Background Glioma is the most common and aggressive primary brain tumor with high mortality rate around the world. LncRNAs have been identified to play key roles in tumorigenesis in various cancers, including glioma. However, the precise mechanism of DANCR in progression of glioma remains poorly defined. Methods The expression levels of DANCR, miR-135a-5p and BMI1 were measured by qRT-PCR in glioma tissues and cells. Cell proliferation, migration and invasion were detected by CCK-8 assay and transwell assay, respectively. The possible binding sites of miR-135a-5p and DANCR or BMI1 were predicted by online software and verified using luciferase report assay and RNA immunoprecipitation (RIP) assay. Western blot analysis was carried out to detect the protein of BMI1 expression. A xenograft tumor model was established to investigate the functions of DANCR in glioma progression in vivo. Results DANCR was upregulated and miR-135a-5p was downregulated in glioma tissues and cells. Knockdown of DANCR inhibited cell proliferation, migration and invasion in glioma cells. In addition, miR-135a-5p was a direct target of DANCR, and its elevated expression could reverse miR-135a-5p inhibition-mediated progression of glioma. Moreover, miR-135a-5p could specially bind to BMI1, and the expression of BMI1 was obviously elevated in glioma tissues and cells. Furthermore, DANCR acted as a ceRNA to regulate BMI1 expression and BMI1-mediated effects on progression of glioma by sponging miR-135a-5p. Besides, inhibition of DANCR limited tumor growth by regulating miR-135a-5p and BMI1 expression in vivo. Conclusion DANCR knockdown inhibited cell proliferation, migration and invasion in glioma cells through regulating miR-135a-5p/BMI1 axis, providing viable therapeutic avenues for treatment of glioma.

中文翻译：

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长链非编码 RNA DANCR 敲低通过调节 miR-135a-5p/BMI1 抑制胶质瘤的增殖、迁移和侵袭。

背景 胶质瘤是世界上最常见、最具侵袭性的原发性脑肿瘤，死亡率很高。已确定 LncRNA 在包括神经胶质瘤在内的各种癌症的肿瘤发生中起关键作用。然而，DANCR 在胶质瘤进展中的确切机制仍不清楚。方法采用qRT-PCR方法检测胶质瘤组织和细胞中DANCR、miR-135a-5p和BMI1的表达水平。CCK-8法和transwell法分别检测细胞增殖、迁移和侵袭。通过在线软件预测miR-135a-5p和DANCR或BMI1的可能结合位点，并使用荧光素酶报告测定和RNA免疫沉淀（RIP）测定进行验证。进行蛋白质印迹分析以检测BMI1表达的蛋白质。建立异种移植肿瘤模型以研究 DANCR 在体内神经胶质瘤进展中的功能。结果DANCR在胶质瘤组织和细胞中上调，miR-135a-5p下调。敲除 DANCR 可抑制胶质瘤细胞的增殖、迁移和侵袭。此外，miR-135a-5p 是 DANCR 的直接靶点，其升高的表达可以逆转 miR-135a-5p 抑制介导的胶质瘤进展。此外，miR-135a-5p可以特异性结合BMI1，在胶质瘤组织和细胞中BMI1的表达明显升高。此外，DANCR 作为 ceRNA 通过海绵化 miR-135a-5p 调节 BMI1 表达和 BMI1 介导的对胶质瘤进展的影响。此外，抑制 DANCR 通过调节体内 miR-135a-5p 和 BMI1 表达来限制肿瘤生长。