Role of SNHG7-miR-653-5p-STAT2 feedback loop in regulating neuroblastoma progression

J Cell Physiol. 2019 Aug;234(8):13403-13412. doi: 10.1002/jcp.28017. Epub 2019 Jan 8.

Abstract

Long noncoding RNAs (lncRNAs) are reported to be involved in the pathology of numerous cancers, including neuroblastoma (NB). lncRNA SNHG7 has been recognized as a carcinogen in several cancers, but its role in NB progression remains unknown. Our study revealed that SNHG7 expression was markedly higher in NB tissues than that in nontumor tissues. Besides, upregulated SNHG7 was greatly correlated with poor overall survival of NB patients. Functionally, the loss-of-function assays demonstrated that knockdown of SNHG7 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition in NB cells. Mechanically, the bioinformatics analysis predicted that miR-653-5p was the shared partner of SNHG7 and signal transducer and activator of transcription 2 (STAT2). Unsurprisingly, we further confirmed that SNHG7 could interact with miR-653-5p and therefore functioned as the ceRNA of STAT2 so as to regulate STAT2 expression in NB cells. Moreover, STAT2 expression was in inverse proportion to miR-653-5p level but in positive proportion to SNHG7 level in NB tissues. Importantly, the repressed NB progression induced by silenced SNHG7 was reversed by STAT2 overexpression or miR-653-5p inhibitors. Jointly, our findings elucidated SNHG7 facilitated NB progression through the miR-653-5p/STAT2 pathway, providing a novel therapeutic target and prognostic biomarker for this disease.

Keywords: lncRNA SNHG7; miR-653-5p; neuroblastoma (NB); proliferation; signal transducer and activator of transcription 2 (STAT2).

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Child, Preschool
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Feedback, Physiological
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Infant
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics
  • Neuroblastoma / genetics*
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • STAT2 Transcription Factor / metabolism*
  • Up-Regulation

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • STAT2 Transcription Factor
  • STAT2 protein, human