Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our previous study, we have found that leucine-rich repeats and immunoglobulin-like domains 1(LRIG1) can improve the chemosensitivity in U251 cells whereas the role of LRIG1 in multidrug resistance (MDR) remains unknown. Here, we reported that LRIG1 can reverse MDR by inhibiting epidermal growth factor (EGF) receptor (EGFR) and secondary inhibiting ATP-binding cassette, sub-family B member 1(ABCB1) and ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2). Our data showed that the expression of LRIG1 was significantly higher in O6-methylguanine DNA methyltransferase (MGMT) Promoter Methylation positive glioblastoma tissues compared to MGMT Promoter Methylation negative glioblastoma tissues. In addition, we found that LRIG1 expression was significantly decreased in MDR cells U251/TMZ compared to U251cells. Our results demonstrated that over-expression of LRIG1 can reverse the MDR. The expression of ABCB1 and ABCG2 were markedly suppressed when LRIG1 was over-expressed, supporting the negative relationship between LRIG1 level and ABCB1 and ABCG2 level in human specimen. Furthermore, we found that LRIG1 downregulated ABCB1 and ABCG2 through suppressing EGFR expression. In case of EGFR knockdown, the effect of LRIG1 on regulating MDR, ABCB1 and ABCG2 was partially compromised. Our results, for the first time, showed that LRIG1 can reverse MDR in glioblastoma, by negatively regulating EGFR and secondary suppressing the levels of ABCB1 and ABCG2.
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PMID:LRIG1, human EGFR inhibitor, reverses multidrug resistance through modulation of ABCB1 and ABCG2. 2580 Nov 20

Myocardial infarction (MI) is a major contributor to death and disability throughout the world. Increasing evidence shows that long noncoding RNAs (lncRNAs) are involved in the progression of MI. Here, we hypothesized that lncRNA potassium voltage-gated channel subfamily q member 1 overlapping transcript 1 (KCNQ1OT1) could affect the development of MI via regulation of Runt-related transcription factor (RUNX)3 by methylation. Initially, by ligation of the left anterior descending coronary artery, an acute MI (AMI) mouse model was established to collect the cardiac microvascular endothelial cells (CMECs), which revealed a high KCNQ1OT1 expression and a low RUNX3 expression with its high methylation. After that, KCNQ1OT1 knockdown or RUNX3 overexpression were transduced into the CMECs in order to detect their role in CMEC proliferation, apoptosis, and inflammatory response. Moreover, we assessed their interaction with the inflammatory Notch pathway, by determining the expression of Jagged 1, Hey1, Hes1, Notch intracellular domain, and Notch1. It was observed that after KCNQ1OT1 knockdown, the proliferation of AMI-CMECs was promoted, whereas their apoptosis was inhibited, accompanied by reduced level of inflammatory factors. These trends could also be achieved by RUNX3 overexpression via the Notch pathway. Finally, the regulation of DNA methyltransferase (DNMT)1-dependent methylation in RUNX3 by KCNQ1OT1 was determined, suggesting that KCNQ1OT1 could result in down-regulated RUNX3 expression through promoted RUNX3 methylation caused by recruiting DNMT1. Overall, this study demonstrates that KCNQ1OT1 silencing inhibits RUNX3 methylation, thereby offering protection against CMEC injury and inflammatory response in AMI, which may serve as a promising target for the disease treatment. -Wang, Y., Yang, X., Jiang, A., Wang, W., Li, J., Wen, J. Methylation-dependent transcriptional repression of RUNX3 by KCNQ1OT1 regulates mouse cardiac microvascular endothelial cell viability and inflammatory response following myocardial infarction.
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PMID:Methylation-dependent transcriptional repression of RUNX3 by KCNQ1OT1 regulates mouse cardiac microvascular endothelial cell viability and inflammatory response following myocardial infarction. 3162 14