scholarly journals Knockdown of DNA methyltransferase-1 inhibits proliferation and derepresses tumor suppressor genes in myeloma cells

2014 ◽  
Vol 8 (5) ◽  
pp. 2130-2134 ◽  
Author(s):  
WENWEN ZHOU ◽  
HUYING CHEN ◽  
XIULI HONG ◽  
XIAOQING NIU ◽  
QUANYI LU
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Suppressor Genes ◽  
Myeloma Cells ◽  
Methyltransferase 1

scholarly journals RX-3117 (Fluorocyclopentenyl-Cytosine)-Mediated Down-Regulation of DNA Methyltransferase 1 Leads to Protein Expression of Tumor-Suppressor Genes and Increased Functionality of the Proton-Coupled Folate Carrier

2020 ◽  
Vol 21 (8) ◽  
pp. 2717 ◽  
Author(s):  
Dzjemma Sarkisjan ◽  
Joris R. Julsing ◽  
Btissame El Hassouni ◽  
Richard J. Honeywell ◽  
Ietje Kathmann ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Protein Expression ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Functional Assay ◽  
Dna Methyltransferase 1 ◽  
Suppressor Genes ◽  
Resistant Variant ◽  
E Cadherin ◽  
Methyltransferase 1

(1) Background: RX-3117 (fluorocyclopentenyl-cytosine) is a cytidine analog that inhibits DNA methyltransferase 1 (DNMT1). We investigated the mechanism and potential of RX-3117 as a demethylating agent in several in vitro models. (2) Methods: we used western blotting to measure expression of several proteins known to be down-regulated by DNA methylation: O6-methylguanine-DNA methyltransferase (MGMT) and the tumor-suppressor genes, p16 and E-cadherin. Transport of methotrexate (MTX) mediated by the proton-coupled folate transporter (PCFT) was used as a functional assay. (3) Results: RX-3117 treatment decreased total DNA-cytosine-methylation in A549 non-small cell lung cancer (NSCLC) cells, and induced protein expression of MGMT, p16 and E-cadherin in A549 and SW1573 NSCLC cells. Leukemic CCRF-CEM cells and the MTX-resistant variant (CEM/MTX, with a deficient reduced folate carrier) have a very low expression of PCFT due to promoter hypermethylation. In CEM/MTX cells, pre-treatment with RX-3117 increased PCFT-mediated MTX uptake 8-fold, and in CEM cells 4-fold. With the reference hypomethylating agent 5-aza-2′-deoxycytidine similar values were obtained. RX-3117 also increased PCFT gene expression and PCFT protein. (4) Conclusion: RX-3117 down-regulates DNMT1, leading to hypomethylation of DNA. From the increased protein expression of tumor-suppressor genes and functional activation of PCFT, we concluded that RX-3117 might have induced hypomethylation of the promotor.

scholarly journals MUC1-C induces DNA methyltransferase 1 and represses tumor suppressor genes in acute myeloid leukemia

Oncotarget ◽  
2016 ◽  
Vol 7 (26) ◽  
pp. 38974-38987 ◽  
Author(s):  
Ashujit Tagde ◽  
Hasan Rajabi ◽  
Dina Stroopinsky ◽  
Reddy Gali ◽  
Maroof Alam ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Myeloid Leukemia ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Suppressor Genes ◽  
Acute Myeloid ◽  
Methyltransferase 1

scholarly journals MicroRNA-148b and microRNA-152 reactivate tumor suppressor genes through suppression of DNA methyltransferase-1 gene in pancreatic cancer cell lines

2014 ◽  
Vol 15 (4) ◽  
pp. 419-427 ◽  
Author(s):  
Masoumeh Azizi ◽  
Ladan Teimoori-Toolabi ◽  
Mohsen Karimi Arzanani ◽  
Kayhan Azadmanesh ◽  
Pezhman Fard-Esfahani ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Dna Methyltransferase 1 ◽  
Suppressor Genes

scholarly journals Targeting DNA methylation for treating triple-negative breast cancer

2019 ◽  
Vol 20 (16) ◽  
pp. 1151-1157 ◽  
Author(s):  
Jia Yu ◽  
Jacqueline Zayas ◽  
Bo Qin ◽  
Liewei Wang
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Triple Negative ◽  
Suppressor Genes ◽  
Dna Methyltransferase Inhibitors

Triple-negative breast cancer (TNBC) accounts for 15–20% of all invasive breast cancers and tends to have aggressive histological features and poor clinical outcomes. Unlike, estrogen receptor- or HER2-positive diseases, TNBC patients currently lack the US FDA-approved targeted therapies. DNA methylation is a critical mechanism of epigenetic modification. It is well known that aberrant DNA methylation contributes to the malignant transformation of cells by silencing critical tumor suppressor genes. DNA methyltransferase inhibitors reactivate silenced tumor suppressor genes and result in tumor growth arrest, with therapeutic effects observed in patients with hematologic malignancies. The antitumor effect of these DNA methyltransferase inhibitors has also been explored in solid tumors, especially in TNBC that currently lacks targeted therapies.

