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Ribosomal S6 kinase 4 (RSK4) tumor suppressor gene promoter methylation status in ovarian cancer

Fabian Arechavaleta-Velasco1, Pablo Dominguez-Lopez1, Ernesto Acosta-Jimenez1,2

  • 1Unidad de Investigación Médica en Medicina Reproductiva, UMAE Hospital de Gineco-Obstetricia No. 4 "Luis Castelazo Ayala", Instituto Mexicano del Seguro Social, Av. Rio Magdalena No. 289, Sexto piso. Tizapán, San Angel, CP 01090, Mexico City, Mexico.

Molecular Biology Reports
|July 4, 2023
PubMed
Abstract

Insights

Ovarian tumors show increased RSK4 promoter methylation, but it doesn't fully explain low RSK4 expression. Reactivating RSK4 expression reduced proliferation in specific ovarian cancer subtypes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Reduced RSK4 mRNA and protein levels are observed in malignant ovarian tumors.
  • A significant inverse correlation exists between advanced ovarian cancer stages and RSK4 mRNA levels.
  • The mechanisms driving RSK4 downregulation in ovarian cancer remain unclear.

Purpose of the Study:

  • To investigate if RSK4 promoter methylation causes reduced RSK4 expression in ovarian cancer.
  • To explore RSK4 expression reactivation and its effects in ovarian cancer cell lines.

Main Methods:

  • Combined bisulfite restriction analysis to assess RSK4 promoter methylation.
  • Decitabine treatment to induce RSK4 reactivation in ovarian cancer cell lines (OVCAR3, SKOV3, TOV-112D, TOV-21G).
  • Western blotting for RSK4 expression, and XTT assay for cell proliferation.

Main Results:

  • Significantly higher RSK4 promoter methylation was found in malignant and benign ovarian tumors compared to normal tissue.
  • RSK4 promoter methylation did not correlate with age, histological subtype, or cancer stage.
  • Decitabine treatment reactivated RSK4 expression in all tested cell lines, but reduced proliferation only in TOV-112D cells.

Conclusions:

  • RSK4 promoter methylation is increased in ovarian tumors but is unlikely the primary regulator of RSK4 expression in ovarian cancer.
  • RSK4 reactivation demonstrated a selective inhibitory effect on cell proliferation, particularly in the endometrioid histological subtype.
Keywords:
MethylationOvarian cancerRibosomal S6 kinase 4 (RSK4)

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