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Epigenetic Downregulation of Hsa-miR-193b-3p Increases Cyclin D1 Expression Level and Cell Proliferation in Human

Paulina Kober1, Beata Joanna Mossakowska1, Natalia Rusetska2

  • 1Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.

International Journal of Molecular Sciences
|September 9, 2023
PubMed

Insights

DNA hypermethylation of the MIR193B gene causes downregulation of hsa-miR-193b-3p in meningiomas. This microRNA acts as a tumor suppressor by inhibiting cyclin D1, thus reducing cell proliferation.

Area of Science:

  • Neuro-oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Meningiomas are common adult intracranial tumors with pathogenesis influenced by abnormal microRNA (miRNA) expression.
  • Epigenetic dysregulation, specifically DNA methylation, can alter miRNA levels in tumors.
  • The role of MIR193B and its encoded miRNAs in meningioma development requires further elucidation.

Purpose of the Study:

  • To investigate the epigenetic regulation of MIR193B in meningiomas.
  • To determine the expression levels of hsa-miR-193b in relation to meningioma grade.
  • To identify the functional role of hsa-miR-193b in meningioma cell proliferation.

Main Methods:

  • Genome-wide methylation analysis using HumanMethylation450K Illumina arrays.
  • Bisulfite pyrosequencing for targeted MIR193B methylation analysis.
  • Quantitative real-time PCR for miRNA and mRNA expression analysis.
  • Luciferase reporter assay and cell viability assays in meningioma cell lines.

Main Results:

  • The genomic region of MIR193B was found to be hypermethylated in meningiomas.
  • Both hsa-miR-193b-3p and hsa-miR-193b-5p were downregulated in meningiomas, with lower hsa-miR-193b-3p expression and higher MIR193B methylation in higher-grade tumors (WHO GII/III).
  • hsa-miR-193b-3p directly targets CCND1 mRNA, and its overexpression suppressed meningioma cell viability and proliferation.

Conclusions:

  • MIR193B hypermethylation contributes to hsa-miR-193b-3p downregulation in meningiomas.
  • hsa-miR-193b-3p acts as a tumor suppressor by negatively regulating cyclin D1 expression and cell proliferation.
  • hsa-miR-193b-3p represents a potential therapeutic target for meningioma treatment.
Keywords:
DNA methylationcyclin D1epigeneticshsa-miR-193b-3pmeningiomamicroRNA

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