Chromosome 16q Located Genes CDH1, CDH13 and ADAMTS18 Are Correlated and Frequently Methylated But Not Associated With DNMTs levels In Human Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4289-4289
Author(s):  
Lobna A Alkebsi ◽  
Hiroshi Handa ◽  
Kenichi Tahara ◽  
Hiroaki Shimizu ◽  
Takuma Ishizaki ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tumor Suppressor Genes ◽  
Significant Positive Correlation ◽  
Methylation Status ◽  
Promoter Hypermethylation ◽  
Expression Levels ◽  
Significant Difference ◽  
Human Lymphoma ◽  
Chromosome 16Q ◽  
Mrna Expression Levels

Abstract Hypermethylation of promoter contributes to the transcriptional repression of a number of cancer associated genes. In lymphoma, the promoter hypermethylation of many tumor suppressor genes (TSGs), such as p16, has been already known. Using methylation-specific PCR (MSP) and quantitative real-time PCR (qRT-PCR), we examined promoter methylation status and mRNA expression levels of E-cadherin (CDH1), H-cadherin (CDH13) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS18) which are putative TSGs located on chromosome 16q, and also examined the mRNA expression levels of DNA methyltransferases (DNMT1, 3A and 3B) and studied the correlation between these different tested parameters in 36 of lymphomas [included 29 diffuse large B cell (DLBCL) and seven mantle cell lymphoma (MCL)] and 16 non-malignant lymphoid tissues after obtaining informed consent. The expression of DNMTs mRNA were significantly higher in lymphomas compared to non-malignant tissues (p<0.05). Promoter hypermethylation of CDH1, CDH13, and ADAMTS18 was detected in 31/36 (86%), 33/36 (91.6%) and 28/36 (77.7%) of lymphoma, respectively. The expression of CDH1 and ADAMTS18 was significantly reduced in the patients with hypermethylated promoter when compared to unmethylated (p<0.01 and p<0.05, respectively), while no significant difference was found in CDH13. CDH1 and ADAMTS18 expressions were significantly reduced in lymphomas compared to non-malignant tissues (p<0.01), while CDH13 showed no significant difference. Notably, there was significant positive correlation between the expression levels of CDH1 and CDH13 (r = 0.735, p<0.01) (Fig. 1A). Moreover, ADAMTS18 expression showed significant positive correlation with both CDH1 and CDH13 expression levels (r = 0.625, p<0.01; r = 0.720, p<0.01, respectively) (Fig. 1B, C). Also there was significant negative correlation between the expression levels of DNMT3A and 3B with ADAMTS18 (r = -0.396, p<0.01; r = -0.364, p<0.01, respectively), but not with CDH1 and CDH13 (Fig. 2A and B). We could not find any correlation between the levels of DNMTs mRNA and the methylation status of CDH1, CDH13 and ADAMTS18. We examined the effect of 5-Aza-2-deoxycytidine (5-aza-dC) treatment on CDH1, CDH13 and ADAMTS18 expression levels and their methylated promoters in 3 of lymphoma cell lines (Raji, CTB-1 and SLVL) and one patient primary DLBCL cell line. We found that 5-aza-dC treatment of CDH1, CDH13 and ADAMTS18-methylated cell lines led to restoration of their expression levels (Fig. 3A, B, and C). Our results showed that CDH1, CDH13 and ADAMTS18, tumor suppressor genes adjacently located at chromosome 16q, are remarkably correlated and frequently methylated in human lymphoma and their methylation could not be explained solely by the expression level of DNMTs mRNA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evaluating macrophage migration inhibitory factor 1 expression as a prognostic biomarker in colon cancer

Tumor Biology ◽  
2020 ◽  
Vol 42 (6) ◽  
pp. 101042832092452
Author(s):  
Lina Olsson ◽  
Gudrun Lindmark ◽  
Marie-Louise Hammarström ◽  
Sten Hammarström ◽  
Basel Sitohy
Keyword(s):  
Colon Cancer ◽  
Lymph Nodes ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Expression Levels ◽  
Significant Difference ◽  
Mrna Expression Levels ◽  
Inhibitory Factor 1

