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| http://dx.doi.org/10.1182/blood.2018892737 | DOI Listing |
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Centromere inactivation during aging can be rescued in human cells.
Mol Cell
January 2025
Center for Cancer Research, National Cancer Institute/NIH, Bethesda, MD 20892, USA. Electronic address:
Aging involves a range of genetic, epigenetic, and physiological alterations. A key characteristic of aged cells is the loss of global heterochromatin, accompanied by a reduction in canonical histone levels. In this study, we track the fate of centromeres in aged human fibroblasts and tissues and in various cellular senescent models.
View Article and Find Full Text PDFBackground: Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor in infants, and more than 60% of children with ATRT die from their tumor. ATRT is associated with mutational inactivation/deletion of , a member of the SWI/SNF chromatin remodeling complex, suggesting that epigenetic events play a critical role in tumor development and progression. Moreover, disruption of SWI/SNF allows unopposed activity of epigenetic repressors, which contribute to tumorigenicity.
View Article and Find Full Text PDFThe functional role of LncRNA HOXA-AS2 in multiple human cancers.
Pathol Res Pract
December 2024
Research Fellow School of Life Sciences, University of Sussex, Brighton, UK. Electronic address:
Humans have more than 270,000 lncRNAs. Among these, lncRNA HOXA-AS2 is considered a transformative gene involved in various cellular processes, including cell proliferation, apoptosis, migration, and invasion. Thus, it can be regarded as a potential tumor marker for both diagnosis and prognosis.
View Article and Find Full Text PDFDiscovery of novel dual-target inhibitors of LSD1/EGFR for non-small cell lung cancer therapy.
Acta Pharmacol Sin
January 2025
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350, China.
Histone lysine-specific demethylase 1 (LSD1) is overexpressed in various solid and hematological tumors, suggesting its potential as a therapeutic target, but there are currently no LSD1 inhibitors available on the market. In this study we employed a computer-guided approach to identify novel LSD1/EGFR dual inhibitors as a potential therapeutic agent for non-small cell lung cancer. Through a multi-stage virtual screening approach, we found L-1 and L-6, two compounds with unique scaffolds that effectively inhibit LSD1 with IC values of 6.
View Article and Find Full Text PDFMitochondrial-cytochrome c oxidase II promotes glutaminolysis to sustain tumor cell survival upon glucose deprivation.
Nat Commun
January 2025
Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
Glucose deprivation, a hallmark of the tumor microenvironment, compels tumor cells to seek alternative energy sources for survival and growth. Here, we show that glucose deprivation upregulates the expression of mitochondrial-cytochrome c oxidase II (MT-CO2), a subunit essential for the respiratory chain complex IV, in facilitating glutaminolysis and sustaining tumor cell survival. Mechanistically, glucose deprivation activates Ras signaling to enhance MT-CO2 transcription and inhibits IGF2BP3, an RNA-binding protein, to stabilize MT-CO2 mRNA.
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