Abstract

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.

中文翻译：

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循环 miR-221/222 通过抑制结肠直肠癌中的 CD4 表达来减少 CD4+ T 细胞

摘要

许多癌症患者的 CD4 ^{+水平较低}在他们的外周血中。然而，分子机制仍不清楚。在这里，我们发现 miR-221 和 miR-222 的血液水平在结直肠癌 (CRC) 患者中显着增加，并且循环 miR-211 和 miR-222 都作为敏感的诊断标志物，其曲线下面积为分别为 0.8790 和 0.9148。转染 miR-221 或 miR-222 会导致表面 CD4 抗原水平降低，但不会降低表面 CD8 抗原水平。荧光素酶报告基因检测显示 miR-221/222 直接调节人原代 T 细胞中的 CD4 表达。这些数据表明 miR-221/222 水平在 CRC 患者的血液中上调，并且人原代 T 细胞中 CD4 的表达被 miR-221/222 抑制。这些发现提供了一种调节 CD4 数量的新策略⁺血液中的 T 细胞，进一步调整适合免疫治疗的微环境。