Knockdown of lncRNA‐UCA1 inhibits cell viability and migration of human glioma cells by miR‐193a‐mediated downregulation of CDK6

BACKGROUND: Long noncoding RNA urothelial carcinoma-associated 1 (lncRNA-UCA1) is generally recognized as an oncogenic molecule in several human malignant tumors. However, the available evidence does not necessarily imply an unequivocal causal function of UCA1 in glioblastoma. The current study was aimed to probe the biological function of lncRNA-UCA1 in human glioblastoma cell lines. Besides, we further investigated the potential mechanisms. METHODS: Cell viability, apoptosis, as well as migration and invasion were measured using a commercial cell counting kit-8, flow cytometry, and 24-Transwell assay, respectively. LncRNA-UCA1, microRNA-193a (miR-193a), and CDK6 at messenger RNA levels were evaluated by quantitative real-time polymerase chain reaction method. Protein level was examined by Western blot analysis. RNA immunoprecipitation was utilized to validate lncRNA-UCA1 associated with miR-193a. Luciferase activity assay was used to identify the miR-193a-targeted CDK6 3'-untranslated region. RESULTS: lncRNA-UCA1 knockdown weakened cell viability, augmented apoptosis progression, as well as suppressed migration and invasion behaviors in glioblastoma cells, whereas lncRNA-UCA1 silence exhibited the opposite functions. lncRNA-UCA1 functioned as an endogenous sponge of miR-193a. miR-193a silence reversed the biological function of lncRNA-UCA1 knockdown on U-118 MG cells. miR-193a negatively regulated the expression of CDK6, and it affected the U-118 MG cells through regulating CDK6 expression. CDK6 overexpression abrogated the blockage of PI3K/AKT, mitogen-activated protein kinase (MAPK), and Notch signaling pathways. Furthermore, lncRNA-UCA1 and miR-193a could affect these signaling cascades through regulating CDK6 expression. The regulatory mechanisms of lncRNA-UCA1 were further consolidated in clinical specimens. CONCLUSION: lncRNA-UCA1 silence reduced cell viability, promoted apoptosis progression, while impeding the migration and invasion of glioblastoma cells by miR-193a-mediated silence of CDK6, with blockage of PI3K/AKT, MAPK, and Notch pathways.