Abstract 422: DNA hypermethylation or upregulated miRNA21 expression potentially leads to decreased mRNA expression of COL1A2, SFRP2, SOCS3, BCL2, MAL and PTGS2 in left-sided colorectal adenoma and cancer

2014 ◽  
Author(s):  
Bela Molnar ◽  
Balint Peterfia ◽  
Alexandra Kalmar ◽  
Peter Hollosi ◽  
Zsofia Brigitta Nagy ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Colorectal Adenoma ◽  
Dna Hypermethylation

scholarly journals DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Alexandra Kalmár ◽  
Bálint Péterfia ◽  
Péter Hollósi ◽  
Orsolya Galamb ◽  
Sándor Spisák ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Colorectal Adenoma ◽  
Dna Hypermethylation

scholarly journals Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bokyung Ahn ◽  
Yang Seok Chae ◽  
Soo Kyung Lee ◽  
Moa Kim ◽  
Hyeon Soo Kim ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Lines ◽  
Adenylate Kinase ◽  
Dna Methyltransferase ◽  
Colorectal Adenocarcinoma ◽  
Adenine Nucleotides ◽  
Inverse Correlation ◽  
Dna Hypermethylation ◽  
Normal Tissues ◽  
The Difference

AbstractAdenylate kinase 5 (AK5) belongs to the adenylate kinase family that catalyses reversible phosphate transfer between adenine nucleotides, and it is related to various energetic signalling mechanisms. However, the role of AK5 in colorectal cancer (CRC) has not been reported. In this study, AK5 was significantly hypermethylated in CRC compared to adjacent normal tissues (P < 0.0001) and normal tissues (P = 0.0015). Although the difference in mRNA expression was not statistically significant in all of them, the selected 49 cases of CRC tissues with AK5 hypermethylation with the cut off value of 40% showed a significant inverse correlation with mRNA expression (P = 0.0003). DNA methylation of AK5 promoter significantly decreased and AK5 expression recovered by 5-aza-2′-deoxycytidine, DNA methyltransferase inhibitor in CRC cell lines. In addition, AK5 promoter activity significantly decreased due to DNA methyltransferase, and it increased due to 5-aza. Moreover, AK5 regulated the phosphorylated AMPK and mTOR phosphorylation and inhibited the cell migration and cell invasion in CRC cell lines. Furthermore, low AK5 expression is associated with poor differentiation (P = 0.014). These results demonstrate that the AK5 promoter is frequently hypermethylated and induced methylation-mediated gene down-regulation. AK5 expression regulates AMPK/mTOR signalling and may be closely related to metastasis in colorectal adenocarcinoma.

Frequent Epigenetic Inactivation of MSX2 In Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4645-4645 ◽  
Author(s):  
Chen Zhao ◽  
Xin Han ◽  
Yu H. Zhang ◽  
Xiaoyan Huang ◽  
Aili Dai ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Functional Role ◽  
Methylation Status ◽  
Dna Hypermethylation ◽  
Expression Levels ◽  
Mrna Expression Levels ◽  
Acute Myeloid

