ArticleBMC cancer2015
DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
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- The MAL Family of Proteins: Normal Function, Expression in Cancer, and Potential Use as Cancer Biomarkers.Cancers · 2023Review
- Role of epigenetics and the transcription factor Sp1 in the expression of the D prostanoid receptor 1 in human cartilage.Frontiers in cell and developmental biology · 2023Article
- Hypermethylation-Mediated Silencing ofInternational journal of molecular sciences · 2022Article
- Myelin and lymphocyte protein serves as a prognostic biomarker and is closely associated with the tumor microenvironment in the nephroblastoma.Cancer medicine · 2022Article
- The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer.Cells · 2021Review
- Runx3 Induces a Cell Shape Change and Suppresses Migration and Metastasis of Melanoma Cells by Altering a Transcriptional Profile.International journal of molecular sciences · 2021Article
- Myelin and Lymphocyte Protein (MAL): A Novel Biomarker for Uterine Corpus Endometrial Carcinoma.Cancer management and research · 2021Article
- Clinical Significance of a Novel Tumor Progression-Associated Immune Signature in Colorectal Adenocarcinoma.Frontiers in cell and developmental biology · 2021Article
- FANCF hypomethylation is associated with colorectal cancer in Han Chinese.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2020Article
- Comprehensive RNA Sequencing in Adenoma-Cancer Transition Identified Predictive Biomarkers and Therapeutic Targets of Human CRC.Molecular therapy. Nucleic acids · 2020Article
- Article
- Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation.Journal of translational medicine · 2020Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) development is accompanied by changes in expression for several genes; but the details of the underlying regulatory procesess remain unknown. Our aims were to assess the role of epigenetic processes in tumour formation and to identify characteristic DNA methylation and miRNA alterations in the colorectal adenoma-carcinoma sequence.
methodsWhole genome expression profiling was performed on colonic biopsy samples (49 healthy normal, 49 colorectal adenoma (AD), 49 CRC); on laser capture microdissected (LCM) epithelial and stromal cells from 6 CRC-normal adjacent tissue (NAT) samples pairs, and on demethylated human CRC cell lines using HGU133 Plus 2.0 microarrays (Affymetrix). Methylation status of genes with gradually altering expression along the AD-CRC sequence was further analysed on 10-10 macrodissected and 5-5 LCM samples from healthy colon, from adenoma and from CRC biopsy samples using bisulfite-sequencing PCR (BS-PCR) followed by pyrosequencing. In silico miRNA prediction for the selected genes was performed with miRWALK algorithm, miRNA expression was analysed on 3 CRC-NAT sample pairs and 3 adenoma tissue samples using the Human Panel I + II (Exiqon). SFRP1 immunohistochemistry experiments were performed.
resultsA set of transcripts (18 genes including MAL, SFRP1, SULT1A1, PRIMA1, PTGDR) showed decreasing expression (p < 0.01) in the biopsy samples along the adenoma-carcinoma sequence. Three of those (COL1A2, SFRP2, SOCS3) showed hypermethylation and THBS2 showed hypomethylation both in AD and in CRC samples compared to NAT, while BCL2, PRIMA1 and PTGDR showed hypermethylation only in the CRC group. miR-21 was found to be significantly (p < 0.01) upregulated in adenoma and tumour samples compared to the healthy colonic tissue controls and could explain the altered expression of genes for which DNA methylation changes do not appear to play role (e.g. BCL2, MAL, PTGS2). Demethylation treatment could upregulate gene expression of genes that were found to be hypermethylated in human CRC tissue samples. Decreasing protein levels of SFRP1 was also observed along the adenoma-carcinoma sequence.
conclusionHypermethylation of the selected markers (MAL, PRIMA1, PTGDR and SFRP1) can result in reduced gene expression and may contribute to the formation of colorectal cancer.
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