Malignant glioma is an aggressive type of brain tumor with poor prognosis and mostly incurable. Although cisplatin is used for adjuvant chemotherapy against glioma, intrinsic and acquired resistance restricts the application of cisplatin. Long noncoding RNA (lncRNA) DANCR is reported to regulate the differentiation and progression of several cancers. However, whether DANCR participates in cisplatin resistance of glioma is still unknown. In this study, we found that DANCR expression was negatively correlated with cisplatin sensitivity in glioma cells. Gain-of and loss-of function assays revealed that DNACR attenuated cisplatin-induced cell proliferation inhibition in vitro and xenograft growth suppression in vivo. Furthermore, DNACR also attenuated cisplatin-induced cell apoptosis in vitro and in vivo. Mechanistically, we found that DANCR upregulated AXL via competitively binding miR-33a-5p, miR-33b-5p, miR-1-3p, miR-206, and miR-613. Through upregulating AXL, DANCR activated PI3K/Akt/NF-κB signaling pathway in glioma cells. Inhibiting AXL/PI3K/Akt/NF-κB signaling pathway reversed the effects of DANCR on cisplatin resistance. In conclusion, we identified a cisplatin-resistance associated lncRNA DANCR. DANCR promotes cisplatin resistance via activating AXL/PI3K/Akt/NF-κB signaling pathway in glioma. Our data suggested that DANCR would be a potential biomarker for predicting cisplatin sensitivity and a therapeutic target for enhancing cisplatin efficacy in glioma.

恶性神经胶质瘤是一种侵袭性的脑肿瘤，预后较差，大多无法治愈。尽管将顺铂用于针对神经胶质瘤的辅助化疗，但固有耐药性和获得性耐药性限制了顺铂的应用。据报道，长非编码RNA（lncRNA）DANCR可调节多种癌症的分化和进程。但是，DANCR是否参与神经胶质瘤的顺铂耐药性仍是未知的。在这项研究中，我们发现DANCR表达与神经胶质瘤细胞中的顺铂敏感性呈负相关。功能获得性和功能丧失性分析表明，DNACR在体外可减弱顺铂诱导的细胞增殖抑制，而在体内则可抑制异种移植的生长。此外，DNACR还减弱了顺铂诱导的细胞凋亡体外和体内。从机理上讲，我们发现DANCR通过竞争性结合miR-33a-5p，miR-33b-5p，miR-1-3p，miR-206和miR-613上调AXL。通过上调AXL，DANCR激活了胶质瘤细胞中的PI3K / Akt /NF-κB信号通路。抑制AXL / PI3K / Akt /NF-κB信号通路可逆转DANCR对顺铂耐药性的作用。总之，我们确定了顺铂耐药相关的lncRNA DANCR。DANCR通过激活神经胶质瘤中的AXL / PI3K / Akt /NF-κB信号通路来提高顺铂耐药性。我们的数据表明，DANCR可能是预测顺铂敏感性的潜在生物标志物，并且是增强神经胶质瘤顺铂功效的治疗靶标。