Department of Thoracic Surgery, The Second Hospital of Jilin UniversityChangchunP.R. China.
Department of Pediatrics, The First Hospital of Jilin UniversityChangchunP.R. China.
Oncol Res. 2018 Apr 10;26(3):445-455. doi: 10.3727/096504017X14974834436195. Epub 2017 Jun 26.
Accumulating evidence indicates that microRNA-205 (miR-205) is involved in tumor initiation, development, and metastasis in various cancers. However, its functions in neuroblastoma (NB) remain largely unclear. Here we found that miR-205 was significantly downregulated in human NB tissue samples and cell lines. miR-205 expression was lower in poorly differentiated NB tissues and those of advanced International Neuroblastoma Staging System stage. In addition, restoration of miR-205 in NB cells suppressed proliferation, migration, and invasion and induced cell apoptosis in vitro, as well as impaired tumor growth in vivo. cAMP-responsive element-binding protein 1 () was identified as a direct target gene of miR-205. Expression of an miR-205 mimic in NB cells significantly diminished expression of CREB1 and the CREB1 targets BCL-2 and MMP9. CREB1 was also found to be upregulated in human NB tissues, its expression being inversely correlated with miR-205 expression ( = -0.554, = 0.003). Importantly, CREB1 upregulation partially rescued the inhibitory effects of miR-205 on NB cells. These findings suggest that miR-205 may function as a tumor suppressor in NB by targeting .
越来越多的证据表明，微小 RNA-205（miR-205）参与了多种癌症的肿瘤发生、发展和转移。然而，其在神经母细胞瘤（NB）中的作用在很大程度上仍不清楚。在这里，我们发现 miR-205 在人 NB 组织样本和细胞系中表达显著下调。miR-205 在低分化 NB 组织和国际神经母细胞瘤分期系统晚期的组织中表达水平较低。此外，miR-205 在 NB 细胞中的恢复表达抑制了体外的增殖、迁移和侵袭，并诱导了细胞凋亡，同时也损害了体内的肿瘤生长。环磷酸腺苷反应元件结合蛋白 1（CREB1）被鉴定为 miR-205 的直接靶基因。miR-205 模拟物在 NB 细胞中的表达显著降低了 CREB1 及其靶基因 BCL-2 和 MMP9 的表达。在人 NB 组织中也发现 CREB1 上调，其表达与 miR-205 表达呈负相关（ = -0.554， = 0.003）。重要的是，CREB1 的上调部分挽救了 miR-205 对 NB 细胞的抑制作用。这些发现表明，miR-205 可能通过靶向 发挥抑癌作用，从而在 NB 中发挥作用。
