Long noncoding RNA DANCR knockdown inhibits proliferation, migration and invasion of glioma by regulating miR-135a-5p/BMI1

Abstract

BackgroundGlioma 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.MethodsThe 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.ResultsDANCR 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.ConclusionDANCR 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.