Promoter Methylation of the MGRN1 Gene Response to Chemotherapy of Epithelial Ovarian Cancer Patients

Objective: Aberrant DNA methylation is considered to play a critical role in the chemoresistance of epithelial ovarian cancer (EOC). In this study, we explored the relationship between hypermethylation of the Mahogunin Ring Finger 1 (MGRN1) gene promoter and primary chemoresistance in EOC patients.Methods: Hypermethylation of the MGRN1 promoter region in the cancer tissues of platinum-resistant EOC patients was observed by genome-wide methylation level analysis. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was used to analyze the methylation level of the MGRN1 promoter region. MGRN1 mRNA and protein expression were examined using RT-qPCR and IHC assays, respectively. The effect of MGRN1 methylation on the cellular response to cisplatin was detected by knockdown assays in SKOV3 cells. Additionally, we performed transcriptome analysis using RNA-seq and explored the possible mechanism by which MGRN1 expression affects the resistance of ovarian cancer cells to platinum. Results: The RRBS assay showed that the upstream region of MGRN1 from -1148 to -1064 was significantly hypermethylated in chemoresistant EOC patients (P=1.78×10−7). The MALDI-TOF mass spectrometry assays revealed a strong association between hypermethylation of the MGRN1 upstream region and platinum resistance in patients with EOC. Spearman’s correlation analysis revealed a significantly negative connection between the methylation level of MGRN1 and its expression in EOC. In vitro analysis demonstrated that knockdown of MGRN1 reduced the sensitivity of cells to cisplatin and that expression of EGR1 was significantly decreased in SKOV3 cells with low levels of MGRN1 expression. Similarly, EGR1 mRNA expression was lower in platinum-resistant EOC patients and was positively correlated with MGRN1 mRNA expression. Conclusion: The hypermethylation of the MGRN1 promoter region and low expression of MGRN1 were associated with platinum resistance in EOC patients.