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The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells

Melania E Mercado-Pimentel1, Benjamin C Onyeagucha2, Qing Li3

  • 1Department of Pathology, University of Arizona, Tucson, AZ 85724, USA; University of Arizona Cancer Center, Tucson, AZ, USA.

FEBS Letters
|July 21, 2015
PubMed

Insights

S100P protein signaling activates microRNA-21 (miR-21) in colon cancer cells via the receptor for advanced glycation end-products (RAGE) and ERK pathways, promoting cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • S100P protein and its receptor for advanced glycation end-products (RAGE) pathway are implicated in colon cancer invasion and metastasis.
  • The precise molecular mechanisms linking S100P/RAGE signaling to colon cancer progression remain largely unknown.

Purpose of the Study:

  • To investigate the role of S100P/RAGE signaling in regulating the expression of the oncogenic microRNA-21 (miR-21) in human colon cancer cells.
  • To elucidate the signaling pathways involved in S100P-mediated miR-21 upregulation.

Main Methods:

  • Utilized human colon cancer cell lines.
  • Assessed miR-21 levels following S100P stimulation and knockdown.
  • Investigated the effect of RAGE blockade using an anti-RAGE antibody.
  • Examined the involvement of the ERK/MAPK pathway using the MEK inhibitor U0126.
  • Analyzed transcription factor binding at the miR-21 gene promoter using chromatin immunoprecipitation.

Main Results:

  • Exogenous S100P administration increased miR-21 levels in colon cancer cells.
  • Knockdown of S100P led to decreased miR-21 expression.
  • Blocking RAGE with an antibody inhibited S100P-induced miR-21 upregulation.
  • S100P-mediated miR-21 induction was dependent on the ERK signaling pathway.
  • S100P treatment enhanced the binding of c-Fos and AP-1 transcription factors to the miR-21 gene promoter.

Conclusions:

  • S100P signaling, through RAGE and the ERK pathway, upregulates oncogenic miR-21 in colon cancer.
  • This S100P/RAGE/ERK/miR-21 axis represents a novel mechanism contributing to colon cancer progression.
  • Targeting this pathway may offer therapeutic strategies for colon cancer treatment.
Keywords:
AP-1Colon cancerInflammationMetastasisRAGERECKTCGAmiR-21microRNAs

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