CKAP2L Knockdown Exerts Antitumor Effects by Increasing miR-4496 in Glioblastoma Cell Lines

Abstract

Despite advances in the diagnosis and treatment of the central nervous system malignancy glioma, overall survival remains poor. Cytoskeleton-associated protein 2-like (<i>CKAP2L</i>), which plays key roles in neural progenitor cell division, has also been linked to poor prognosis in lung cancer. In the present study, we investigated the role of <i>CKAP2L</i> in glioma. From bioinformatics analyses of datasets from The Cancer Gene Atlas and the Chinese Glioma Genome Atlas, we found that <i>CKAP2L</i> expression correlates with tumor grade and overall survival. Gene set enrichment analysis (GSEA) showed that MITOTIC_SPINDLE, G2M_CHECKPOINT, and E2F_TARGETS are crucially enriched phenotypes associated with high <i>CKAP2L</i> expression. Using U87MG, U118MG, and LNZ308 human glioma cells, we confirmed that <i>CKAP2L</i> knockdown with si<i>CKAP2L</i> inhibits glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Interestingly, <i>CKAP2L</i> knockdown also induced cell cycle arrest at G2/M phase, which is consistent with the GSEA finding. Finally, we observed that <i>CKAP2L</i> knockdown led to significant increases in miR-4496. Treating cells with exogenous miR-4496 mimicked the effect of <i>CKAP2L</i> knockdown, and the effects of <i>CKAP2L</i> knockdown could be suppressed by miR-4496 inhibition. These findings suggest that <i>CKAP2L</i> is a vital regulator of miR-4496 activity and that <i>CKAP2L</i> is a potentially useful prognostic marker in glioma.