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.

Glioma is a serious malignant tumor without effective therapies till now. lncRNA PEG10 was reported to have some biological activities in cancers. Hence, we explored the effects of PEG10 on the human glioma cell line U251 cells. U251 cells were transfected with sh-PEG10 and/or miR-506 inhibitor. The expression of PEG10 and miR-506 was measured by qRT-PCR. Cell viability, cell apoptosis, cell migration and invasion were detected by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. The cell proliferation and apoptosis related p16, p53, Bcl-2, Bax, and pro-/Cleaved-Caspase-3/9, migration and invasion related-protein: matrix metalloproteinases MMP-2, MMP-9 and vimentin, and Raf/MEK/ERK and JAK1/STAT3 pathways-related proteins were accessed by Western blot. Transfection with sh-PEG10 inhibited cell viability, migration and invasion, and increased cell apoptosis. Meanwhile, PEG10 silence upregulated the expression of p16 and p53, Bax, cleaved-Caspase-3/9 expression, and downregulated Bcl-2 expression. PEG10 silence upregulated miR-506 expression. Co-transfection with sh-PEG10 and miR-506 inhibitor impaired the tumor suppressive effects. PEG10 knockdown decreased the phosphorylation of Raf/MEK/ERK and JAK1/STAT3-related proteins Raf, MEK, ERK, JAK1 and STAT3. PEG10 knockdown inhibited cell viability, migration and invasion, induced cell apoptosis through miR-506 upregulation, as well as inactivation of Raf/MEK/ERK and JAK1/STAT3 signal pathways.

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