Objective: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker. Methods: Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I–IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase–polymerase chain reaction. Expression of migration inhibitory factor 1 protein was investigated by two-color immunohistochemistry and immunomorphometry. Results: Migration inhibitory factor 1 mRNA was expressed at 60 times higher levels in primary colon cancer tumors compared to normal colonic tissue (medians 8.2 and 0.2 mRNA copies/18S rRNA unit; p < .0001). A highly significant difference in mRNA expression levels was found between hematoxylin-eosin positive lymph nodes and hematoxylin-eosin negative lymph nodes (p < .0001). Migration inhibitory factor 1 and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer-tumor cells. Kaplan–Meier survival model and hazard ratio analysis, using a cutoff level at 2.19 mRNA copies/18S rRNA unit, revealed that patients with lymph nodes expressing high levels of migration inhibitory factor 1 mRNA had a 3.5-fold (p = .04) higher risk for recurrence, associated with a small, but significant, difference in mean survival time (7 months, p = .03) at 12 years of follow-up. Conclusion: Although migration inhibitory factor 1 mRNA expression levels were related to severity of disease and lymph node analysis revealed that colon cancer patients with high levels had a shorter survival time after surgery than those with low levels, the difference was small and probably not useful in clinical practice.

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.

Differences in Expression Patterns of DNMTs and TSG Proteins in Lymphoid Tissue Section Play an Important Role in Their Association

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2657-2657
Author(s):  
Lobna Alkebsi ◽  
Hiroshi Handa ◽  
Kenichi Tahara ◽  
Hiroaki Shimizu ◽  
Takuma Ishizaki ◽  
...  
Keyword(s):  
B Cells ◽  
Protein Expression ◽  
Mrna Expression ◽  
Lymphoid Tissue ◽  
Methylation Status ◽  
Lymphoid Tissues ◽  
Expression Levels ◽  
Protein Expressions ◽  
Mrna Expression Levels ◽  
E Cadherin

Abstract In situ, patterns of expression of DNMTs (DNA methytransferases) in normal reactive tonsillar tissue have been examined. Difference in pattering of expression of DNMTs and TSG (Tumor suppressor genes) proteins in lymphoid tissue section is an important question in relation to their association with each other as well as relationship to mRNA gene expression level. In order to examine this issue, we examined DNMTs and TSG proteins expression by immunohistochemistry in sections of paraffin-embedded specimens obtained from 33 subjects of lymphoma and 16 subjects of Non-malignant tissues after receiving written informed consent. The specimens were stained with anti-DNMTs (DNMT1, DNMT3A and DNMT3B) and anti-TSG (E-cadherin, H-cadherin and ADAMTS18) antibodies. In addition, using fresh-frozen optimal cutting temperature (OCT) compound-embedded tissue specimens before any treatment, we examined mRNA expression levels and promoter methylation status of E-cadherin (CDH1), H-cadherin (CDH13) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS18) using quantitative real-time PCR (qRT-PCR) and methylation-specific PCR (MSP), respectively. The expression of nuclear DNMTs proteins (DNMT1 and 3A) in lymphoma section was observed in [17/33 (51%); 27/33 (81%)], whereas in non-malignant tissues was [14/16 (87.5%); 13/16 (81%)], respectively. The DNMT3B protein expression was not detected in our tissue samples, which might be explained by the fact that DNMT3B characterized by alternative splicing as shown previously. Membrane proteins (E-cadherin, H-cadherin and ADAMTS18) showed low expression [12/33 (36%); 10/33 (30%); 6/33 (18%), respectively], when compared to non-malignant tissue sections [12/16 (75%); 7/16 (43%); 8/16 (50%), respectively]. The expression levels of CDH1, CDH13 and ADAMTS18 mRNAs were non-significantly reduced in their corresponding protein negative expression compared to the levels in cases with positive protein expression (p =0.112, p =0.378, p =0.077, respectively). We could not find any correlation between mRNA/protein expression levels of DNMTs and the methylation status of CDH1, CDH13 and ADAMTS18. Importantly, by immunostaining especially in non-malignant lymphoid tissues, we found that DNMT1 was highly detected in germinal center B cells (GC B cells) with gradual decrease or no expression in the mantle, marginal, interfollicular and T cells zones. Whereas DNMT3A was preferentially and scattered like expressed in the cells of the surrounding zones out of the germinal centers. Furthermore, E-cadherin, H-cadherin and ADAMTS18 proteins expression were detected on the cell surface membrane of the cells outside the GC but at rates somehow more than those cells inside the GC (Fig. 1). This is supported by the significant association observed between the frequency of DNMT3A with both E-cadherin and ADAMTS18, protein expressions (Chi square: p <0.05), while no association with H-cadherin protein expression. In addition, DNMT1 protein expression did not show significant association with the protein expressions of E-cadherin, H-cadherin and ADAMTS18. Moreover, the mRNA expression levels of DNMT3A and 3B showed high significant levels (p <0.05) in cases with negative protein expressions of both E-cadherin and ADAMTS18 when compared to cases with positive protein expressions (Fig. 2A and C). The DNMT1 mRNA expression level did not show any significant difference between the negative and positive protein expressions of E-cadherin, H-cadherin and ADAMTS18 (Fig. 2B). Furthermore, there was no significant association between the mRNA levels of DNMTs and H-cadherin protein expression. Expression of H-cadherin protein was frequently observed in the endothelial venules and trabeculae of the lymphoid tissues (Fig. 1) which might cause of its lack of association with both DNMT1 and DNMT3A. In conclusion, these results indicate that as a result of differences in pattering of DNMTs and TSG protein expressions detected in lymphoid tissues by immunohistochemistry staining, it might be one of the reasons of the association with each other and their mRNA expression levels across the spectrum of lymphomas and non-malignant lymphoid tissues. Disclosures No relevant conflicts of interest to declare.

