Department of Pediatrics, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
Eur Rev Med Pharmacol Sci. 2020 May;24(10):5526-5533. doi: 10.26355/eurrev_202005_21338.
Neuroblastoma is the most frequent tumor of sympathetic nervous system in infants. MiRNAs acted as oncogenes or tumor suppressors in the process of tumor development. We aim at exploring the functions of miRNA in neuroblastoma.
Cell viability and invasion were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assays. Western blot was utilized to assess the protein expression associated with epithelial-mesenchymal transition (EMT) markers. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to calculate the mRNA levels of miRNA and gene.
MiR-424 was downregulated while doublecortin like kinase 1 (DCLK1) was upregulated in neuroblastoma tissues and cells compared to adjacent non-tumor and normal spongiocyte cells. MiR-424 suppressed cell viability, invasion, and EMT by targeting DCLK1. MiR-424 regulated the expression of DCLK1 by directly binding to the 3'-untranslated region (UTR) of DCLK1 mRNA in SK-N-SH and Be2C cells. DCLK1 reversed partial functions of miR-424 in neuroblastoma.
MiR-424 suppressed cell viability, invasion, and EMT by directly targeting the 3'-UTR of DCLK1 mRNA. The newly identified miR-424/DCLK1 axis provides novel insights into the pathogenesis of neuroblastoma.
神经母细胞瘤是婴儿交感神经系统最常见的肿瘤。miRNA 在肿瘤发展过程中作为癌基因或肿瘤抑制因子发挥作用。我们旨在探讨 miRNA 在神经母细胞瘤中的功能。
通过细胞计数试剂盒-8（CCK-8）和 Transwell 分析评估细胞活力和侵袭。Western blot 用于评估与上皮-间充质转化（EMT）标志物相关的蛋白表达。定量实时聚合酶链反应（qRT-PCR）用于计算 miRNA 和基因的 mRNA 水平。
与相邻非肿瘤和正常海绵细胞相比，神经母细胞瘤组织和细胞中的 miR-424 下调，而双皮质激酶 1（DCLK1）上调。miR-424 通过靶向 DCLK1 抑制细胞活力、侵袭和 EMT。miR-424 通过直接结合 SK-N-SH 和 Be2C 细胞中 DCLK1 mRNA 的 3'-非翻译区（UTR）来调节 DCLK1 的表达。DCLK1 逆转了 miR-424 在神经母细胞瘤中的部分功能。
miR-424 通过直接靶向 DCLK1 mRNA 的 3'-UTR 抑制细胞活力、侵袭和 EMT。新鉴定的 miR-424/DCLK1 轴为神经母细胞瘤的发病机制提供了新的见解。
