Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Published: September 2015
AI Article Synopsis
Article Abstract
Expression of the p53-inducible antiproliferative gene BTG2 is suppressed in many cancers in the absence of inactivating gene mutations, suggesting alternative mechanisms of silencing. Using a shRNA screen targeting 43 histone lysine methyltransferases (KMTs), we show that SETD1A suppresses BTG2 expression through its induction of several BTG2-targeting miRNAs. This indirect but highly specific mechanism, by which a chromatin regulator that mediates transcriptional activating marks can lead to the downregulation of a critical effector gene, is shared with multiple genes in the p53 pathway. Through such miRNA-dependent effects, SETD1A regulates cell cycle progression in vitro and modulates tumorigenesis in mouse xenograft models. Together, these observations help explain the remarkably specific genetic consequences associated with alterations in generic chromatin modulators in cancer.
Background: Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined. In this study, we aimed to explore the interplay between inflammation and mitochondrial dysfunction in IBM.
Human mesenchymal stromal cells (MSCs) are attractive for both medical practice and biomedical research. Nonfreezing short-term storage may provide safe and simple transportation and promote the practical use of MSCs. We aimed to determine the duration of efficient storage at ambient temperature (22°C) of human dermal MSCs in different three-dimensional organization and to investigate the role of cell metabolic mode in the resistance to the ambient storage damaging factors.
Adequate hypothermic storage of human mesenchymal stem cells (hMSCs) is of fundamental importance since they have been explored in several regenerative medicine initiatives. However, the actual clinical application of hMSCs necessitates hypothermic storage for long periods, a process that requires the use of non-toxic and efficient cryo-reagents capable of maintaining high viability and differentiating properties after thawing. Current cryopreservation methods are based on cryoprotectant agents (CPAs) containing dimethylsulphoxide (DMSO), which have been shown to be toxic for clinical applications.
Understanding the molecular signaling pathways of colorectal cancer (CRC) can be accepted as the first step in treatment strategy. Permanent mTOR signaling activation stimulates the CRC process via various biological processes. It supplies the survival of CRC stem cells, tumorigenesis, morbidity, and decreased response to drugs in CRC pathogenesis.
DNA methylation repatterning is an epigenomic component of plant stress response, but the extent that methylome data can elucidate changes in plant growth following stress onset is not known. We applied high-resolution DNA methylation analysis to decode plant responses to short- and long-term high light stress and, integrating with gene expression data, attempted to predict components of plant growth response. We identified 105 differentially methylated genes (DMGs) following 1 h of high light treatment and 193 DMGs following 1 week of intermittent high light treatment.
