UPF1 alleviates the progression of glioma via targeting lncRNA CYTOR

Eur Rev Med Pharmacol Sci. 2019 Nov;23(22):10005-10012. doi: 10.26355/eurrev_201911_19567.

Abstract

Objective: To uncover the role of UPF1 in alleviating the progression of glioma via targeting long non-coding RNA (lncRNA) CYTOR and underlying mechanism.

Patients and methods: A total of 30 glioma tissues surgically resected from glioma patients and 30 brain tissues were collected from brain trauma patients undergoing craniotomy during the same period. Relative levels of UPF1 and CYTOR in collected tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between levels of UPF1 and CYTOR in glioma tissues was assessed, and the regulatory effects of UPF1/CYTOR on proliferative and invasive abilities in U87 and LN229 cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assay, respectively. In addition, the interaction between UPF1 and CYTOR was explored by RIP (RNA-Binding Protein Immunoprecipitation) assay. Through Actinomycin D treatment in U87 and LN229 cells, RNA stability of CYTOR influenced by UPF1 was determined. Finally, rescue experiments were conducted to ascertain the involvement of CYTOR in UPF1-regulated progression of glioma.

Results: UPF1 was downregulated in glioma tissues and cells. A lower level of UPF1 was observed in glioma tissues in the more advanced stage with a larger tumor size. Besides, the overexpression of UPF1 markedly suppressed proliferation and invasion abilities of U87 and LN229 cells, and CYTOR was upregulated in glioma tissues and cells, which was negatively correlated with UPF1 level. Moreover, the overexpression of UPF1 decreased the half-life of CYTOR in glioma cells. Furthermore, the RIP assay confirmed the interaction between UPF1 and CYTOR. Rescue experiments finally confirmed that the overexpression of CYTOR partially reversed the inhibitory effects of UPF1 on proliferation and invasion abilities in glioma.

Conclusions: UPF1 is down-regulated in glioma and alleviates the progression of glioma via targeting CYTOR.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Glioma
  • Humans
  • Neoplasm Staging
  • RNA Helicases / genetics*
  • RNA Helicases / metabolism*
  • RNA, Long Noncoding / genetics*
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism*
  • Tumor Burden

Substances

  • RNA, Long Noncoding
  • Trans-Activators
  • long non-coding RNA Linc00152, human
  • RNA Helicases
  • UPF1 protein, human