Department of Neurosurgery, The Second People Hospital of Xin Xiang, Xin Xiang, China.
Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Neoplasma. 2018 Sep 19;65(5):790-798. doi: 10.4149/neo_2018_170724N498. Epub 2018 Jun 17.
Glioma is among the most fatal brain tumors characterized by a highly malignancy and rapid progression and early metastasis. Dysregulation of long non-coding RNA differentiation antagonizing non-protein coding RNA (LncRNA DANCR) is associated with the development, progression and metastasis of various cancers. In the present study, we investigated functional role of LncRNA DANCR in the malignancy of glioma. The results showed that LncRNA DANCR was increased in glioma tissues and cells compared with normal brain tissues and cells. DANCR expression was positively correlated with the malignancy and poor prognosis of glioma patients. DANCR contained a binding site of miR-33a-5p. miR-33a-5p was decreased in glioma tissues and cells compared with normal brain tissues and cells. Downregulation of miR-33a-5p was positively correlated with the malignancy and poor prognosis of glioma patients. In glioma tissues, the expression of DANCR was negatively correlated with the expression of miR-33a-5p. Downregulation of DANCR increased miR-33a-5p expression. miR-33a-5p mimic reduced the luciferase of DANCR-WT but not DANCR-MUT. DANCR pull-down showed the expression of miR-33a-5p. miR-33a-5p mimic enhanced knockdown of DANCR -induced inhibition of cell proliferation, migration, and EMT, and increase of apoptosis. Anti-miR-33a-5p reversed the effects of si- DANCR on cell malignancy. Knockdown of DANCR remarkably reduced the increase of tumor volumes in xenograft mouse models. In tumor tissues, knockdown of DANCR increased the expression of miR-33a-5p, reduced EMT and increased apoptosis. Our study provides novel insights in the functions of LncRNA DANCR-miR-33a-5p axis in tumorigenesis of glioma.
神经胶质瘤是最致命的脑肿瘤之一，其特征为高度恶性、快速进展和早期转移。长链非编码 RNA 分化拮抗非蛋白编码 RNA（LncRNA DANCR）的失调与各种癌症的发生、发展和转移有关。在本研究中，我们研究了 LncRNA DANCR 在神经胶质瘤恶性中的功能作用。结果表明，与正常脑组织和细胞相比，神经胶质瘤组织和细胞中 LncRNA DANCR 增加。DANCR 表达与神经胶质瘤患者的恶性程度和预后不良呈正相关。DANCR 含有 miR-33a-5p 的结合位点。与正常脑组织和细胞相比，神经胶质瘤组织和细胞中 miR-33a-5p 减少。miR-33a-5p 的下调与神经胶质瘤患者的恶性程度和预后不良呈正相关。在神经胶质瘤组织中，DANCR 的表达与 miR-33a-5p 的表达呈负相关。下调 DANCR 增加了 miR-33a-5p 的表达。miR-33a-5p 模拟物降低了 DANCR-WT 的荧光素酶活性，但不降低 DANCR-MUT 的荧光素酶活性。DANCR 下拉显示 miR-33a-5p 的表达。miR-33a-5p 模拟物增强了 DANCR 敲低诱导的细胞增殖、迁移和 EMT 抑制以及细胞凋亡增加。抗 miR-33a-5p 逆转了 si-DANCR 对细胞恶性的影响。DANCR 敲低显著减少了异种移植小鼠模型中肿瘤体积的增加。在肿瘤组织中，DANCR 敲低增加了 miR-33a-5p 的表达，减少了 EMT 并增加了凋亡。我们的研究为 LncRNA DANCR-miR-33a-5p 轴在神经胶质瘤发生中的作用提供了新的见解。
