Abstract 

The rise in the incidences of lung cancer currently poses a global health challenge, making it crucial to understand the underlying molecular and cellular mechanisms. Host cell factor-1 (HCF-1), a conserved epigenetic transcriptional coregulator, undergoes proteolytic maturation and glycosylation by O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). Elevated O-GlcNAc and OGT levels have been observed in lung cancer, highlighting their potential significance in disease progression. In human lung cancer tissues, we observed a significant upregulation of HCF-1, which coincides with increased OGT, O-GlcNAc, and Nkx2.1 (a diagnostic marker for non-small cell lung cancer [NSCLSC]) levels. To further explore HCF-1’s role mechanistically, we utilized the NSCLC cell lines, where HCF-1 depletion resulted in reduced proliferation, O-GlcNAcylation, Nkx2.1 expression, and O-GlcNAcylated proteins upon wheat germ agglutinin (WGA) pull-down, reinforcing its role in lung cancer progression. Additionally, Nkx2.1-mediated conditional knockout of HCF-1 impaired murine lung development and cell proliferation. Interestingly, OGT inhibition with OSMI-1 also reduced HCF-1, Nkx2.1 levels, and proliferation, suggesting a role for O-GlcNAcylation in HCF-1-mediated signaling cascades. Thus, our findings elucidate the critical role of HCF-1 and O-GlcNAcylation in lung cancer pathogenesis. These insights not only deepen our understanding of lung cancer pathogenesis but also identify potential molecular targets for studies aimed at intervention. 

Abstract

Zebrafish (Danio rerio) has emerged as a promising model for the preclinical investigation of several nanomedicines and drug molecules due to their optical transparency, genetic similarity to Homo sapiens, genetic modification, in vivo disease model creation, fecundity, and cost-effectiveness. The zebrafish model is widely used to assess drug screening for treating several diseases, such as cardiovascular, cancer, hepatic, and neural diseases. Various nanomedicines also undergo preclinical screening in zebrafish models to study biodistribution, biotoxicity, systemic circulation, and therapeutic efficacy. This review comprehensively highlights the application of zebrafish models in preclinical screening of conventional drugs and nanomedicines for various diseases. It covers various drug-based studies for myopia, diabetes, neurodegenerative disorders, and toxicity assessments in zebrafish models. Furthermore, it discusses nanomedicine-based approaches, including polymeric micelles for bedaquiline delivery in tuberculosis, liposome-based drug carriers, and doxorubicin-loaded iron oxide nanoparticles. Lastly, we have presented a xenotransplanted human cancer cell-based zebrafish disease model for analyzing the efficacy of various cancer-treating drugs for the treatment of breast, lung, cervical, and ovarian cancer and leukemia. 

Hemlata et al., Journal of Drug Delivery Science and Technology, 2025