Neuroblastoma (NB) is a heterogeneous tumor that is common in infants and young children. Long non-coding RNA X-inactive specific transcript (XIST) is implicated in NB advancement. Nevertheless, the role and regulatory mechanism by which XIST in NB are not fully elucidated. Expression levels of XIST, microRNA-375-5p (miR-375), and L1 cell adhesion molecular (L1CAM) were examined through quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, proliferation, and colony formation of NB cells were determined with flow cytometry, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), or cell colony formation assays. Cell apoptotic rate was detected with flow cytometry assay. The relationship between XIST or L1CAM and miR-375 was verified via dual-luciferase reporter assay. The level of L1CAM protein was examined through western blotting. The role of XIST in vivo was confirmed through xenograft assay. XIST and L1CAM were upregulated while miR-375 was downregulated in NB tissues and cells. XIST depletion repressed tumor growth in vivo and elevated radiosensitivity, arrested cell cycle progression, and impeded proliferation of NB cells in vitro. Mechanistically, XIST modulated L1CAM expression through competitively binding to miR-375. Furthermore, miR-375 inhibitor recovered XIST inhibition-mediated effects on the radiosensitivity and malignant behaviors of NB cells. Also, L1CAM overexpression reversed the effects of miR-375 enhancement on the cell cycle progression, proliferation, and radiosensitivity of NB cells. XIST downregulation repressed tumor growth and boosted radiosensitivity of NB via modulating the miR-375/L1CAM axis, indicating that XIST was a promising target for NB treatment.

神经母细胞瘤 (NB) 是一种异质性肿瘤，常见于婴幼儿。长非编码 RNA X 非活性特异性转录本 (XIST) 与 NB 进展有关。然而，XIST 在 NB 中的作用和调节机制尚未完全阐明。通过定量实时聚合酶链反应 (qRT-PCR) 检查 XIST、microRNA-375-5p (miR-375) 和 L1 细胞粘附分子 (L1CAM) 的表达水平。NB 细胞的细胞周期进程、增殖和集落形成通过流式细胞术、3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) 或细胞集落形成测定来确定。流式细胞仪检测细胞凋亡率。XIST 或 L1CAM 与 miR-375 之间的关系通过双荧光素酶报告基因测定得到验证。通过蛋白质印迹检查L1CAM蛋白的水平。XIST 在体内的作用通过异种移植试验得到证实。XIST 和 L1CAM 上调，而 miR-375 在 NB 组织和细胞中下调。XIST 耗竭抑制体内肿瘤生长并提高放射敏感性，阻止细胞周期进程，并在体外阻碍 NB 细胞的增殖。从机制上讲，XIST 通过与 miR-375 竞争性结合来调节 L1CAM 的表达。此外，miR-375 抑制剂恢复了 XIST 抑制介导的对 NB 细胞放射敏感性和恶性行为的影响。此外，L1CAM 过表达逆转了 miR-375 增强对 NB 细胞的细胞周期进程、增殖和放射敏感性的影响。