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Neurochem Int. 2018 Sep;118:233-241. doi: 10.1016/j.neuint.2018.03.011. Epub 2018 Mar 21.

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

Author information

1
Department of Neurosurgery, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, 252000, China.
2
Department of Neurosurgery, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, 252000, China. Electronic address: kai_linvvv@163.com.

Abstract

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.

KEYWORDS:

Chemoresistance; Cisplatin; Glioma; Long noncoding RNA; PI3K/Akt/NF-κB signaling pathway

PMID:
29572052
DOI:
10.1016/j.neuint.2018.03.011
[Indexed for MEDLINE]

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