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Methylation

TCF3 is epigenetically silenced by EZH2 and DNMT3B and functions as a tumor suppressor in endometrial cancer

2 | Jul 28 2021

Tao Gui et al. found that TCF3 functions as a tumor suppressor epigenetically silenced by EZH2 and DNMT3B in EC. [Read the Full Post]

CDKN2A Determines Mesothelioma Cell Fate to EZH2 Inhibition

3 | Jul 22 2021

Giulia Pinton et al. found that the expression of CDKN2A predicted cell fate in response to EZH2 inhibition and could potentially stratify tumors likely to undergo apoptosis. [Read the Full Post]

The bromodomain inhibitor JQ1+ reduces calcium-sensing receptor activity in pituitary cell-lines

6 | Jul 06 2021

Kate E Lines et al. thought that reducing CaSR expression might be a viable option in the treatment of pituitary tumours. [Read the Full Post]

SMALL MOLECULE IMAGING AGENT FOR MUTANT KRAS G12C

13 | May 19 2021

Peter D Koch et al. found that two fluorescent derivatives (BODIPY FL and BODIPY TMR) of ARS-1323 bind mutant KRAS and could be used for biochemical binding screens. [Read the Full Post]

MLL1 combined with GSK3 and MAP2K inhibition improves the development of in vitro-fertilized embryos

14 | Apr 27 2021

Xuejie Han et al. found that the application of 3i provided a new method for improving IVF embryo production in domestic animals. [Read the Full Post]

H3K36 methylation reprograms gene expression to drive early gametocyte development in Plasmodium falciparum

15 | Apr 25 2021

Jessica Connacher et al. found that H3K36me2&3-associated repression of genes was therefore involved in key transcriptional shifts that accompanied the transition from early gametocyte differentiation to intermediate development. [Read the Full Post]

A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets

14 | Apr 11 2021

Juan Bayo et al. found that mutations and changes in expression of epigenetic modifiers were common events in human hepatocellular carcinoma, leading to an aggressive gene expression program and poor clinical prognosis. [Read the Full Post]

Dissecting the Role of BET Bromodomain Proteins BRD2 and BRD4 in Human NK Cell Function

15 | Apr 10 2021

Adam P Cribbs et al. found that compelling argument for further clinical investigation. [Read the Full Post]

Oxidative stress abrogates the degradation of KMT2D to promote degeneration in nucleus pulposus

18 | Mar 23 2021

Wenbin Xu et al. approved that oxidative stress induced ROS production promote the process of NP degeneration by enhancing KMT2D mediated transcriptional regulation of matrix degeneration related genes during NP degeneration. [Read the Full Post]

Rational Design, synthesis and biological evaluation of novel triazole derivatives as potent and selective PRMT5 inhibitors with antitumor activity

19 | Mar 21 2021

Kongkai Zhu et al. described the design, synthesis and biological evaluation of a series of novel, potent and selective PRMT5 inhibitors with antiproliferative activity against Z-138 mantle cell lymphoma cell line. [Read the Full Post]

EPZ015666, a selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an antitumour effect in retinoblastoma

32 | Jan 29 2021

Xing Liu et al. found that EPZ015666 inhibited retinoblastoma cell proliferation and led to cell cycle arrest at the G1 phase. [Read the Full Post]

Inhibition of PRMT5 Attenuates Oxidative Stress-Induced Pyroptosis via Activation of the Nrf2/HO-1 Signal Pathway in a Mouse Model of Renal Ischemia-Reperfusion Injury

35 | Jan 29 2021

Changhui Diao et al. thought that PRMT5 might be a promising therapeutic target. [Read the Full Post]

Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer

32 | Jan 17 2021

R Vatapalli et al. thought that DOT1L selectively regulated the tumorigenicity of AR-positive prostate cancer cells and was a promising therapeutic target for PCa. [Read the Full Post]

