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miR-205 通过靶向 cAMP 反应元件结合蛋白 1 抑制神经母细胞瘤生长。

miR-205 Inhibits Neuroblastoma Growth by Targeting cAMP-Responsive Element-Binding Protein 1.

机构信息

Department of Thoracic Surgery, The Second Hospital of Jilin UniversityChangchunP.R. China.

Department of Pediatrics, The First Hospital of Jilin UniversityChangchunP.R. China.

出版信息

Oncol Res. 2018 Apr 10;26(3):445-455. doi: 10.3727/096504017X14974834436195. Epub 2017 Jun 26.

Abstract

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 .

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3580/7844742/8120688defae/OR-26-445-g001.jpg

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