SNHG1 promotes malignant biological behaviors of glioma cells via microRNA-154-5p/miR-376b-3p- FOXP2- KDM5B participating positive feedback loop

J Exp Clin Cancer Res. 2019 Feb 6;38(1):59. doi: 10.1186/s13046-019-1063-9.


Background: Long non-coding RNAs has been reported in tumorigenesis and play important roles in regulating malignant behavior of cancers, including glioma.

Methods: According to the TCGA database, we identified SNHG1, miRNA-154-5p and miR-376b-3p whose expression were significantly changed in the glioma samples. Furthermore, we investigated SNHG1, miRNA-154-5p and miR-376b-3p expression in clinical samples and glioma cell lines using qRT-PCR analysis and the correlation between them using RNA immunoprecipitation and dual-luciferase reporter. The underlying mechanisms of SNHG1 in glioma were also investigated using immunohistochemistry staining, Western blotting, chromatin immunoprecipitation, and RNA pulldown. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate malignant biological behaviors.

Results: We have elucidated the potential molecular mechanism of long non-coding RNA SNHG1 regulating the malignant behavior of glioma cells by binding to microRNA-154-5p or miR-376b-3p. Moreover, our deep-going results showed that FOXP2 existed as a direct downstream target of both microRNA-154-5p and miR-376b-3p; FOXP2 increased promoter activities and enhanced the expression of the oncogenic gene KDM5B; and KDM5B also acts as a RNA-binding protein to maintain the stability of SNHG1.

Conclusion: Collectively, this study demonstrates that the SNHG1- microRNA-154-5p/miR-376b-3p- FOXP2- KDM5B feedback loop plays a pivotal role in regulating the malignant behavior of glioma cells.

Keywords: Glioma; Long non-coding RNA; Oncogenes; Transcription factor; microRNA.

MeSH terms

  • Animals
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Central Nervous System Neoplasms / metabolism
  • Feedback, Physiological*
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glioma / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / biosynthesis
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / metabolism*
  • Survival Analysis


  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • MIRN154 microRNA, human
  • MIRN376C microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • Repressor Proteins
  • long non-coding RNA SNHG1, human
  • Jumonji Domain-Containing Histone Demethylases
  • KDM5B protein, human
  • Proto-Oncogene Proteins c-akt