Targeting LSD1 for acute myeloid leukemia (AML) treatment

34 | Jan 14 2021

Shujing Zhang et al. discussed the main epigenetic drugs targeting LSD1 for AML therapy. [Read the Full Post]

Inhibition of Methyltransferase DOT1L Sensitizes to Sorafenib Treatment AML Cells Irrespective of MLL-Rearrangements: A Novel Therapeutic Strategy for Pediatric AML

36 | Dec 09 2020

Annalisa Lonetti et al. highlighted a novel therapeutic strategy for pediatric AML patients. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 | Nov 14 2020

Laurie K Svoboda et al. demonstrated that the SSP was highly active in Ewing sarcoma and that its oncogenic activation was maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

Nullifying epigenetic writer DOT1L attenuates neointimal hyperplasia

63 | Sep 22 2020

Yitao Huang et al. presented a strong rationale for continued mechanistic and translational investigation into DOT1L targeting for treatment of (re)stenotic vascular conditions. [Read the Full Post]

Palmitate-TLR4 signaling regulates the histone demethylase, JMJD3, in macrophages and impairs diabetic wound healing

68 | Aug 31 2020

Frank M Davis et al. concluded that palmitate contributed to the chronic Jmjd3-mediated activation of macrophages in diabetic peripheral tissue and a histone demethylase inhibitor-based therapy might represent a novel treatment for nonhealing diabetic wounds. [Read the Full Post]

EZH2 Supports Osteoclast Differentiation and Bone Resorption Via Epigenetic and Cytoplasmic Targets

77 | Aug 08 2020

Juraj Adamik et al. found that EZH2 exhibits complex roles in supporting osteoclast differentiation and function. [Read the Full Post]

PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity

107 | Aug 03 2020

Hyungsoo Kim et al. provided a rationale to test PRMT5 inhibitors in immunotherapy-based clinical trials as a means to enhance an antitumor immune response. [Read the Full Post]

HMTase Inhibitors as a Potential Epigenetic-Based Therapeutic Approach for Friedreich's Ataxia

128 | Jun 28 2020

Mursal Sherzai et al. showed that a combination treatment of BIX0194 and GSK126, significantly increased FXN gene expression levels and reduced the repressive histone marks. However, no increase in frataxin protein levels was observed. [Read the Full Post]

EZH2 Is Involved in Vulnerability to Neuroinflammation and Depression-Like Behaviors Induced by Chronic Stress in Different Aged Mice

118 | Jun 23 2020

Wei Wang et al. found that EZH2 might be involved in susceptibility to neuroinflammation and depression-like behaviors in different aged mice. [Read the Full Post]

The DOT1L inhibitor Pinometostat decreases the host-response against infections: Considerations about its use in human therapy

198 | Mar 03 2020

Marcos-Villar Let al. supported a possible increased vulnerability to infection in MLL-r leukemia patients undergoing pinometostat treatment. Close follow up of infection should be considered in pinometostat therapy to reduce some severe side effects during the treatment. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 | Feb 04 2020

Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway

205 | Jan 31 2020

Zhang H et al. demonstrated that reactivation of BAI1 expression underlies EPZ-6438 antitumorigenic action, and provided preclinical proof-of-principle evidence for targeting EZH2 in patients with MB. [Read the Full Post]

Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer

432 | Nov 29 2019

Evanno E et al. showed that histone methylation was modified during EMT, and combination of epigenetic compounds with conventional or targeted chemotherapy might contribute to reduce metastasis and to enhance clinical responses. [Read the Full Post]

Epigenetic Profiling Identifies LIF as a Super-enhancer-Controlled Regulator of Stem Cell-like Properties in Osteosarcoma

236 | Nov 12 2019

Lu B et al. revealed osteosarcoma SE profiles and uncovers a distinct tumor-stemness epigenetic regulatory mechanism in which an osteosarcoma-specific SE-mediated factor, LIF, promotes osteosarcoma stemness gene activation via NOTCH1 signaling pathway. [Read the Full Post]

