LncRNA NEAT1 Enhances Glioma Progression via Regulating the miR-128-3p/ITGA5 Axis

Mol Neurobiol. 2021 Oct;58(10):5163-5177. doi: 10.1007/s12035-021-02474-y. Epub 2021 Jul 15.

Abstract

Accumulating evidences indicate that long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) promotes the progression of glioma. In this study, we postulated that NEAT1 may act as a miR-128-3p sponge. Relative levels of NEAT1 and miR-128-3p expression in human glioma samples and GBM cells were detected using quantitative real-time PCR. By means of CCK-8 assays, transwell assays, and flow cytometric analysis, the biological functions of miR-128-3p and NEAT1 were investigated in U87MG and U251MG human GBM cell lines with stable miR-128-3p and NEAT1 knockdown or overexpression. The luciferase reports, RNA pull-down assay, and RNA immunoprecipitation assay were conducted to determine the relevance of NEAT1 and miR-128-3p in glioma. As a result, high expression of NEAT1 and lack of miR-128-3p were observed in glioma specimens and cells. By binding to anti-oncogene miR-128-3p in the nucleus, NEAT1 enhanced tumorigenesis and glioma development. Further experiments suggested that ITGA5 expression was increased in glioma tissues and was found to be connected with miR-128-3p. Additionally, NEAT1 facilitated ITGA5 expression via competitively binding to miR-128-3p. For this reason, ITGA5 would not be decomposed by miR-128-3p and could activate FAK signaling pathway, thereby promoting cell growth. Collectively, these results indicated that the NEAT1/miR-128-3p/ITGA5 axis was involved in glioma initiation and progression, and might offer a potential novel strategy for treatment of glioma.

Keywords: FAK; Glioma; ITGA5; NEAT1; miR-128-3p.

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Disease Progression*
  • Glioma / genetics
  • Glioma / metabolism*
  • Humans
  • Integrins / genetics
  • Integrins / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Xenograft Model Antitumor Assays / methods

Substances

  • ITGA5 protein, human
  • Integrins
  • MIRN128 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding