Epigenetic silencing of <i>NDRG2</i> promotes colorectal cancer proliferation and invasion

Hong, Sung Noh; Kim, Sung Jin; Kim, Eun-Ran; Chang, Dong Kyung; Kim, Young‐Ho

doi:10.1111/jgh.13068

Cited by 18 publications

(26 citation statements)

References 22 publications

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“…Hong and collaborators found that epigenetic silencing of NDRG2 induced proliferation and invasion of primary colorectal cancer cells, and that this could be associated with advanced stages of the disease (49). Similarly, Lee and collaborators found that in patients with gallbladder carcinoma loss of NDRG2 expression was an independent predictor of decreased patient survival and was significantly associated with a more advanced tumor stage (32).…”

Section: Discussionmentioning

confidence: 99%

A 22q11.2 amplification in the region encoding microRNA-650 correlates with the epithelial to mesenchymal transition in breast cancer primary cultures of Mexican patients

Lango-Chavarría

Chimal-Ramírez

Ruiz‐Tachiquín

et al. 2017

International Journal of Oncology

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Breast cancer ranks first in incidence and mortality in working age women. Cancer initiation and progression relies on accumulation of genetic and epigenetic aberrations that alter cellular processes, among them, epithelial to mesenchymal transition (EMT) denotes particularly aggressive neoplasias given its capacity to invade and metastasize. Several microRNAs (miRNA) have been found able to regulate gene expression at the core of EMT. In this study, the Affymetrix CytoScan HD array was used to analyze three different primary tumor cell isolates from Mexican breast cancer patients. We found an amplification in band 22q11.2 shared by the three samples, in the region that encodes miRNA-650. Overexpression of this miRNA has been associated with downregulation of tumor suppressors ING4 and NDRG2, which have been implicated in cancer progression. Using the Pathway Linker platform the ING4 and NDRG2 interaction networks showed a significant association with signaling pathways commonly deregulated in cancer. Also, several studies support their participation in the EMT. Supporting the latter, we found that the three primary isolates were E-cadherin negative, vimentin positive, presented a cancer stem cell-like phenotype CD44+CD24−/low and were invasive in Transwell invasion assays. This evidence suggests that the gain of region 22q11.2 contributes to trigger EMT. This is the first evidence linking miR-650 and breast cancer.

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Section: Discussionmentioning

confidence: 99%

A 22q11.2 amplification in the region encoding microRNA-650 correlates with the epithelial to mesenchymal transition in breast cancer primary cultures of Mexican patients

Lango-Chavarría

Chimal-Ramírez

Ruiz‐Tachiquín

et al. 2017

International Journal of Oncology

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“…SW480 and SW620) show minimal NDRG1 CpG island methylation [53] and a number of GI-cancer cell lines and colon cancer tissues show variable NDRG2 promoter hypermethylation at several CpG sites, with levels ranging between 27 to 100% [45,[57][58][59][60]. Promoter hypermethylation of NDRG2 corresponds well with reduced NDRG2 expression in CRC [45,[57][58][59][60]. In fact, 84-100% of the hypermethylated tissues lack NDRG2 mRNA expression and immunoreactivity [57][58][59].…”

Section: Epigenetic Changesmentioning

confidence: 99%

“…Promoter hypermethylation of NDRG2 corresponds well with reduced NDRG2 expression in CRC [45,[57][58][59][60]. In fact, 84-100% of the hypermethylated tissues lack NDRG2 mRNA expression and immunoreactivity [57][58][59]. The differential methylation pattern could be explained by the presence of several transcription start sites (TSS) with distinct promoters having CpG islands, primarily located in exon 1 and 2 of the NDRG2 gene [50], and the use of different primer sequences to analyze the methylation status of the NDRG2 promoter [45,50,58,59,61].…”

Section: Epigenetic Changesmentioning

confidence: 99%

A combined literature and in silico analysis enlightens the role of the NDRG family in the gut

Vaes

Schonkeren

Brosens

et al. 2018

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Also, NDRG2 upregulation was associated with Alzheimer's disease or cerebral ischemia [21, 22]. Several studies have shown NDRG2 promoter CpG island methylation and down-regulation in liver [13], gastric [10], colorectal cancers (CRC) [23, 24], glioblastomas [8, 9] and anaplastic meningioma [25]. However, NDRG2 promoter methylation and mRNA expression levels in PAs has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

N-myc downstream-regulated gene 2 (NDRG2) promoter methylation and expression in pituitary adenoma

et al. 2017

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BackgroundPituitary adenoma (PA) is a benign primary tumor that arises from the pituitary gland and is associated with ophthalmological, neurological and endocrinological abnormalities. However, causes that increase tumor progressing recurrence and invasiveness are still undetermined. Several studies have shown N-myc downstream regulated gene 2 (NDRG2) as a tumor suppressor gene, but the role of NDRG2 gene in pituitary adenoma pathogenesis has not been elucidated. The aim of our research has been to examine NDRG2 mRNA expression in PA and to determine the associations between the NDRG2 gene epigenetic changes and the development of recurrence or invasiveness of PA and patient clinical data.MethodsThe MS-PCR was used for NDRG2 promoter methylation analysis and gene mRNA expression levels were evaluated by qRT-PCR in 68 non-functioning and 73 functioning adenomas. Invasiveness was evaluated using magnetic resonance imaging with Hardy’s modified criteria. Statistical analysis was performed to find correlations between NDRG2 gene mRNA expression, promoter methylation and patient clinical characteristics and PA activity.ResultsThe NDRG2 mRNA expression was significantly lower in the case of acromegaly (GH and IGF-1 hypersecretion) than in other diagnoses of PAs (p < 0.05). Also, the NDRG2 expression was significantly higher in prolactinoma (PRL hypersecretion) than in in other diagnoses of PAs (p < 0.05). The promoter of NDRG2 was methylated in 22.69% (12/58 functioning and 15/61 non-functioning) of patients with PA. However, the NDRG2 gene mRNA expression was not significantly related to its methylation status. Clinical factors, such as: age, gender, relapse and diagnoses of Cushing syndrome were of no significance for NDRG2 promoter methylation and mRNA expression levels, as well as secreting or non-secreting PAs and the invasiveness of PAs.ConclusionThe different NDRG2 promoter methylation and expression levels in PA samples showed tumor heterogeneity and indicates a potential role of this gene in pituitary adenoma pathogenesis, but the corresponding details require intensive research.

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Epigenetic silencing of NDRG2 promotes colorectal cancer proliferation and invasion

Abstract: Epigenetic silencing of NDRG2 induces proliferation and invasion of CRC and may be associated with proximal CRC and advanced T stage. NDRG2 methylation might serve as novel biomarker of CRC.

Cited by 18 publications

References 22 publications

A 22q11.2 amplification in the region encoding microRNA-650 correlates with the epithelial to mesenchymal transition in breast cancer primary cultures of Mexican patients

A 22q11.2 amplification in the region encoding microRNA-650 correlates with the epithelial to mesenchymal transition in breast cancer primary cultures of Mexican patients

A combined literature and in silico analysis enlightens the role of the NDRG family in the gut

N-myc downstream-regulated gene 2 (NDRG2) promoter methylation and expression in pituitary adenoma

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