Department of Pediatric Intensive Care Unit (PICU), The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
IUBMB Life. 2020 Dec;72(12):2627-2636. doi: 10.1002/iub.2392. Epub 2020 Oct 8.
Emerging evidence has demonstrated the crucial roles of long noncoding RNAs in human cancers, including neuroblastoma (NB). DLX6 antisense RNA 1 (DLX6-AS1) has been identified as an oncogenic driver in NB. However, the mechanisms of DLX6-AS1 in NB progression are not fully understood. Our data showed that DLX6-AS1 was significantly overexpressed in NB tissues and cells. Moreover, DLX6-AS1 silencing repressed NB cell viability, colony formation, migration, and invasion, and promoted cell cycle arrest and apoptosis in vitro, as well as decreased tumor growth in vivo. Mechanistically, DLX6-AS1 operated as a miR-513c-5p sponge. MiR-513c-5p mediated the regulation of DLX6-AS1 on NB cell malignant progression in vitro. PLK4 was a target of miR-513c-5p- and DLX6-AS1-controlled PLK4 expression via sponging miR-513c-5p. Furthermore, the suppressive effect of miR-513c-5p overexpression on NB cell malignant progression in vitro was reversed by PLK4 upregulation. Our findings identified a novel regulatory mechanism, the DLX6-AS1/miR-513c-5p/PLK4 axis, in NB progression, highlighting a strong rationale for developing DLX6-AS1 as a new target for NB management.
越来越多的证据表明,长非编码 RNA 在人类癌症中(包括神经母细胞瘤[NB])发挥着关键作用。DLX6 反义 RNA 1(DLX6-AS1)已被确定为 NB 中的致癌驱动因子。然而,DLX6-AS1 在 NB 进展中的机制尚不完全清楚。我们的数据显示,DLX6-AS1 在 NB 组织和细胞中显著过表达。此外,DLX6-AS1 沉默抑制了 NB 细胞的活力、集落形成、迁移和侵袭,促进了细胞周期停滞和细胞凋亡,并在体内减少了肿瘤生长。机制上,DLX6-AS1 作为 miR-513c-5p 的海绵。miR-513c-5p 介导了 DLX6-AS1 在体外对 NB 细胞恶性进展的调节。PLK4 是 miR-513c-5p 和 DLX6-AS1 调控的 PLK4 表达的靶标,通过海绵吸附 miR-513c-5p。此外,miR-513c-5p 过表达对 NB 细胞恶性进展的抑制作用在体外被 PLK4 上调所逆转。我们的研究结果确定了一个新的调控机制,即 DLX6-AS1/miR-513c-5p/PLK4 轴,在 NB 进展中发挥作用,这为将 DLX6-AS1 作为 NB 管理的新靶点提供了强有力的依据。