Cleft Palate Induced by Mycophenolate Mofetil Is Associated with miR-4680-3p and let-7c-5p in Human Palate Cells

Hiroki Yoshioka1,2, Hanane Horita1, Yosuke Tsukiboshi1

  • 1Faculty of Pharmacy, Gifu University of Medical Science, 4-3-3 Nijigaoka, Kani, Gifu 509-0293, Japan.

Non-Coding RNA
|February 25, 2025
PubMed

Insights

Mycophenolate mofetil (MPM) exposure during pregnancy can cause cleft palate by disrupting cell proliferation in human embryonic palatal mesenchymal cells. This disruption is linked to increased miR-4680-3p and let-7c-5p microRNA levels.

Area of Science:

  • Developmental biology
  • Molecular biology
  • Genetics

Background:

  • Cleft palate is a birth defect influenced by genetic and environmental factors.
  • Medications during pregnancy, like mycophenolate mofetil (MPM), and microRNA (miRNA) dysregulation are implicated in cleft palate development.
  • The precise molecular link between MPM exposure and miRNA changes in cleft palate remains unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms of MPM-induced inhibition of cell proliferation and miRNA expression in human embryonic palatal mesenchymal (HEPM) cells.
  • To identify specific miRNAs involved in MPM-induced cleft palate.

Main Methods:

  • HEPM cells were treated with MPM, and cell viability, apoptosis, and cell cycle markers were assessed.
  • miRNA expression levels and their downstream gene targets were quantified.
  • Rescue experiments were conducted using inhibitors for miR-4680-3p and let-7c-5p.

Main Results:

  • MPM reduced HEPM cell viability in a dose-dependent manner.
  • MPM suppressed the expression of cell cycle regulators (cyclin-D1, cyclin E1, CDK-2, CDK6).
  • MPM upregulated miR-4680-3p and let-7c-5p, subsequently downregulating their target genes.
  • Inhibiting miR-4680-3p and/or let-7c-5p partially reversed MPM's effects on cell proliferation.

Conclusions:

  • MPM-induced cleft palate in HEPM cells is associated with the upregulation of miR-4680-3p and let-7c-5p.
  • These miRNAs play a role in mediating the inhibitory effects of MPM on palatal cell proliferation.

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