Long noncoding RNA nuclear enriched abundant transcript 1 impacts cell proliferation, invasion, and migration of glioma through regulating miR-139-5p/ CDK6

J Cell Physiol. 2019 May;234(5):5972-5987. doi: 10.1002/jcp.27093. Epub 2018 Dec 4.

Abstract

Aims: We aimed to explore the impact of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) on cell proliferation, invasion, and migration of glioma.

Methods: Differentially expressed genes were screened out from Gene Expression Omnibus data set based on the microarray analysis. The expression levels of lncRNA NEAT1, miR-139-5p, and CDK6 in glioma cells and tissues were examined by quantitative reverse transcription polymerase chain reaction, and the protein level of CDK6 in glioma cells was determined by western blot and immunohistochemistry. Glioma cell viability, cell cycle, and apoptosis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and flow cytometry, respectively, whereas cell invasion and migration were analyzed by transwell assay. The target relationships among NEAT1, miR-139-5p, and CDK6 were confirmed by dual-luciferase reporter gene assay. The effects of lncRNA NEAT1 on tumor growth were further testified through glioma xenografts in nude mice.

Results: LncRNA NEAT1 and CDK6 were highly expressed in glioma tissues and cells, whereas miR-139-5p was lowly expressed. There were target relationships and correlations on expressions between miR-139-5p and NEAT1/ CDK6. NEAT1 and CDK6 could promote cell proliferation and metastasis of glioma cells and impeded cell apoptosis, whereas miR-139-5p exerted suppressive effects on the biological functions of glioma cells. NEAT1 regulated CDK6 to affect glioma growth through sponging miR-139-5p.

Conclusions: LncRNA NEAT1 promotes cell proliferation, invasion, and migration of glioma through regulating miR-139-5p/CDK6 pathway.

Keywords: CDK6; glioma; invasion; long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1); miR-139-5p; migration; nude mouse model; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclin-Dependent Kinase 6 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glioma / enzymology*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Tumor Burden

Substances

  • MIRN139 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6