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Omics · study · 2026

Methylation profiling in colorectal cancer: colorectal cancers vs. adjacent normal colon tissues

Listed in NCBI GEO

Dysregulation of cellular metabolism is one of the hallmarks of cancer.

Description

Tumor cells would enhance glycolysis to fuel the phenotypes of rapid proliferation and invasion. This study aims to explore epigenetic reprogramming of glycolysis pathway in colorectal cancer (CRC).

CRCs and the adjacent normal colon tissues were profiled by using a comprehensive methylation array (Illumina Methylation EPIC Beadchips) to comprehensively analyze the methylation alterations in the glycolysis pathway. Differentially methylated genes (DMGs) were identified by using β value difference (≧ 0.2 or ≦ -0.2) and Wilcoxon rank-sum test (p < 0.05), and the common DMG in open datasets (GSE42752, GSE25062 and TCGA).

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Pyrosequencing was executed to validate the DMGs. Hexokinase domain containing 1 (HKDC1), the major hypomethylated gene we found, was overexpressed in colon cancer cells. Cells were treated with an HKDC1 inhibitor to elucidate the role of HKDC1.

We found hypomethylation of HKDC1 was the only shared hypomethylated DMG in glycolysis pathway after comparing our methylation profiles of CRC to 3 public datasets. The RT-qPCR study in our cohort supported HDKC1 expression is methylation-regulated. Overexpression of HKDC1 in colon cancer cells resulted in increased proliferation of colon cancer cells and decreased cytotoxicity by an HKDC1 inhibitor.

RNA sequencing revealed significant up-regulation of glycolysis and cell cycle pathways and their targets in HKDC1 overexpressed cells. In summary, hypomethylation of HKDC1 is common in CRC and may regulate cellular metabolism to promote proliferation of colon cancer cells through upregulation of glycolysis and cell cycle pathways.

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Topics

From keywords
Life Sciences
Inferred from text
Cancer 75% · DNA methylation profiling 65% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 11 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE3090028 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:methylation-profiling-by-genome-tiling-arraysource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[method].local:method:dna-methylation-profilingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title