ERCC1 expression as a predictor for chemosensitivity in recurrent colorectal cancer patients receiving cisplatinum (CDDP) plus S-1 chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13065-13065
Author(s):  
K. Uchida ◽  
K. Hayashi ◽  
H. Kuramochi ◽  
K. Kudo ◽  
S. Miyakura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Recurrent Colorectal Cancer ◽  
Internal Reference ◽  
Expression Levels ◽  
Significant Difference ◽  
Mrna Gene ◽  
Ercc1 Expression ◽  
Colorectal Cancer Patients ◽  
Mrna Expression Levels

13065 Background: To test the hypotheses of whether the relative mRNA expression of excision cross complement-1 (ERCCI) are associated with response to CDDP+S-1 chemotherapy in recurrent colorectal cancer (CRC). We assessed the relationship between ERCC1 mRNA expression levels and the response. Methods: Thirty four patients with relapsed CRC were treated with cisplatin 30 mg/m2 on Day 1 and Day 8, and S-1 twice daily (BSA = 1.5 m2, 60 mg/day) for 21 days, followed by a 2-week period of no treatment. cDNA was derived from paraffin-embeded tumor specimens to determine ERCC1 mRNA expression relative to the internal reference gene beta-actin using fluorescence-based, real-time reverse transcriptase polymerase chain reaction (Taqman) system. Results: Among 34 CRC patients, 4 patients were evaluated as CR, 13 as PR, and 17 as NC/PD. Relative ERCC1 mRNA gene expression level showed significant difference by the response with median expression levels of 0.70/1.33/1.80 in CR/PR/NC+PD patients respectively (P = 0.04). Conclusions: These data suggest that intratumoral ERCC1 mRNA expression levels are independent predictive markers of response to CDDP+S-1 chemotherapy in colorectal cancer. No significant financial relationships to disclose.

scholarly journals Survivin and Vegf as Novel Biomarkers in Diagnosis of Endometriosis/ Survivin i vegf kao novi biomarkeri u dijagnostici endometrioze