Abstract Abstract 4645 DNA hypermethylation has been implicated in the tumorigenesis and prognosis in acute myeloid leukemia (AML). To identify and validate relevant methylated genes in AML, we have compared expression levels and methylation status of 26 candidate genes. One of the interesting candidates identified in our study is MSX2. MSX2 is a member of muscle segment homeobox gene family. MSX2 plays a role in promoting cell growth under certain conditions and may be an important target for RAS signaling pathways. However, the mechanism of transcriptional regulation and functional role of MSX2 in hematological malignancies, especially AML, are poorly understood. In our study, we determined the methylation status, and analyzed the expression levels of MSX2 in AML cell lines and primary AML cells using RT-PCR and/or Taqman real-time PCR. MSX2 mRNA expression was robust in the normal granulocytes and blasts of human bone-marrow, but was either absent or significantly diminished in 6 of 9 (66.7%) AML cell lines. The expression levels of MSX2 in those 6 AML cell lines were restored after treatment of 5-aza 2′-deoxycytidine. In addition, COBRA (Combined Bisulfite Restriction) analysis demonstrated hypermethylation of MSX2 in those AML cell lines (6 of 9, 66.7%), and partial methylation in 3 of 9 AML cell lines. The methylation status was inversely correlated with the mRNA expression levels of MSX2 in those cell lines. Furthermore, the expression levels and methylation status of MSX2 in human primary AML cells were evaluated. COBRA analysis demonstrated frequent hypermethylation of MSX2 in primary AML patient samples (19 of 32, 59.3%). Importantly, the mRNA expression levels of MSX2 as shown by Taqman real-time PCR in those 19 primary AML patient samples were inversely correlated with the methylation status of MSX2. These findings confirmed the role of frequent DNA hypermethylation in silencing MSX2 in AML. We are in the process of determining the functional role of MSX2 in the pathogenesis of AML. In addition, diagnostic and prognostic values of MSX2 in AML are being pursued. Disclosures: No relevant conflicts of interest to declare.

scholarly journals DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression

2011 ◽  
Vol 13 (3) ◽  
pp. 280-289 ◽  
Author(s):  
Shichun Zheng ◽  
E. Andres Houseman ◽  
Zachary Morrison ◽  
Margaret R. Wrensch ◽  
Joseph S. Patoka ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Dna Hypermethylation

Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence

2019 ◽  
Vol 57 (8) ◽  
pp. 1251-1260 ◽  
Author(s):  
Georgia Papachristopoulou ◽  
Apostolos Malachias ◽  
Marina Devetzi ◽  
Evdoxia Kamouza ◽  
Andreas Scorilas ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Colorectal Adenoma ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Colorectal Adenomas ◽  
Normal Colonic Mucosa ◽  
Endocrine Tumors ◽  
Advanced Tumor Stage ◽  
Positive Expression ◽  
Advanced Tumor

Abstract Background Kallikrein-related peptidases (KLKs) are a subgroup of serine proteases located on chromosome 19q13.3. Most KLKs have been extensively studied as potential biomarkers for several carcinomas and other diseases. KLK5 was originally identified from a keratinocyte library, and its enzyme was purified from the stratum corneum of human skin. KLK5 was shown to be differentially expressed in a variety of endocrine tumors, although it is not as yet examined widely in colorectal cancer (CRC). Methods In this study, we quantitatively assessed the mRNA expression status of KLK5 in 197 colorectal tissues from 133 patients (70 cancerous and their paired normal colonic mucosa for 64 of them, as well as 63 colorectal adenomas) by quantitative real-time PCR (qPCR) using TaqMan probes. Statistical analysis evaluated the results. Results It was shown that KLK5 expression is reduced following the histologically non-cancerous-adenoma sequence (p<0.001), whereas it is increased during the sequence adenoma-carcinoma (p<0.001). Furthermore, KLK5 positive expression is associated with positive nodal status (p=0.022), advanced tumor stage (p=0.038) and high histological grade (p=0.033). Cox univariate analysis revealed that KLK5 positive expression is associated with disease-free survival (DFS) (p=0.028) and overall survival (OS) of patients (p=0.048). Kaplan-Meyer survival models showed that patients with positive KLK5 expression have lower DFS (p=0.009) and OS (p=0.019). Receiver operating characteristic (ROC) analysis demonstrated for first time that KLK5 expression had significant discriminatory values between cancer and adenoma tissues (area under the curve [AUC] 0.77; 95% confidence interval [CI]=0.69–0.85, p=0.03). Conclusions KLK5 mRNA expression may be useful for the differentiation of CRC from colorectal adenoma and represents a potential unfavorable prognostic biomarker for CRC.

