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pmid:33494187

ROR2 Is Epigenetically Regulated in Endometrial Cancer.

Dongli Liu · Luis Enriquez · Caroline E Ford

Cancers · 2021 doi:10.3390/cancers13030383

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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ROR2 Is Epigenetically Regulated in Endometrial Cancer.
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10.3390/cancers13030383
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Dongli Liu
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Luis Enriquez
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Caroline E Ford
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2021
abstract
The Wnt signalling receptor ROR2 has been identified as a possible therapeutic target in numerous cancers; however, its exact role remains unclear. The aim of this study was to investigate the role of ROR2 in endometrial cancer (EC) and the potential mechanism associated with its altered expression. The association between ROR2 mRNA expression levels and clinicopathological parameters, including overall survival (OS), in EC was analysed in The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) cohort and GEO dataset GSE17025. Four EC cell lines (KLE, MFE-296, Ishikawa and ARK-1) and eight clinical EC samples were analysed for ROR2 methylation via Combined Bisulphite Restriction Analysis (COBRA) and bisulphite genomic sequencing (BGS). In addition, the functional effects of ROR2 overexpression were investigated in Ishikawa and ARK-1 cells following ectopic ROR2 expression. ROR2 promoter methylation or reduced ROR2 expression were both found to correlate with shorter OS, high grade and serous subtype in the TCGA-UCEC and GEO datasets. ROR2 was epigenetically silenced by promoter methylation in both patient samples and cell lines. A significant correlation between ROR2 expression levels and promoter methylation was observed in patient samples (r = -0.797, p = 0.018). ROR2 restoration in ARK-1 significantly decreased invasion ability, with associated changes in epithelial-mesenchymal transition (EMT) markers. ROR2 plays a tumour-suppressor role in EC and is epigenetically suppressed with the development of disease. It may represent a diagnostic or therapeutic candidate for EC.
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ade endometrioid cell lines. Both qRTPCR and Western blot consistently showed undetectable ROR2 expres
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fessor Kyle Hoehn (UNSW, Sydney, Australia). Cell lines were maintained in medium containing 10% foetal bovine serum
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