Long noncoding RNA DANCR mediates cisplatin resistance in glioma cells via activating AXL/PI3K/Akt/NF-κB signaling pathway

• Published in: Neurochemistry international Vol. 118; pp. 233 - 241
• Main Authors: Ma, Yangang, Zhou, Guanghua, Li, Mengyou, Hu, Dianfeng, Zhang, Lianqun, Liu, Peng, Lin, Kai
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2018
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Cell Line, Tumor; Chemoresistance; Cisplatin; Cisplatin - pharmacology; Cisplatin - therapeutic use; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm - physiology; Female; Glioma; Glioma - drug therapy; Glioma - metabolism; Humans; Long noncoding RNA; Mice; Mice, Inbred BALB C; Mice, Nude; NF-kappa B - metabolism; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt/NF-κB signaling pathway; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-akt - metabolism; Receptor Protein-Tyrosine Kinases - biosynthesis; RNA, Long Noncoding - biosynthesis; RNA, Long Noncoding - genetics; Signal Transduction - drug effects; Signal Transduction - physiology; Xenograft Model Antitumor Assays; lncRNA; TUNEL; Glioma; PI3K/Akt/NF-κB signaling pathway; miRNAs; ceRNAs; Chemoresistance; qPCR; Long noncoding RNA; DANCR; Cisplatin
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2018.03.011

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. •DANCR expression was negatively correlated with cisplatin sensitivity in glioma cells.•DNACR attenuated cisplatin-induced cell proliferation inhibition and xenograft growth suppression.•DNACR attenuated cisplatin-induced cell apoptosis.•DANCR upregulated AXL via competitively binding common microRNAs.•DANCR activated PI3K/Akt/NF-κB signaling pathway.