Browsing by Subject "Promoter methylation"

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    Hypomethylation-mediated overexpression of ITGA2 stimulates cell invasion and migration of thyroid carcinoma
    (Universidad de Murcia. Servicio de publicaciones, 2023) Chen, Hong; Zhang, Chunying; Li, Yanbing; Chen, Chunyou
    Objective. To study the molecular mechanism of DNA methylation-mediated ITGA2 overexpression in thyroid carcinoma (TC). Methods. First, 450K methylation data and mRNA expression profiles in TCGA-THCA dataset were downloaded from TCGA database. ITGA2 was identified as a methylation-driven gene by using R package “MethylMix”. Afterwards, qRT-PCR, western blot and flow cytometry assay were performed to measure ITGA2 expression in TC cells. Methylationspecific PCR was utilized to measure promoter region methylation of ITGA2 in TC cells. Transwell and wound healing assays were carried out to assess cell invasive and migratory properties. Results. Compared with normal cells, TC cells presented significantly increased ITGA2 expression. In addition, ITGA2 expression was controlled by DNA methylation. Hypomethylation of CpG island resulted in an increased ITGA2 expression. Hence, methylation and expression levels of ITGA2 were inversely associated. Moreover, overexpression of ITGA2 and promoter region hypomethylation facilitated cell invasive and migratory abilities in TC. Conclusion. These findings authenticated that promoter region hypomethylation of ITGA2 fostered ITGA2 expression as well as TC cell invasion and migration.
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    Promoter methylation of tumor-related genes in gastric carcinogenesis
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Zhao, Chenghai; Bu, Xianmin
    Aberrant promoter methylation and subsequent silencing of cancer-related genes has been recognized as an important pathway involved in gastric carcinogenesis. In fact, several factors are believed to contribute to its induction in gastric epithelia, including aging, diet, chronic inflammation and infection of Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV). However, the underling mechanisms are not completely identified, despite the belief that increased expression or activity of DNA methyltransferases (DNMTs), or decreased demethylation activity may contribute to the excessive methylation. A great number of genes with promoter methylation have been observed in gastric cancer (GC), among which p16INK4A (p16), Mut L homologue 1 (MLH1), Epithelial-cadherin (E-cadherin), Runt-related transcription factor 3 (RUNX3), adenomatous polyposis coli (APC), O(6)-methylguanine-DNA methyltransferase (MGMT), Ras association domain family 1A (RASSF1A) and Death-associated protein kinase (DAPK) have been extensively studied. Unlike the distinct methylation characterization in single genes, methylation analysis of multiple genes may provide more information in risk prediction, early detection, prognosis assessment and chemotherapy choice for GC. Specifically, particular monitoring and screening should be performed on those over 45 years old, with precancerous gastric disease or infection of H. pylori or EBV. As an alternative to tumor tissues, methylation detection in patient sera or gastric washes may also be used in risk prediction and early detection. However, what still poses a great challenge as well as a puzzle is the determination of the very genes that should be used in methylation analysis. Because epigenetic alterations are normally reversible, drugs or chemical compounds with demethylating activity, such as 5-aza-2’-deoxycytidine (5-aza-dC) could be used in the treatment of patients with multiple gene methylation. In view of the adverse effects of 5-aza-dC, DNMT-targeted strategy has been proposed and may prove to be more effective than demethylating agents.