Long non-coding RNAs (lncRNAs) are a large and diverse class of transcribed RNAs, which have been shown to play a significant role in developing cancer. In this study, we apply integrative modeling framework to integrate the DNA copy number variation (CNV), lncRNA expression, and downstream target protein expression to predict patient survival in breast cancer. We develop a 3-stage model combining a mechanical model (lncRNA regressed on CNV and target proteins regressed on lncRNA) and a clinical model (survival regressed on estimated effects from the mechanical models). Using lncRNAs (such as and ) along with their CNV, target protein expressions, and survival outcomes from The Cancer Genome Atlas (TCGA) database, we show that predicted mean square error and integrated Brier score (IBS) are both lower for the proposed 3-step integrated model than that of 2-step model. Therefore, the integrative model has better predictive ability than the 2-step model not considering target protein information.
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http://dx.doi.org/10.1177/1176935119871933 | DOI Listing |
Cell Rep
January 2025
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address:
Sterols target sterol-sensing domain (SSD) proteins to lower cholesterol and circulating and hepatic triglyceride levels, but the mechanism remains unclear. In this study, we identify acyl-coenzyme A (CoA) synthetase long-chain family member 1 (ACSL1) as a direct target of ergosterol (ES). The C-terminal domain of ACSL1 undergoes conformational changes from closed to open, and ES may target the drug-binding pocket in the acetyl-CoA synthetase-like domain 1 (ASLD1) of ACSL1 to stabilize the closed conformation and maintain its activity.
View Article and Find Full Text PDFGlycobiology
January 2025
Department of Biochemistry, Dorothy Crowfoot Hodgkin Building, University of Oxford, South Parks Road, OX1 3QU, United Kingdom.
Abdala is a COVID-19 vaccine produced in Pichia pastoris and is based on the receptor-binding domain (RBD) of the SARS-CoV-2 spike. Abdala is currently approved for use in multiple countries with clinical trials confirming its safety and efficacy in preventing severe illness and death. Although P.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Medical Biochemistry, Faculty of Medicine, Kahramanmaraş Sütçü İmam University, Kahramanmaraş, Turkey.
Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions of individuals. These diseases are characterized by pathological changes in various brain regions, specific genetic mutations associated with the disease, deposits of abnormal proteins, and the degeneration of neurological cells. As neurodegenerative disorders vary in their epidemiological characteristics and vulnerability of neurons, treatment of these diseases is usually aimed at slowing disease progression.
View Article and Find Full Text PDFDrug Dev Res
February 2025
South University School of Pharmacy, Savannah, Giorgia, USA.
KRAS is a proto-oncogene that is found to be mutated in 15% of all metastatic cancers with high prevalence in pancreatic, lung, and colorectal cancers. Additionally, patients harboring KRAS mutations respond poorly to standard cancer therapy. As a result, KRAS is seen as an attractive target for targeted anticancer therapy.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Cardiothoracic Surgery, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou City, Hubei Province, China.
Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease (CVD) that is partly attributable to endothelial dysfunction, inflammatory response, and angiogenesis. G protein-coupled receptor 4 (GPR4), a proton-sensitive G protein-coupled receptor that is abundantly expressed in vascular endothelial cells, has been associated with numerous physiological functions. Nevertheless, its potential involvement in the development of AAA remains unexplored.
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