RAP1GAP Functions as a Tumor Suppressor Gene and Is Regulated by DNA Methylation in Differentiated Thyroid Cancer

2021 ◽  
Vol 161 (5) ◽  
pp. 227-235
Author(s):  
Bita Faam ◽  
Mohammad A. Ghaffari ◽  
Layasadat Khorsandi ◽  
Ata A. Ghadiri ◽  
Mehdi Totonchi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Mrna Expression ◽  
Protein Level ◽  
Differentiated Thyroid Cancer ◽  
Regulatory Region ◽  
Dna Hypermethylation ◽  
Tumor Stages ◽  
Methylation Patterns

Inactivation of tumor suppressor genes, such as <i>RAP1GAP</i>, by hypermethylation of their regulatory region can give rise to thyroid tumors. The aim of this study was to investigate the expression of the <i>RAP1GAP</i> gene and the DNA methylation patterns of its CpG74<sub>a</sub>, CpG74<sub>b</sub>, and CpG24 in an Iranian population with differentiated thyroid cancer (DTC). In this study, 160 individuals who underwent thyroidectomy in the Tehran Erfan Hospital between 2018 and 2020 were selected. DNA methylation patterns of selected CpG islands (CpG74<sub>a</sub>, CpG74<sub>b</sub>, and CpG24) were determined using methylation-specific PCR. The mRNA expression and protein level of ­RAP1GAP were also evaluated. SW1736 and B-CPAP cells were treated with 5-aza-2′-deoxycytidine (5-Aza) to demethylate these regions. The hypermethylation rates of CpG74<sub>a</sub> and CpG24 in DTC samples were significantly higher than in the control. The mRNA expression and protein level of ­RAP1GAP were significantly decreased in the DTC group. In the DTC group, hypermethylation in CpG74<sub>a</sub> was correlated with decreasing <i>RAP1GAP</i> expression (<i>R</i><sup>2</sup>: 0.34; <i>p</i> = 0.043). CpG74<sub>a</sub> with a specificity of 86.4% has significant prediction power to distinguish between DTC and normal thyroid tissues. Additionally, hypermethylation of CpG74<sub>a</sub> was significantly associated with higher tumor stages (stage III-IV: 77%; stage I-II: 23%; <i>p</i> = 0.012). Increasing expression of <i>RAP1GAP</i> after demethylation with 15 µM of 5-Aza was observed in both cell lines. These results indicate that DNA hypermethylation in CpG74<sub>a</sub> can be considered as an epigenetic biomarker in DTC.

scholarly journals Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene

2019 ◽  
Vol 59 (6) ◽  
pp. 2497-2506 ◽  
Author(s):  
Rihua Cong ◽  
Xiaoli Qu ◽  
Hui Zhang ◽  
Yongling Hu ◽  
Silin Ye ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Growth Hormone Receptor ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Transcriptional Level ◽  
Dna Hypermethylation ◽  
Growth Axis ◽  
Weaning Piglets ◽  
Igfbp 3

Abstract Purpose The aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring. Methods Fourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n = 7) diet or a high-protein (HP, 150% of SP, n = 7) diet during pregnancy. Offspring (one male and one female per group, n = 14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples were analyzed for Tch, insulin and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Liver samples were analyzed for IGFBP-3 and IGF-I mRNA expression by qRT-PCR and for IGFBP-3, IGF1R and growth hormone receptor (GHR) protein expression by Western blotting. The underlying mechanism of IGFBP-3 regulation was determined by methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). Results High-protein exposure resulted in significantly higher body and liver weights of piglets, and it increased their serum T3 and T4 levels at birth and/or at weaning. Furthermore, the IGFBP-3 protein content in the liver and serum was significantly reduced in the HP-exposed weaning piglets, whereas at the transcriptional level IGFBP-3 mRNA expression was downregulated in the livers of HP group piglets. Finally, DNA hypermethylation and higher enrichment of the histone repressive marks H3K27me3 and H3K9me3 were observed. Conclusions Taken together, these results suggest that a maternal high-protein diet during gestation epigenetically reprograms IGFBP-3 gene expression to modulate the hepatic growth axis in weaning piglets.

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