Long noncoding RNA nuclear-enriched abundant transcript 1 regulates proliferation and apoptosis of neuroblastoma cells treated by cisplatin by targeting miR-326 through Janus kinase/signal transducer and activator of transcription 3 pathway

Neuroreport. 2020 Dec 9;31(17):1189-1198. doi: 10.1097/WNR.0000000000001538.

Abstract

Neuroblastoma is a common malignancy and frequently affects children, leading to a low survival rate. Long noncoding RNAs (lncRNAs) are reported to be closely related to cancer progression. The purpose of this study was to explore a novel mechanism of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in neuroblastoma. NEAT1 was upregulated in neuroblastoma cell lines (IMR32 and SK-N-SH). Overexpression of NEAT1 increased proliferation inhibited by cisplatin and decreased apoptosis promoted by cisplatin. MicroRNA-326 (miR-326) was a target of NEAT1 and miR-326 reintroduction abolished the effects of NEAT1 overexpression on cell proliferation and apoptosis. Moreover, NEAT1 overexpression activated Janus kinase/signal transducer and activator of transcription 3 (JAK1/STAT3) signaling pathway through absorbing miR-326. Besides, NEAT1 overexpression promoted tumor growth in vivo through stimulating the expression of p-JAK1 and p-STAT3 but inhibiting miR-326 expression. NEAT1 accelerated proliferation and weakened apoptosis of neuroblastoma cells treated by cisplatin by targeting miR-326 through activating JAK1/STAT3 signaling pathway, suggesting that NEAT1 was a potential biomarker against neuroblastoma.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Cisplatin / administration & dosage*
  • Drug Delivery Systems / methods
  • Female
  • Humans
  • Janus Kinase 1 / biosynthesis*
  • Janus Kinase 1 / genetics
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • STAT3 Transcription Factor / biosynthesis*
  • STAT3 Transcription Factor / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • MIRN326 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • JAK1 protein, human
  • Janus Kinase 1
  • Cisplatin