2016 ◽  
Vol 35 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Milena Acimovic ◽  
Snezana Vidakovic ◽  
Natasa Milic ◽  
Katarina Jeremic ◽  
Milos Markovic ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Peripheral Blood ◽  
Transvaginal Ultrasound ◽  
False Negative ◽  
Diagnostic Tools ◽  
Expression Levels ◽  
Diagnostic Score ◽  
Significant Difference ◽  
Serum Ca125 ◽  
Mrna Expression Levels

Summary Background: The aim of this study was to investigate the role of peripheral blood markers as additional diagnostic tools to transvaginal ultrasound (TVU) findings in the diagnosis of endometriosis. Methods: This study included 40 patients undergoing laparoscopy for suspected endometriosis from January to December 2012. Preoperative levels of serum CA125, CA19-9, CEA and mRNA expression levels for survivin and VEGF were obtained. Real-time PCR was used to determine relative gene expression. A new diagnostic score was obtained by deploying the peripheral blood markers to the TVU findings. Statistical methods used were Chi-square, Fisher’s, Student’s t-test or the Mann - Whitney test. Results: There was a statistically significant difference in serum CA125, survivin and VEGF levels in patients with endometriosis and those without endometriosis (p<0.001, p=0.025 and p=0.009, respectively). False negative TVU findings were noted in 3/13 patients (23.1%) with peritoneal endometriosis without ovaries involvement. High sensitivity (93.3%), specificity (90.0%), PPV (96.6%), NPV (81.8%) and accuracy (92.5%) were obtained for a diagnostic score based on TVU and significant peripheral blood markers (CA125, survivin and VEGF). Conclusions: Determination of serum CA125, mRNA expression levels for survivin and VEGF along with TVU can contribute to higher accuracy of the noninvasive diagnostic tools for endometriosis.

2′-Deoxy-5-Azacytidine Enhances Cytotoxic Effect Of Other Anti-Leukemic Agents Synergistically In Acute Lymphoblastic Leukemia Cell Line

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5564-5564
Author(s):  
Kimiyoshi Sakaguchi ◽  
Hiroyoshi Takahashi
Keyword(s):  
Mrna Expression ◽  
Mtt Assay ◽  
Research Funding ◽  
Caspase 3 ◽  
Lymphoblastic Leukemia ◽  
Methylation Status ◽  
Expression Levels ◽  
Apoptotic Genes ◽  
Mrna Expression Levels

