miR-205 Inhibits Neuroblastoma Growth by Targeting cAMP-Responsive Element-Binding Protein 1.
miR-205 Inhibits Neuroblastoma Growth by Targeting cAMP-Responsive Element-Binding Protein 1.
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DOI：
10.3727/096504017x14974834436195
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发表时间：
2018-04-10
影响因子：
3.1
通讯作者：
Zhou Y
中科院分区：
文献类型：
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作者：
Chen S;Jin L;Nie S;Han L;Lu N;Zhou Y
越来越多的证据表明microRNA-205（miR-205）参与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）中的功能仍不清楚。在此，我们发现miR-205在人NB组织样品和细胞系中显著下调。miR-205在低分化NB组织和国际神经母细胞瘤分期系统晚期组织中的表达较低。此外，NB细胞中miR-205的恢复抑制增殖、迁移和侵袭，并在体外诱导细胞凋亡，以及在体内损害肿瘤生长。cAMP反应元件结合蛋白1（CREB 1）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CREB 1的表达，并且CREB 1靶向BCL-2和MMP 9。CREB 1在人NB组织中也被发现上调，其表达与miR-205表达呈负相关（r =-0.554，p = 0.003）。重要的是，CREB 1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CREB 1在NB中发挥肿瘤抑制剂的作用。
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 (CREB1) 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 (r = −0.554, p = 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 CREB1.