AI Article Synopsis
Article Abstract
Genome-wide RNA interference (RNAi) with pooled and barcoded short-hairpin RNA (shRNA) libraries provides a powerful tool for identifying cellular components that are relevant to the modes/mechanisms of action (MoA) of bioactive compounds. shRNAs that affect cellular sensitivity to a given compound can be identified by deep sequencing of shRNA-specific barcodes. We used multiplex barcode sequencing technology by adding sample-specific index tags to PCR primers during sequence library preparation, enabling parallel analysis of multiple samples. An shRNA library screen with this system revealed that downregulation of ATP1A1, an α-subunit of Na/K ATPase, conferred significant sensitivity to aurilide B, a natural marine product that induces mitochondria-mediated apoptosis. Combined treatment with ouabain which inhibits Na/K ATPase by targeting α-subunits potentiated sensitivity to aurilide B, suggesting that ATP1A1 regulates mitochondria-mediated apoptosis. Our results indicate that multiplex sequencing facilitates the use of pooled shRNA library screening for the identification of combination drug therapy targets.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435677 | PMC |
| http://dx.doi.org/10.1038/s41598-017-02016-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Current and emerging PCSK9-directed therapies to reduce LDL-C and ASCVD risk: A state-of-the-art review.
Pharmacotherapy
December 2024
Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA.
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Lowering low-density lipoprotein cholesterol (LDL-C) levels is a primary strategy to reduce ASCVD risk. Although statin therapy remains the initial therapy of choice to reduce LDL-C and ASCVD risk, statin intolerance and suboptimal LDL-C lowering response prompts the need for additional non-statin therapies.
View Article and Find Full Text PDFIdentification of cepharanthine as an effective inhibitor of African swine fever virus replication.
Emerg Microbes Infect
December 2024
One Health Laboratory, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People's Republic of China.
African swine fever virus (ASFV) causes highly contagious swine disease, African swine fever (ASF), thereby posing a severe socioeconomic threat to the global pig industry and underscoring that effective antiviral therapies are urgently required. To identify safe and efficient anti-ASFV compounds, a natural compound library was screened by performing an established cell-based ELISA in an ASFV-infected porcine alveolar macrophage (PAM) model. In total, 6 effective anti-ASFV compounds with low cytotoxicity were identified.
View Article and Find Full Text PDFInhibiting UGCG prevents PRV infection by decreasing lysosome-associated autophage.
Int J Biol Macromol
December 2024
School of Food and Bioengineering, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan Province, People's Republic of China, Zhengzhou 450046, China. Electronic address:
Glucosylceramide synthase (UGCG) is a key enzyme that catalyzes the initial glycosylation step in the biosynthesis of glycosphingolipids (GSLs) derived from glucosylceramide. UGCG is closely associated with various cellular processes, including the cell cycle, angiogenesis, multidrug resistance, and pathogen invasion. In this study, a short hairpin RNA (shRNA) library designed to target key genes involved in the sphingolipid metabolic pathway was utilized to elucidate their roles in Pseudorabies Virus (PRV).
View Article and Find Full Text PDFZwitterionic Polymer Lipid Nanoparticles Enabling Selective Organ Targeting Delivery of Small Interfering RNA for the Treatment of Hepatic and Pulmonary Inflammation.
Small
December 2024
Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China.
Lipid nanoparticles (LNPs) are clinically advanced small interfering RNA (siRNA) carriers, which can prevent the breakdown of siRNA during delivery and deliver siRNA into the cytoplasm to down-regulate the target gene. However, clinical LNPs are limited to the liver, and enhancing extrahepatic targeting is vital to expand the application of LNPs in vivo. Here, zwitterionic polymer LNPs (ZP-LNPs) are assembled with the zwitterionic polymer polycarboxybetaine (PCB) modified 1,2-dimyristoylglycerol (DMG) lipid DMG-PCB can selectively deliver siRNA to liver and lung, respectively.
View Article and Find Full Text PDFSynthetic rescue of Xeroderma Pigmentosum C phenotype via PIK3C3 downregulation.
Cell Death Dis
November 2024
Univ. Grenoble Alpes, CEA, Inserm, IRIG, UA13 BGE, Biomics, Grenoble, France.
Xeroderma Pigmentosum C is a dermal hereditary disease caused by a mutation in the DNA damage recognition protein XPC that belongs to the Nucleotide excision repair pathway. XPC patients display heightened sensitivity to light and an inability to mend DNA damage caused by UV radiation, resulting in the accumulation of lesions that can transform into mutations and eventually lead to cancer. To address this issue, we conducted a screening of siRNAs targeting human kinases, given their involvement in various DNA repair pathways, aiming to restore normal cellular behavior.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!