Aberrant epigenetic regulation of GABRP associates with aggressive phenotype of ovarian cancer

Experimental & Molecular Medicine
Hye Youn SungJung Hyuck Ahn

Abstract

Metastasis is a major cause of therapeutic failure in ovarian cancer. To elucidate molecular mechanisms of ovarian cancer metastasis, we previously established a metastatic xenograft mouse model using human ovarian carcinoma SK-OV-3 cells. Using gene expression profiling, we found that γ-aminobutyric acid (GABA)Areceptor π subunit (GABRP) expression was upregulated (>4-fold) in metastatic tissues from our xenograft mice compared with SK-OV-3 cells. Importantly, GABRP knockdown diminished the migration and invasion of SK-OV-3 cells, and reduced extracellular signal-regulated kinase (ERK) activation while overexpression of GABRP exhibited significantly increased cell migration, invasion and ERK activation. Moreover, treatment with the mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor U0126 similarly suppressed the migration and invasion of SK-OV-3 cells, implying that GABRP promotes these cellular behaviors by activating the MAPK/ERK pathway. Using genome-wide DNA methylation profiling, we identified hypomethylated CpG sites in the GABRP promoter in metastatic tissues from the xenograft mice compared with SK-OV-3 cells. Treatment with a DNA methyltransferase inhibitor demonstrated that methylation at -963 bp from...Continue Reading

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Citations

Sep 19, 2019·Oncogene·Shu-Heng JiangZhi-Gang Zhang
Feb 28, 2020·Experimental and Therapeutic Medicine·Yan-Jun GuoLing-Ling Hu
Oct 15, 2019·Frontiers in Cell and Developmental Biology·Alka SinghManisha Sachan
Mar 9, 2019·Molecular and Clinical Oncology·Julie L HentzeEstrid V Høgdall
Oct 22, 2018·Life Sciences·Pella Cecilia SöderhielmAnders A Jensen
Aug 17, 2021·Frontiers in Cell and Developmental Biology·Yiyi LiangHong Tu
Oct 16, 2021·Experimental Biology and Medicine·Debanjan BhattacharyaSoma Sengupta

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Methods Mentioned

BETA
xenograft
PCR
xenografts
transfection
electrophoresis
methylation profiling
methylation

Software Mentioned

qMSP
GraphPad Prism
MethPrimer
Image Gauge
Affymetrix
Bioconductor ‘ affy ' package (

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