UPF1 regulates the malignant biological behaviors of glioblastoma cells via enhancing the stability of Linc-00313

There is growing evidence that the long non-coding RNAs(lncRNAs) play an important role in the biological behaviors of glioblastoma cells. In this study, we elucidated the function and possible effect and molecular mechanisms of lncRNA-Linc-00313 on the biological behaviors of glioblastoma cells as well as UPF1 function as a RNA-binding protein to enhance its stability. Here, we used qRT-PCR and western blot to measure the expression, cell Transfection to disrupt the expression of genes, cell viability analysis, quantization of apoptosis, cell migration, and invasion assays, Reporter vectors construction and luciferase assays to investigate the malignant biological behaviors of cells, human lncRNA microarrays, RNA-Immunoprecipitation, dual-luciferase gene reporter assay, half-life assay and chromatin immunoprecipitation to verify the binding sites, tumor xenograft implantation for in vivo experiment, SPSS 18.0 statistical software for data statistics. UPF1 and Linc-00313 were both upregulated in glioma tissues and cells. Knockdown of UPF1 or Linc-00313 significantly inhibited malignant biological behaviors of glioma cells by regulating miR-342-3p and miR-485-5p, which are downregulated and functioned as tumor suppressors in glioma. Furthermore, Linc-00313 could acted as a competing endogenous RNA(ceRNA) to regulate the expression of Zic4 by binding to miR-342-3p and miR-485-5p. Interestingly, Zic4 could bind to the promoters of UPF1 and Linc-00313 respectively and upregulate the expression of them. These results indicated that a positive-feedback loop was formed in the regulation of the biological behaviors of glioma cells. The study is the first to prove that the UPF1-Linc-00313-miR-342-3p/miR-485-5p-Zic4-SHCBP1 pathway forms a positive-feedback loop and regulates the biological behaviors of U87 and U251 cells, which might provide a new therapeutic target for glioma.