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

264 | Oct 16 2019

AbuHammad S et al. provided a strong rationale for further investigation of novel combinations of CDK4/6 and PRMT5 inhibitors, not only in melanoma but other tumor types, including breast, pancreatic, and esophageal carcinoma. [Read the Full Post]

Blocking EZH2 methylation transferase activity by GSK126 decreases stem cell-like myeloma cells

0 | Aug 27 2019

Zeng D et al. suggested that EZH2 inactivation by GSK126 is effective in killing MM cells and CSCs as a single agent or in combination with bortezomib. Clinical trial of GSK126in patients with MM may be warranted. [Read the Full Post]

Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma

281 | Aug 19 2019

Knutson SK et al. indicated these data confirm the dependency of EZH2-mutant NHL on EZH2 activity and portend the utility of EPZ-6438 as a potential treatment for these genetically defined cancers. [Read the Full Post]

A patent review of arginine methyltransferase inhibitors (2010-2018)

307 | Jul 10 2019

Li X et al. summarized the updated patented inhibitors targeting PRMTs from 2010 to 2018. The authors illustrate the chemical structures, molecular mechanism of action, pharmacological activities as well as the potential clinical application including combination therapy and biomarker-guided therapy. PRMT inhibitors in clinical trials are also highlighted. The authors provide a future perspective for further development of potent and selective PRMT inhibitors. [Read the Full Post]

Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells

280 | Jun 26 2019

Cao YP et al. demonstrated that G9a may be a promising therapeutic target for UBC, and an epigenetics-based therapy by UNC0642 is suggested. [Read the Full Post]

Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin

329 | Jun 06 2019

Wang Q et al. suggested that elevating H3K27me3 level can improve drug sensitivity in CRC patients. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

419 | May 09 2019

Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

502 | Mar 10 2019

Jabbour E et al. indicated that treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. [Read the Full Post]

Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

416 | Mar 06 2019

Bao B et al. indicated that H3K27me3 demethylation is a key epigenetic regulator in the process of hair cell regeneration in zebrafish and suggest that H3K27me3 histone demethylase activity might be a novel therapeutic target for the treatment of hearing loss. [Read the Full Post]

Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival

427 | Feb 27 2019

Zhang W et al. indicated that NPMc+ leukemic cell survival requires upregulation of PBX3 and HOXA9, and this action can be largely attenuated by a DOT1L inhibitor. [Read the Full Post]

Preclinical evaluation of the BET bromodomain inhibitor BAY 1238097 for the treatment of lymphoma

470 | Jan 02 2019

Bernasconi E et al. indicated the use of combination schemes targeting EZH2, mTOR and BTK alongside BET bromodomains. [Read the Full Post]

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

480 | Jan 02 2019

Parasramka M et al. showed that NEAT-1 is a downstream effector of gemcitabine sensitivity in CCA. The expression of BAP1 is a determinant of sensitivity to therapeutic drugs that can be exploited to enhance responses through combination strategies. [Read the Full Post]

Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification

458 | Dec 31 2018

Gherardi S et al. suggested therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation. [Read the Full Post]

Epigenetic drug combination induces remission in mouse xenograft models of pediatric acute myeloid leukemia

576 | Nov 18 2018

Gopalakrishnapillai A et al. indicated the expression of mutant p53 in MV4;11 cells reduced sensitivity to azacitidine-panobinostat combination, suggesting that p53 may be a predictor of response to epigenetic therapy in pediatric AML. [Read the Full Post]

Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma.

600 | Oct 12 2018

Tatekawa S et al. showed the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways. [Read the Full Post]

Multi-omics maps of cotton fibre reveal epigenetic basis for staged single-cell differentiation

765 | May 06 2018

Wang M et al. illustrated two divergent pathways mediating a continuous increase of DNA methylation and also sheds further light on the epigenetic basis for single-cell differentiation in plants. [Read the Full Post]