Abstract Introduction Advances in chemotherapy have improved the outcome of childhood acute lymphoblastic leukemia (ALL). However, leukemia cells in refractory ALL are often resistant to anti-leukemic agents. Although recent studies have focused on the epigenetic changes in refractory leukemia, the relationship between the demethylating agent 2′-deoxy-5-azacytidine (decitabine, DAC) and ALL remains unclear. Here, we examine the combined effects of DAC and anti-leukemic agents such as clofarabine (CLO) and etoposide (ETO) on the ALL cell line CCRF-CEM. Methods and results In vitro drug sensitivity was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. We cultured CCRF-CEM cells for 72 hours with or without DAC, and then removed DAC (when present) prior to culturing CCRF-CEM cells for 48 hours with ETO or CLO, or without chemotherapeutic drugs. After culturing for 48 hours, we removed the chemotherapeutic drugs and measured in vitro drug sensitivity using MTT assay. The MTT assay was performed in triplicate. We then evaluated the inhibitory concentration at 50% (IC50). IC50 for ETO, ETO+DAC, CLO, and CLO+DAC was 3.36, 0.625, 4.96, and 1.92, respectively. The combination Index (CI) was produced with Calcusyn® software, which uses the methodology of Chou and Talalay to perform formal synergy analyses. A CI < 1 indicated a synergistic effect. The CI was 0.026 for ETO+DAC and 0.431 for CLO+DAC. We assayed with Annexin-V, PI staining, and caspase-3/7 to detect apoptosis. We observed apoptosis rates of 31.6%, 53.3%, 31.2%, and 52.6% for ETO, ETO+DAC, CLO, and CLO+DAC, respectively. We observed greater caspase-3/7 activity with DAC+CLO and DAC+ETO than with CLO and ETO. Using real-time reverse transcription polymerase chain reaction (RT-qPCR) in CCRF-CEM cells, we examined mRNA expression levels for the pro-apoptotic genes BAK, BID, BAX, BAD, BIM, PUMA, ATM, TP53, and NOXA, as well as those for the anti-apoptotic genes BCL2, BCL2L1, and XIAP. The expression level of each target gene was calculated by normalizing it to the housekeeping gene GAPDH. The RT-qPCR was performed in triplicate. We used Student’s t test to compare the data. We observed DAC increased mRNA expression levels of BAX and NOXA, but decreased those for BAK, BID, PUMA, BCL2L1, ATM, TP53, and XIAP. We then analyzed the methylation status of pro- and anti-apoptotic genes after 48 hours incubation with or without DAC. Methylation status of BAK, NOXA, BCL2L1 and XIAP incubation with DAC was 1.3%, 3.3%, 2.5% and 72.9%, respectively. Methylation status of BAK, NOXA, BCL2L1 and XIAP incubation without DAC was 1.9%, 3.6%, 0.7% and 92.3%, respectively. There was no significant difference. Discussion Our results showed that DAC synergistically enhances CLO and ETO cytotoxicity, and this cytotoxic effect depends on caspase-3/7 activity. We examined mRNA expression levels of pro- and anti-apoptotic genes. We hypothesized that DAC would increase mRNA expression levels of most pro-apoptotic genes, and decrease mRNA levels of most anti-apoptotic genes. We found that DAC decreased some pro-apoptotic genes, such as BAK, BID, PUMA, ATM, and TP53, which disproves our hypothesis. Our present findings are similar to those of Shin et al., who reported that DAC decreased BID mRNA expression levels. However, they provided no explanation for this activity. Our results show that DAC did not demethylate the CpG of BAK, NOXA, BCL2L1, or XIAP. Thus, DAC must demethylate the CpG of other genes. Nevertheless, many genes are involved in apoptosis, and it remains unclear which genes are demethylated by DAC. Disclosures: Sakaguchi: Yakult Honsha Company: Research Funding; Japan Leukemia Research Fund: Research Funding; Japan Society for the Promotion of Science: Research Funding; Sanofi: Research Funding; Teijin Pharma: Research Funding.

Imprinting in the schizophrenia candidate gene GABRB2

2011 ◽  
Vol 26 (S2) ◽  
pp. 823-823
Author(s):  
F. Pun ◽  
C. Zhao ◽  
W. Lo ◽  
S. Ng ◽  
S. Tsang ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Mrna Expression ◽  
Association Studies ◽  
Methylation Status ◽  
Dependent Manner ◽  
Expression Levels ◽  
Allele Specific ◽  
Parent Of Origin ◽  
Allele Specific Methylation ◽  
Mrna Expression Levels

Imprinting, characterized by unequal expression of the offspring's genes in a parent-of-origin dependent manner, has been functionally implicated in brain development and in psychiatric disorders. In this study, unambiguous distortion in paternal but not maternal transmission of the disease-associated single-nucleotide polymorphism (SNP) rs6556547 (T/G) clearly indicated the presence of parent-of-origin effect (POE) in the GABAA receptor β2 subunit gene (GABRB2). ‘Flipping’ of allelic mRNA expression in heterozygotes of SNP rs2229944 (C/T) and the observed two-tiered distribution of mRNA expression levels in heterozygotes of the disease-associated SNP rs1816071 (G/A) furnished important support for the occurrence of imprinting at GABRB2. Imprinting in effect introduced heterozygotes from different parents-of-origin endowed with dissimilar mRNA expression capabilities. The deficit of upper-tiered expressions accounted for the lowered mRNA expression levels in the schizophrenic heterozygotes. This pointed to the necessity of differentiating between two kinds of heterozygotes of different parental origins in disease association studies on GABRB2. Bisulfite sequencing revealed hypermethylation in the neighborhood of SNP rs1816071, and methylation differences between controls and schizophrenia patients. Notably, allele-specific methylation was observed at the disease-associated SNPs rs6556547 and rs1816071. These findings raised the possibility that CpG methylation status of these sites could have an impact on the expression of GABRB2 and the risk of schizophrenia. Furthermore, the occurrence of imprinting and allele-specific methylation in the schizophrenia candidate gene GABRB2 was compatible with the epigenetic hypothesis for schizophrenia pathophysiology, thereby calling for the need to explore the role of epigenetic factors in mediating susceptibility to schizophrenia.

