Epigenetic regulation of putative tumor suppressor TGFBI in human leukemias

• Published in: Chinese medical journal Vol. 127; no. 9; pp. 1645 - 1650
• Main Authors: Fang, Hongbo, Liu, Jing, Guo, Dan, Liu, Peixiang, Zhao, Yongliang
• Format: Journal Article
• Language: English
• Published: China by Lippincott Williams & Wilkins, Inc 05.05.2014; Center for Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China%Center for Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences,Beijing 100049, China%Department of Clinical Laboratory, First People's Hospital of Yueyang, Yueyang, Hunan 414000, China
• Subjects: Cell Line, Tumor; CpG Islands - genetics; DNA Methylation - drug effects; DNA Methylation - genetics; Epigenesis, Genetic - drug effects; Epigenesis, Genetic - genetics; Extracellular Matrix Proteins - genetics; Humans; Leukemia - epidemiology; PCR方法; Promoter Regions, Genetic - genetics; Reverse Transcriptase Polymerase Chain Reaction; Sulfites - pharmacology; Transforming Growth Factor beta - genetics; 人类; 去甲基化; 外周血单核细胞; 实时定量RT-PCR; 白血病细胞系; 表观; 遗传调控; leukemia; TGFBI; methylation-specific PCR; hypermethylation
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.20133015

Background Both in vitro and in vivo data have demonstrated the TGFBI gene functions as a putative tumor suppressor and is frequently downregulated in human tumors of different histological types.The hypermethylation of the TGFBI promoter,as one of the main regulatory mechanisms,is associated with TGFBI silencing.In this study,we used a methylation-specific PCR （MSP） method to evaluate the methylation status of the TGFBI promoter in human leukemias.Methods Real-time RT-PCR and methylation-specific PCR approaches were performed to define the TGFBI expression and promoter methylation in human leukemia call lines and clinical samples.Genomic DNA was isolated from peripheral blood mononuclear cells from leukemia patients,bisulfite-converted,and analyzed by the MSP method.Results Hypermethylation of the TGFBI promoter occurred in leukemia cell lines and demethylation treatment reexpressed TGFBI at a substantially increased level in most of leukemia cell lines tested.Furthermore,a much higher level of CpG island methylation and a significantly lower TGFBI expression were also identified in clinical leukemia samples.Conclusion The results suggest an important role of promoter methylation in regulating TGFBI expression in leukemia,which provides a useful diagnostic marker for clinical management of human leukemias.