Significant association between KDM1A promoter hypomethylation and colorectal cancer in Han Chinese
| Autor: | Xiuru Ying, Boyi Wu, Jieer Ying, Dongping Wu, Jie Zhong, Cong Zhou, Shiwei Duan, Ranran Pan |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Genotype Colorectal cancer medicine.disease_cause Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Asian People medicine Humans Genetic Predisposition to Disease Promoter Regions Genetic Aged Histone Demethylases Regulation of gene expression biology business.industry KDM1A Cell Biology Methylation DNA Methylation Middle Aged medicine.disease Fold change 030104 developmental biology Histone 030220 oncology & carcinogenesis biology.protein Cancer research Demethylase Female Colorectal Neoplasms business Carcinogenesis |
| Zdroj: | Pathology - Research and Practice. 215:532-538 |
| ISSN: | 0344-0338 |
| DOI: | 10.1016/j.prp.2018.12.005 |
| Popis: | Lysine-specific histone demethylase 1A gene (KDM1A) promotes tumorigenesis. The aim of this study was to investigate the association between KDM1A methylation and colorectal cancer (CRC). Currently, we collected 37 paired CRC tissues and adjacent non-tumor tissues from Jiangsu province and 75 paired CRC tissues and adjacent non-tumor tissues from Zhejiang province to conduct a two-stage experiment to study the association between KDM1A methylation and CRC. We used qMSP to measure the KDM1A promoter methylation, and the percentage of methylation reference (PMR) to quantify the KDM1A promoter methylation level. To investigate the effect of the selected KDM1A fragment on gene expression regulation, we also performed a dual luciferase reporter gene assay. In the stage I study, the KDM1A promoter methylation level in CRC tumor tissues was significantly lower than that in adjacent non-tumor tissues (median PMR: 6.93% vs 10.25%, P = 0.033). The results of the stage II study were similar to those of the stage I study (mean PMR: 12.94% versus 17.42%, P = 0.016). In addition, a clinical pathology subgroup analysis found that KDM1A hypomethylation was associated with CRC only in patients with well-differentiated CRC (stage I: P = 0.047; stage II: P = 0.040). The dual luciferase reporter assay showed that the transcriptional activity of the recombinant pGL3-KDM1A plasmid was significantly higher (fold change = 2, P = 0.0009). In conclusion, our results suggest that KDM1A hypomethylation is significantly associated with CRC. |
| Databáze: | OpenAIRE |
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