Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.
Department of Neurosurgery, Children's Hospital of Fudan University, Shanghai, China.
Cell Death Dis. 2020 Jun 1;11(6):408. doi: 10.1038/s41419-020-2621-y.
Exosomes are an important carrier for cell communication. miRNAs in exosomes are potential biomarkers and therapeutic targets in different types of cancer. However, the role of exosomal miRNAs in medulloblastoma (MB) patients is largely unknown. In this study, we reported that there was a higher level of miR-130b-3p in exosomes derived from MB patient plasma compared with exosomes from healthy control plasma. Exosomes from MB patient plasma could transfer miR-130b-3p to an MB cell line and played suppressor roles for cell proliferation. miR-130b-3p suppressed MB tumorigenesis by targeting a previously unknown target, serine/threonine-protein kinase 1 (SIK1), through the p53 signaling pathways. In addition, we found an unreported role of SIK1 in promoting MB tumor growth and an SIK1 inhibitor could inhibit MB cell proliferation. This research provides new insight into the molecular mechanism of MB and may provide a new therapeutic strategy for MB treatment.
外泌体是细胞通讯的重要载体。外泌体中的 miRNAs 是不同类型癌症中潜在的生物标志物和治疗靶点。然而，外泌体 miRNAs 在髓母细胞瘤 (MB) 患者中的作用在很大程度上尚不清楚。在这项研究中，我们报告说，与来自健康对照血浆的外泌体相比，来自 MB 患者血浆的外泌体中 miR-130b-3p 的水平更高。MB 患者血浆来源的外泌体可以将 miR-130b-3p 转移到 MB 细胞系中，并发挥抑制细胞增殖的作用。miR-130b-3p 通过 p53 信号通路靶向以前未知的靶标丝氨酸/苏氨酸蛋白激酶 1 (SIK1)，从而抑制 MB 肿瘤发生。此外，我们发现 SIK1 在促进 MB 肿瘤生长中具有未被报道的作用，并且 SIK1 抑制剂可以抑制 MB 细胞增殖。这项研究为 MB 的分子机制提供了新的见解，并可能为 MB 的治疗提供新的治疗策略。
