulating miR-221/222 reduces CD4+ T cells by inhibiting CD4 expression in colorectal cancer

Circulating miR-221/222 reduces CD4+ T cells by inhibiting CD4 expression in colorectal cancer
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循环中的 miR-221/222 通过抑制结直肠癌中的 CD4 表达来减少 CD4 T 细胞

DOI:
10.1093/abbs/gmab106
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发表时间:
2021-08-06
影响因子:
3.7
通讯作者:
Liu, Sanhong
Liu, Sanhong
中科院分区:
生物学3区
文献类型:
--
作者:
Hu, Jiajia;Zhang, Jiawei;Liu, Sanhong

文献摘要

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许多癌症患者的外周血中CD 4(+)水平较低。然而,其分子机制尚不清楚。在这里,我们发现miR-221和miR-222的血液水平在结直肠癌(CRC)患者中显著增加,循环miR-211和miR-222都是敏感的诊断标志物,曲线下面积分别为0.8790和0.9148。转染miR-221或miR-222导致表面CD 4抗原水平降低,但不导致表面CD 8抗原水平降低。荧光素酶报告基因分析显示miR-221/222直接调节人原代T细胞中的CD 4表达。这些数据表明,miR-221/222水平在CRC患者的血液中上调,并且miR-221/222抑制人原代T细胞中CD 4的表达。这些发现为调节血液中CD 4(+)T细胞的数量并进一步调整适合免疫治疗的微环境提供了一种新策略。
Many patients with cancers have low levels of CD4(+) in their peripheral blood. However, the molecular mechanism is still unclear. Here, we found that the blood levels of miR-221 and miR-222 were dramatically increased in patients with colorectal cancer (CRC), and both circulating miR-211 and miR-222 served as sensitive diagnostic markers with an area under the curve of 0.8790 and 0.9148, respectively. Transfection of either miR-221 or miR-222 resulted in the reduction of the surface CD4 antigen level but not the surface CD8 antigen level. The luciferase reporter assay showed that miR-221/222 directly regulated CD4 expression in human primary T cells. These data showed that miR-221/222 levels were upregulated in the blood of patients with CRC and that the expression of CD4 in human primary T cells was inhibited by miR-221/222. These findings provide a novel strategy for modulating the number of CD4(+) T cells in the blood and further adjusting the microenvironment suitable for immunotherapy.