MicroRNA-222 is a potential target for developing blood-based diagnostic methods and treatment of malignant glioma

我们以前曾报道，在癌细胞中过表达的microRNA(MiR)-222下调ICAM-1，从而降低癌细胞对细胞毒性T淋巴细胞(CTL)的敏感性。在本研究中，我们发现miR-222在一些人脑胶质瘤组织中表达上调。抑制miR-222可恢复脑胶质瘤细胞系ICAM-1的表达，恢复其对CTL介导的细胞毒作用的敏感性。因此，miR-222表达的增加可能有助于胶质瘤逃避宿主的免疫监视。随后我们发现，定量聚合酶链式反应可以在脑胶质瘤患者的血清中检测到miR-222。此外，miR-222的高表达与患者的疾病进展和预后不良有关，提示有可能开发新的诊断方法来判断胶质瘤的恶性特征和患者的预后。有趣的是，含有胶质瘤细胞分泌的外切体的miR-222可以被树突状细胞(DC)摄取，并降低DC上ICAM-1的表达，这对T细胞的激活是重要的。这些结果表明miR-222可能成为开发胶质瘤患者新的诊断和治疗方法的潜在靶点。

We previously reported that microRNA(miR)-222 over-expressed in cancer cells down-regulates ICAM-1, thereby reducing cancer cell susceptibility to cytotoxic T lymphocytes(CTLs). In this study, we found that miR-222 was up-regulated in some of human glioma tissues. Inhibition of miR-222 led to recovery of ICAM-1 expression in glioma cell lines, resulting in restoration of their susceptibility to CTL-mediated cytolysis. Thus, the increased miR-222 expression may contribute to glioma escape from the host immune surveillance. We then found that miR-222 could be detected by quantitative PCR in serum of glioma patients. Moreover, the elevated miR-222 expression was associated with disease progression and poor prognosis of the patients, suggesting possible development of new diagnostic methods for malignant characteristics of glioma and prognosis of the patients. Interestingly, miR-222 containing exosomes secreted from glioma cells may be uptaken by dendritic cells(DCs), and decreased ICAM-1 expression on DC, which is important for T cell activation. These results indicate that miR-222 may be a potential target for developing novel diagnostic and therapeutic methods for glioma patients.