Antitumor Activity of Cda-2, An Extract from Unine, in a High-Risk Myelodysplastic Syndrome Cells in Vitro

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5099-5099
Author(s):  
Lin Qiu ◽  
Xiao-dan Wang ◽  
Bing-hong Han ◽  
Zhao-min Zhan ◽  
Zhang Bo-long ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
High Risk ◽  
Tumor Suppressor ◽  
Myelodysplastic Syndrome ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Dependent Manner ◽  
Suppressor Genes ◽  
Specific Pcr

Abstract DNA methyltransferase inhibitors (DNMTI), including 5-azacytidine and 5-aza-2′- deoxycytidine, are a new class of epigenetic drug, which exhibit higher response rates in myelodysplastic syndrome (MDS) patients. Cell differentiation agent (CDA-2) is a kind of urine extracts, which contains several DNMTIs. A phase IV clinical trials for MDS showed total response rate is 69.22%. In the present study, we investigated the mechanism of CDA-2 on MDS using high-risk MDS cell line namely MuTz-1. MTT assay results showed that CDA-2 significantly inhibit the cell growth at a dose and time-dependent manner. Flow cytometer anlyasis showed that this growth inhibition was remarkblely associated with cycle arrest in G1-phase, but not associated with apoptosis. In addition, CDA-2 increased the expression of CD11b/CD14, a pair markers representing cell differentiation. we found the spectrum of hypermethylated tumor suppressor genes (TIMP3, CDKN2B, CHFR, CD44, RASSF1, TP73, IGSF4, CDH13 and DAPK) in MuTz-1 cells by Methylation-Specific Multiplex ligation-dependent Probe amplification (MS-MLPA), but the hypermethylation of these genes were remarkable decreased, as well as the expressions of DNA methyltransferase genes DNMT1 and DNMT3B at mRNA and protein level were downregulated in the treatment for 3 days with CDA-2. Also, we used CDA-2 for treatment of three MDS patients, whose several tumor suppressor genes are hypermethylated. After tour weeks of treatment, all the hypermethylation genes were undetected, part of this result was verified by methylation specific PCR (MSP) and bisulphite sequencing. In conclusion, our results demonstrated that CDA-2 may be an effective agent targeting hepermethylated tumor suppressor genes on MDS.

DNA Methylation Changes Following 5-Azacitidine Treatment in Patients with Myelodysplastic Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2791-2791
Author(s):  
Huong Thi Thanh Tran ◽  
Hee Nam Kim ◽  
Yeo-Kyeoung Kim ◽  
Jae-Sook Ahn ◽  
Il-Kwon Lee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Conflicts Of Interest ◽  
Control Group ◽  
Disease Pathogenesis ◽  
Suppressor Genes ◽  
Clinical Responses ◽  
Dependent Probe

Abstract Abstract 2791 Poster Board II-767 Gene silencing by promoter methylation is as potent as functional inactivating of tumor suppressor genes by mutations. DNA methyltransferase inhibitor, 5-azacytidine (AC) and 5-aza-2 -deoxycitidine (DAC), which is proved to be effective in myelodysplastic syndromes (MDS) can induce re-expression in cancer; however their mechanism remains controversial. 25 tumor suppressor genes by MS-MLPA (methylation-specific multiplex ligation-dependent probe amplification) were analyzed in 44 MDS patients treated Vidaza® (5-azacitidine, AC). Hypermethylation of at least one gene was detected in 9/44 patients (20.5%), including four genes CDKN2B, FHIT, ESR1 and IGSF4. Interestingly, of 9 hypermethylated patients, 8 patients showed demethylation in concordance with their clinical responses after three to five cycles AC treatment. Lack or decrease methylation was observed in four patients with hematological improvements. Persistence methylation was observed in four others who became AML transformation or no response after treatment, especially reinforcing methylated gene in a case progressed to leukemia later. Our study also founds out IGSF4 gene hypermethylation in MDS as a first report. Additionally, mRNA expression of CDKN2B, IGSF4, and ESR1 in MDS were significantly lower than those in the control group (p < 0.05). Our results suggest that the methylation changes of specific genes contributes to disease pathogenesis and might present a molecular marker that can be used to monitor the efficacy of AC treatment in MDS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals GLAD-PCR assay of R(5mC)GY sites in the regulatory region of tumor-suppressor genes associated with gastric cancer

Acta Naturae ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 124-133
Author(s):  
Boris S. Malyshev ◽  
Nina A. Netesova ◽  
Natalia A. Smetannikova ◽  
Murat A. Abdurashitov ◽  
Alexander G. Akishev ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Regulatory Region ◽  
Pcr Assay ◽  
Suppressor Genes ◽  
Regulatory Regions ◽  
Tissue Samples ◽  
Diagnostic Potential

At early stages of carcinogenesis, the regulatory regions of some tumor suppressor genes become aberrantly methylated at RCGY sites, which are substrates of DNA methyltransferase Dnmt3. Identification of aberrantly methylated sites in tumor DNA is considered to be the first step in the development of epigenetic PCR test systems for early diagnosis of cancer. Recently, we have developed a GLAD-PCR assay, a method for detecting the R(5mC)GY site in the genome position of interest even at significant excess of DNA molecules with a non-methylated RCGY site in this location. The aim of the present work is to use the GLAD-PCR assay to detect the aberrantly methylated R(5mC)GY sites in the regulatory regions of tumor suppressor genes (brinp1, bves, cacna2d3, cdh11, cpeb1, epha7, fgf2, galr1, gata4, hopx, hs3st2, irx1, lrrc3b, pcdh10, rprm, runx3, sfrp2, sox17, tcf21, tfpi2, wnt5a, zfp82, and znf331) in DNA samples obtained from gastric cancer (GC) tissues. The study of the DNA samples derived from 29 tumor and 25 normal gastric tissue samples demonstrated a high diagnostic potential of the selected RCGY sites in the regulatory regions of the irx1, cacna2d3, and epha7 genes; the total indices of sensitivity and specificity for GC detection being 96.6% and 100%, respectively.

Sign in / Sign up

Export Citation Format

Share Document