CpG Methylation of Protein Prenyltransferase Genes FNTA, FNTB, PGGT1B and RABGGTA in Cancer Cell Lines

TL;DR

This study investigates how DNA methylation affects the expression of prenyltransferase genes in cancer and benign cells.

Contribution

The study is the first to explore DNA methylation as a potential cause of aberrant prenyltransferase expression in cancer.

Findings

Methylation levels of PTase genes were similar in benign and cancer cells overall.

PGGT1B methylation inversely correlated with mRNA expression in cancer cells.

Caki-1 cells showed significant methylation differences in PGGT1B, suggesting a role in dysregulation.

Abstract

Background: Protein prenylation is crucial for the function of hundreds of proteins. Aberrant protein prenylation can be caused by the aberrant expression of prenyltransferases (PTases), which has been reported for multiple cancer entities. The reasons for aberrant PTase expression in cancer have not yet been investigated. Methods: We analyzed CpG methylation within promoter-associated CpG islands of the PTase genes FNTA, FNTB, PGGT1B, and RABGGTA via bisulfite conversion and pyrosequencing to assess its role in PTase expression and gain deeper insight into the regulation of protein prenylation in cancer. We used DNA from three benign controls (whole blood samples, peripheral blood mononuclear cells, and HEK293) and 19 human cancer cell lines from various origins to assess DNA methylation within PTase gene promoter-associated CpG islands. For a subset of these cell lines, we measured mRNA expression via qPCR and correlated it with DNA methylation. Results: Methylation across all PTase genes ranged from 1.9 ± 0.9% to 11.4 ± 4.0% (mean methylation ± standard deviation) in benign cells, and 2.3 ± 1.0% to 16.0 ± 5.4% in cancer cells. DNA methylation and mRNA expression of PGGT1B correlated inversely (PCC = −0.75; p = 0.005). Conclusions: We saw no general differences between benign and malignant cells, but observed significant differences between non-malignant controls and multiple individual cancer cell lines regarding the methylation of PTase genes. This was prominently seen in PGGT1B in Caki-1 cells, raising the possibility that DNA methylation is involved in the dysregulation of PTase expression in cancer.

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