CBX1 is involved in hepatocellular carcinoma progression and resistance to sorafenib and lenvatinib via IGF-1R/AKT/SNAIL signaling pathway
Lenvatinib
Surgical oncology
DOI:
10.1007/s12072-024-10696-0
Publication Date:
2024-05-20T18:02:33Z
AUTHORS (7)
ABSTRACT
Abstract Background Chromobox Homolog 1 (CBX1) plays a crucial role in the pathogenesis of numerous diseases, including evolution and advancement diverse cancers. The CBX1 pan-cancer its mechanism hepatocellular carcinoma (HCC), however, remains to be further investigated. Methods Bioinformatics approaches were harnessed scrutinize CBX1’s expression profile, association with tumor staging, potential impact on patient outcomes across various Single-cell RNA sequencing data facilitated investigation patterns at individual cell level. levels HCC adjacent non-tumor tissues quantified through Real-Time Polymerase Chain Reaction (RT-PCR), Western Blotting (WB), Immunohistochemical analyses. A tissue microarray was employed explore relationship between levels, prognosis, clinicopathological characteristics HCC. Various vitro assays—including CCK-8, colony formation, Transwell invasion, scratch tests—were conducted assess proliferative motility properties cells upon modulation expression. Moreover, functional discerned xenograft studies nude mice. Results found upregulated most cancer forms, heightened correlating adverse prognoses. Within context HCC, elevated consistently indicative poorer clinical outcomes. Suppression knockdown methodologies markedly diminished proliferation, invasive capabilities, migratory activity, Epithelial−mesenchymal transition (EMT) processes, resistance Tyrosine kinase inhibitors (TKIs). Contrastingly, augmentation opposite effects. Subsequent investigative efforts revealed promoter EMT contributor increased TKI within cells, mediated via IGF-1R/AKT/SNAIL signaling axis. oncogenic activities proved attenuable either by AKT pathway inhibition or targeted silencing IGF-1R. Conclusions broad overexpression specifically positions it as putative entity. It is implicated forwarding progression exacerbating interaction cascade.
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