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Implication of TrkC-miR2 in neurotrophin signalling pathway regulation through NGFR transcript targeting

Sadat Dokaneheifard1,2, Bahram M Soltani1

  • 1Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Journal of Cellular and Molecular Medicine
|March 6, 2021
PubMed

Insights

TrkC-miR2 regulates neurotrophin signaling by targeting NGFR, impacting cell survival and differentiation. This microRNA plays a key role in neural development and may influence cancer pathways.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Cell Biology

Background:

  • TrkC and NGFR neurotrophin receptors are implicated in cell death, cancer, and differentiation.
  • TrkC-miR2, within the TrkC gene, regulates the Wnt signaling pathway, with broader pathway influence under investigation.

Purpose of the Study:

  • To investigate the regulatory role of TrkC-miR2 in neurotrophin signaling pathways.
  • To identify the direct targets of TrkC-miR2 and its functional consequences on cell behavior and differentiation.

Main Methods:

  • RT-qPCR and dual-luciferase assays to confirm TrkC-miR2 targeting of NGFR.
  • Western blotting to assess the expression of key proteins in neurotrophin signaling.
  • Flow cytometry and MTT assays to evaluate cell survival rates.
  • Analysis of TrkC-miR2 and NGFR/TrkC expression during NT2 cell differentiation.

Main Results:

  • TrkC-miR2 was experimentally validated as a direct target of NGFR.
  • Overexpression of TrkC-miR2 modulated the expression of TrkA, TrkC, NFKB, BCL2, and Akt2.
  • TrkC-miR2 overexpression increased survival rates in HEK293t and U87 cells.
  • An inverse correlation between TrkC-miR2 and NGFR/TrkC expression was observed during NT2 differentiation, with TrkC-miR2 downregulation impairing neural differentiation.

Conclusions:

  • TrkC-miR2 acts as a novel regulator of the neurotrophin signaling pathway.
  • TrkC-miR2 influences cell survival and differentiation, suggesting its involvement in neural development and potentially cancer.
  • The findings provide in silico and experimental evidence for TrkC-miR2's role in controlling neurotrophin signaling.
Keywords:
NGFRTrkC-miR2neurotrophin signalling pathway

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