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S-Adenosylmethionine Inhibits Colorectal Cancer Cell Migration through Mirna-Mediated Targeting of Notch Signaling

Luigi Borzacchiello1, Roberta Veglia Tranchese1, Roberta Grillo1

  • 1Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 7, 80138 Naples, Italy.

International Journal of Molecular Sciences
|July 27, 2022
PubMed

Insights

S-adenosyl-L-methionine (AdoMet) combats colorectal cancer (CRC) metastasis by upregulating tumor-suppressing microRNAs (miRNAs) that target the Notch pathway, inhibiting cancer cell migration and EMT markers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Colorectal cancer (CRC) metastasis is a primary cause of mortality.
  • Dysregulated Notch signaling is implicated in CRC progression and metastasis.
  • MicroRNAs (miRNAs) regulate Notch, offering a potential therapeutic target.

Purpose of the Study:

  • To investigate S-adenosyl-L-methionine (AdoMet) as a potential antimetastatic agent in CRC.
  • To explore the role of AdoMet in modulating miRNA expression and Notch signaling.
  • To determine if AdoMet's antimetastatic effects are mediated by miRNA-dependent Notch inhibition.

Main Methods:

  • Cell culture of CRC cell lines (HCT-116, Caco-2).
  • AdoMet treatment to assess effects on miRNA and protein expression.
  • Luciferase assays to confirm direct miRNA targeting of Notch.
  • Gain- and loss-of-function experiments using miRNA mimics and inhibitors.

Main Results:

  • AdoMet upregulated tumor-suppressor miRNAs (miRNAs-34a/-34c/-449a) in CRC cells.
  • AdoMet inhibited migration and reduced expression of migration/EMT markers.
  • AdoMet directly targeted the Notch gene via miRNAs-34a/-34c/-449a.
  • AdoMet's inhibitory effects were dependent on the upregulation of these miRNAs.

Conclusions:

  • AdoMet acts as a novel inhibitor of Notch signaling in CRC.
  • The antimetastatic effects of AdoMet are mediated through miRNA-dependent suppression of the Notch pathway.
  • Targeting the miRNA-Notch axis with AdoMet presents a promising therapeutic strategy for CRC metastasis.
Keywords:
EMTNotchS-Adenosylmethioninebreast cancercolorectal cancermetastasismiRNA

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