Thus, DNMT3A-mediated hypermethylation suppressed miR-639 expression, derepressing the expression of MSYT2 and ZEB1, which promoted tumorigenesis of liver cancer.
Although aberrant DNA methyltransferase 3a (DNMT3a) expression is important to the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC), the role of DNMT3a in PDAC prognosis is not clarified yet due to the limited studies and lacking of underlying molecular mechanism.
A myriad of protein partners modulate the activity of the human DNA methyltransferase 3A (DNMT3A), whose interactions with these other proteins are frequently altered during oncogenesis.
Genome-wide miRNA sequencing data of 990 patients from The Cancer Genome Atlas (TCGA) dataset and 148 patients from China cohort were analyzed to excavate the pathogenic implications of miR-708-5p.<b>Results:</b> Expression of miR-708-5p inhibits the CSC traits of NSCLC cells <i>in vitro</i> while antagonizing miR-708-5p promotes tumorigenesis <i>in vivo</i> miR-708-5p directly suppresses the translation of DNMT3A, which results in a substantial reduction of global DNA methylation and the upregulated expression of tumor suppressor CDH1.
By recruiting DNMT3a to suppress the expression of MIR137 that targets GLS1 mRNA, HSF1 stimulated GLS1-dependent mTOR activation to promote colorectal carcinogenesis.
Altogether, we demonstrate that Dnmt3a and Dnmt3b protect the epidermis from tumorigenesis and that squamous carcinomas are sensitive to inhibition of PPAR-γ.
Taken together, these observations demonstrates a novel epigenetic feedback loop between miR-200c and DNMT3a in the carcinogenesis and progression of GC.
Consistently, over-expression of DNMT3a inhibits the miR-182-induced apoptosis, and inhibition of DNMT3a promotes cervical cancer cell apoptosis, which further demonstrated that DNMT3a involved in cervix carcinogenesis.
The expression of DNMT3A/B increased at the initial stages of oncogenesis and the expression of DNMT1 and HAT1 decreased at the advanced stages of breast cancer.
DNA-methyltransferase (DNMT)-3A which contains DNMT3A1 and DNMT3A2 isoforms have been suggested to play a crucial role in carcinogenesis and showed aberrant expression in most cancers.
These findings support that the loss or suppression of miR-101 function accelerates lung tumorigenesis through DNMT3a-dependent DNA methylation, and suggest that miR-101-DNMT3a axis may have therapeutic value in treating refractory lung cancer.
Also, the data suggest that DNMT3A is altered in many cancer types by various ways, including somatic mutations, allelic loss and loss of expression that might play roles in tumorigenesis.
Here, we investigated the expression of DNA demethylase and three DNA methyltransferases during colorectal tumorigenesis comparing the genes encoding DNA methyltransferases 1 (DNMT1), 3A, and 3B (DNMT3A and DNMT3B) with methyl-CpG binding domain protein 2 (MBD2), recently described as the only active DNA demethylase.