Inhibition of DNMT1 methyltransferase activity via glucose-regulated -GlcNAcylation alters the epigenome.

The DNA methyltransferase activity of DNMT1 is vital for genomic maintenance of DNA methylation. We report here that DNMT1 function is regulated by -GlcNAcylation, a protein modification that is sensitive to glucose levels, and that elevated -GlcNAcylation of DNMT1 from high glucose environment leads to alterations to the epigenome. Using mass spectrometry and complementary alanine mutation experiments, we identified S878 as the major residue that is -GlcNAcylated on human DNMT1.

Early Diagnostic Ability of Human Complement Factor B in Pancreatic Cancer Is Partly Linked to Its Potential Tumor-Promoting Role.

Although plasma complement factor B (CFB, NX_P00751), both alone and in combination with CA19-9 (i.e., the ComB-CAN), previously exhibited a reliable diagnostic ability for pancreatic cancer (PC), its detectability of the early stages and the cancer detection mechanism remained elusive.

Electrochemical Generation of Mesopores and Residual Oxygen for the Enhanced Activity of Silver Electrocatalysts.

The development of stable and efficient electrocatalysts is of key importance for the establishment of a sustainable society. The activity of a metal electrocatalyst is determined by its electrochemically active surface area and intrinsic activity, which can be increased using highly porous structures and heteroatomic doping, respectively. Herein, we propose a general strategy of generating mesopores and residual oxygen in metal electrocatalysts by reduction of metastable metal oxides using AgO electrodeposited onto carbon paper as a model system and demonstrating that the obtained multipurpose porous Ag electrocatalyst has high activity for the electroreduction of O and CO.

Potential Regulatory Role of Human-Carboxylesterase-1 Glycosylation in Liver Cancer Cell Growth.

We previously reported that human carboxylesterase 1 (CES1), a serine esterase containing a unique -linked glycosyl group at Asn79 (N79 CES1), is a candidate serological marker of hepatocellular carcinoma (HCC). CES1 is normally present at low-to-undetectable levels in normal human plasma, HCC tumors, and major liver cancer cell lines. To investigate the potential mechanism underlying the suppression of CES1 expression in liver cancer cells, we took advantage of the low detectability of this marker in tumors by overexpressing in multiple HCC cell lines, including stable Hep3B cells.

Identification of ALDH6A1 as a Potential Molecular Signature in Hepatocellular Carcinoma via Quantitative Profiling of the Mitochondrial Proteome.

Various liver diseases, including hepatocellular carcinoma (HCC), have been linked to mitochondrial dysfunction, reduction of reactive oxygen species (ROS), and elevation of nitric oxide (NO). In this study, we subjected the human liver mitochondrial proteome to extensive quantitative proteomic profiling analysis and molecular characterization to identify potential signatures indicative of cancer cell growth and progression. Sequential proteomic analysis identified 2452 mitochondrial proteins, of which 1464 and 2010 were classified as nontumor and tumor (HCC) mitochondrial proteins, respectively, with 1022 overlaps.

KCNH2-3.1 mediates aberrant complement activation and impaired hippocampal-medial prefrontal circuitry associated with working memory deficits.

Increased expression of the 3.1 isoform of the KCNH2 potassium channel has been associated with cognitive dysfunction and with schizophrenia, yet little is known about the underlying pathophysiological mechanisms. Here, by using in vivo wireless local field potential recordings during working memory processing, in vitro brain slice whole-cell patching recordings and in vivo stereotaxic hippocampal injection of AAV-encoded expression, we identified specific and delayed disruption of hippocampal-mPFC synaptic transmission and functional connectivity associated with reductions of SERPING1, CFH, and CD74 in the KCNH2-3.

FusionPro, a Versatile Proteogenomic Tool for Identification of Novel Fusion Transcripts and Their Potential Translation Products in Cancer Cells.

Fusion proteoforms are translation products derived from gene fusion. Although very rare, the fusion proteoforms play important roles in biomedical science. For example, fusion proteoforms influence the development of tumors by serving as cancer markers or cell cycle regulators.

-GlcNAcylation of the Tumor Suppressor FOXO3 Triggers Aberrant Cancer Cell Growth.

Posttranslational modifications of tumor suppressors can induce abnormal cell growth. Here, we identify site-specific -GlcNAcylation as a critical block of FOXO3 that may abrogate a part of the p53 pathway, resulting in aberrant cancer cell growth. Of seven -GlcNAcylation sites identified within the FOXO3 transactivation domain, we found that changes in -GlcNAcylation at Ser284 modulated p21-mediated cancer cell growth.

Long-lasting changes in DNA methylation following short-term hypoxic exposure in primary hippocampal neuronal cultures.

While the effects of hypoxia on gene expression have been investigated in the CNS to some extent, we currently do not know what role epigenetics plays in the transcription of many genes during such hypoxic stress. To start understanding the role of epigenetic changes during hypoxia, we investigated the long-term effect of hypoxia on gene expression and DNA methylation in hippocampal neuronal cells. Primary murine hippocampal neuronal cells were cultured for 7 days.

Anti-Cancer Effect of Ginsenoside F2 against Glioblastoma Multiforme in Xenograft Model in SD Rats.

The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside F2 (F2) to treat GBM.