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miR-205 Inhibits Neuroblastoma Growth by Targeting cAMP-Responsive Element-Binding Protein 1

Shu Chen1, Lianhua Jin2, Shu Nie2

  • 1Department of Thoracic Surgery, The Second Hospital of Jilin UniversityChangchunP.R. China.

Oncology Research
|June 28, 2017
PubMed

Insights

MicroRNA-205 (miR-205) acts as a tumor suppressor in neuroblastoma (NB). Restoring miR-205 inhibits NB cell growth and metastasis by targeting cAMP-responsive element-binding protein 1 (CREB1).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-205 (miR-205) is implicated in various cancers, but its role in neuroblastoma (NB) is not well understood.
  • Neuroblastoma is a pediatric cancer with significant unmet needs in understanding its molecular drivers.

Purpose of the Study:

  • To investigate the function of miR-205 in neuroblastoma.
  • To identify the molecular targets of miR-205 in NB.

Main Methods:

  • Quantitative real-time PCR to measure miR-205 and CREB1 expression in NB tissues and cell lines.
  • In vitro assays (proliferation, migration, invasion, apoptosis) and in vivo tumor xenograft models to assess miR-205 function.
  • Western blotting and luciferase reporter assays to validate CREB1 as a direct target of miR-205.

Main Results:

  • miR-205 was significantly downregulated in NB tissues and cell lines, correlating with advanced stage and poor differentiation.
  • Restoration of miR-205 suppressed NB cell proliferation, migration, invasion, and tumor growth, while inducing apoptosis.
  • cAMP-responsive element-binding protein 1 (CREB1) was identified as a direct target of miR-205; CREB1 was upregulated in NB and inversely correlated with miR-205 levels. Upregulation of CREB1 partially rescued the tumor-suppressive effects of miR-205.

Conclusions:

  • miR-205 functions as a tumor suppressor in neuroblastoma.
  • The tumor-suppressive role of miR-205 in NB is mediated, at least in part, through the inhibition of its direct target, CREB1.

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