An array of gene silencing pathways share a common early step: Dicer cleaves double-stranded RNA (dsRNA) into approximately 20-25 nucleotide fragments that direct the silencing machinery to specific targets. A recent report in Cell reveals how Dicer's two RNase III domains collaborate during dsRNA processing and sets the stage for a deeper understanding of Dicer's roles in later phases of silencing complex assembly.
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http://dx.doi.org/10.1016/j.molcel.2004.07.002 | DOI Listing |
Onco Targets Ther
January 2025
Department of Gynecology, Sichuan Provincial Hospital of Traditional Chinese Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People's Republic of China.
Background: Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion is crucial for autophagy, making YKT6, a key modulator of cell membrane fusion, a potential target for cancer therapy. However, its oncogenic role across different cancers remains unclear. This study was to investigate the prognostic value and potential immunological functions of YKT6, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).
View Article and Find Full Text PDFViruses
January 2025
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus-HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)-, to study betacoronavirus interactions with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation.
View Article and Find Full Text PDFCurr Gene Ther
January 2025
Department of Pharmacology, Faculty of Medicine, The University of Jordan, Queen Rania Al-Abdullah Street, Amman 11942, Jordan.
Introduction: Liposomes are versatile delivery systems for encapsulating small interfering RNAs (siRNAs) because they enhance cellular uptake and gene silencing. This study compares the new liposome formula to commercial lipofectamine in delivering siRNAs targeting hepatic carcinoma genes, focusing on HNF4-α and PFKFB4.
Methods: Flow cytometry and confocal microscopy revealed efficient internalization of PE-Rhod- B labeled lipoplexes in HepG2 cells, while cytotoxicity assays demonstrated significant reductions in cell viability, particularly with siHNF4-α and siPFKFB4.
Blood Adv
January 2025
Department of Internal Medicine, Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Treatment options for the bleeding disorder von Willebrand disease type 2B (VWD2B) are insufficient and fail to address the negative effects of circulating mutant von Willebrand factor (VWF). The dominant-negative nature of VWD2B makes functionally defective VWF an interesting therapeutic target. Previous in vitro studies have demonstrated the feasibility of allele-selective silencing of mutant VWF using small interfering RNAs (siRNAs) targeting common single nucleotide polymorphisms (SNPs) in the human VWF gene, an approach that can be applied irrespective of the disease-causing VWF mutation.
View Article and Find Full Text PDFCancer Sci
January 2025
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Effective therapeutic strategies for epithelioid sarcoma (EpS), a high-grade soft tissue sarcoma characterized by loss of integrase interactor 1 (INI1), have not yet been developed. The present study therefore investigated the association between INI1 loss and upregulation of the aurora kinase A (AURKA)/polo-like kinase 1 (PLK1)/cell division cycle 25C (CDC25C) axis, as well as the therapeutic relevance of this axis in EpS. Notably, our findings showed that the reintroduction of INI1 in VA-ES-BJ cells significantly reduced proliferation, mitigated tumorigenicity, and negatively regulated the expression of AURKA and its downstream effectors, as well as the activation of PLK1 and CDC25C.
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