ArticlePloS one2014
Hypermethylation leads to bone morphogenetic protein 6 downregulation in hepatocellular carcinoma.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- NSUN6 Maintains BMPER Stability in an m5C-Dependent Manner to Suppress Cell Proliferation and Migration in Hepatocellular Carcinoma.Biology of the cell · 2025Article
- BMP6 inhibits gastric cancer growth and predicts good prognosis.Journal of gastrointestinal oncology · 2024Article
- Interplay between gut microbiota and the master iron regulator, hepcidin, in the pathogenesis of liver fibrosis.Pathogens and disease · 2024Review
- HIF2α, Hepcidin and their crosstalk as tumour-promoting signalling.British journal of cancer · 2023Review
- Hepcidin in hepatocellular carcinoma.British journal of cancer · 2022Review
- Hepcidin Downregulation Correlates With Disease Aggressiveness And Immune Infiltration in Liver Cancers.Frontiers in oncology · 2021Article
- [Progress on epigenetic regulation of iron homeostasis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Review
- Article
- Differential regulation of hepcidin in cancer and non-cancer tissues and its clinical implications.Experimental & molecular medicine · 2018Review
- Dragon (repulsive guidance molecule b, RGMb) is a novel gene that promotes colorectal cancer growth.Oncotarget · 2015Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn the liver, bone morphogenetic protein 6 (BMP-6) maintains balanced iron metabolism. However, the mechanism that underlies greater BMP-6 expression in hepatocellular carcinoma (HCC) tissue than adjacent non-cancerous tissue is unclear. This study sought to investigate the epigenetic mechanisms of BMP-6 expression by analysing the relationship between the DNA methylation status of BMP-6 and the expression of BMP-6.
methodsMethylation-specific polymerase chain reaction (PCR), bisulphite sequencing PCR, the MethyLight assay, and quantitative real-time PCR were performed to examine BMP-6 methylation and mRNA expression levels. Immunohistochemistry (IHC) was performed on tissue arrays to evaluate the BMP-6 protein level.
resultsBMP-6 mRNA expression was approximately 84.09% lower in HCC tissues than in adjacent non-cancerous tissues, and this low level of expression was associated with a poor prognosis. Moreover, the hypermethylation observed in HCC cell lines and HCC tissues was correlated with the BMP-6 mRNA expression level, and this correlation was validated following treatment with 5-aza-CdR, a demethylation agent. In addition, BMP-6 DNA methylation was upregulated by 68.42% in 114 clinical HCC tissue samples compared to adjacent normal tissues, whereas the BMP-6 staining intensity was downregulated by 77.03% in 75 clinical HCC tissue samples in comparison to adjacent normal tissues. Furthermore, elevated expression of BMP-6 in HCC cell lines inhibited cell colony formation.
conclusionsOur results suggest that BMP-6 CpG island hypermethylation leads to decreased BMP-6 expression in HCC tissues.
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