scholarly journals Blood CDKN2A Gene Expression in Aging and Neurodegenerative Diseases

2021 ◽  
pp. 1-8
Author(s):  
Hiroaki Mori ◽  
Yu Funahashi ◽  
Yuta Yoshino ◽  
Hiroshi Kumon ◽  
Yuki Ozaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neurodegenerative Diseases ◽  
Mrna Expression ◽  
Kinase Inhibitor ◽  
Methylation Status ◽  
Healthy Controls ◽  
Expression Levels ◽  
Cdkn2a Gene ◽  
Potential Biomarker ◽  
Mrna Expression Levels

Background: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important gene in cellular senescence and aging. Objective: This study assessed the utility of blood CDKN2A mRNA expression levels and methylation status as a potential biomarker for aging and the pathogenesis of Alzheimer’s disease (AD). Methods: The correlation between CDKN2A mRNA expression levels and age was examined in 45 healthy subjects, after which mRNA expression levels were compared among 46 AD patients, 20 mild cognitive impairment due to AD patients, 21 Parkinson’s disease patients, 21 dementia with Lewy bodies patients, and 55 older healthy controls. The methylation rates of the second exon of the CDKN2A gene, known to influence its expression levels, was also examined. Results: A significant correlation between CDKN2A mRNA expression levels and age was found (Spearman’s rank correlation coefficient: r = 0.407, p = 0.005). CDKN2A mRNA expression levels in blood were significantly decreased in AD patients, although those of healthy controls were significantly increased with age. Further, only in AD patients were CDKN2A mRNA expression levels significantly and positively correlated with methylation rates. Conclusion: Although further research with a larger sample size is needed to elucidate the relationships between CDKN2A gene expression in blood and the development of other neurodegenerative diseases, CDKN2A mRNA expression in blood may be a biomarker for differentiating AD from normal aging and other neurodegenerative diseases.

scholarly journals The effect of genistein on lipid levels and LDLR, LXRα and ABCG1 expression in postmenopausal women with hyperlipidemia

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Zhang ◽  
Xiao-Xing Chi
Keyword(s):  
Mrna Expression ◽  
Postmenopausal Women ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Expression Levels ◽  
Significant Difference ◽  
Mrna Expression Levels

Abstract Background This study investigates the effect of genistein (Gen) on the lipid profiles and expression of low-density lipoprotein receptor (LDLR), liver X receptor α (LXRα) and ATP-binding cassette transporter G1 (ABCG1) in the plasma macrophages of postmenopausal women with hyperlipidemia in China. Methods This study considered 187 cases, where 160 postmenopausal women had hyperlipidemia. The subjects were divided into placebo group (PG) and experimental group (EG). EG received 60 mg/day of Gen, PG received placebo for 6 months. Body weight, height, waist circumference, body mass index and glucose levels were determined according to standard operating procedures. The triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein-A1 (Apo-A1) and apolipoprotein-B (Apo-B) levels were detected in the plasma macrophages using ELISA. The protein and mRNA expression levels of LDLR, LXRα and ABCG1 were detected by western blot and real-time PCR techniques, respectively. Results Compared to the baseline, Gen effectively lowered TG, TC and LDL-C levels, whereas HDL-C levels as well as the protein and mRNA expression levels of LDLR, LXRα and ABCG1 (p < 0.05) were increased. There was a significant difference in the expression of LDLR protein between the two groups (p < 0.05). The mRNA expression levels of LDLR, LXRα and ABCG1 were significantly increased in the EG compared to the PG. Conclusion Gen effectively modulated the plasma lipid indices. The cholesterol-lowering effects of Gen may be attributed to its regulation on some of the key genes involved in cholesterol homeostasis.

Sign in / Sign up

Export Citation Format

Share Document