Gefitinib resistance remains a major obstacle to the effective treatment of non-small cell lung cancer (NSCLC), and the underlying molecular mechanisms have not yet been fully elucidated. Lysosomal-associated transmembrane protein 4B (LAPTM4B) has been shown to be involved in cancer progression, but its specific role in gefitinib resistance and the prognosis of NSCLC patients remains unclear. In this study, we conducted functional experiments including CCK-8, Transwell, and tumor sphere formation assays in LAPTM4B-overexpressing or knockdown HCC827 cells and gefitinib-resistant HCC827-R cells. In vivo validation was performed using a NSCLC xenograft model in nude mice. The results showed that LAPTM4B was upregulated in NSCLC, with a further increase in gefitinib-resistant NSCLC samples. Functional experiments demonstrated that knockdown or overexpression of LAPTM4B regulated gefitinib resistance, cell migration, and stemness in HCC827 cells. Furthermore, RPS3 was identified as a key interacting target of LAPTM4B, and LAPTM4B could enhance the stability of RPS3 protein by inhibiting its ubiquitination. In vivo xenograft experiments showed that knockdown of LAPTM4B significantly suppressed tumor growth and tumor stemness, and this inhibitory effect could be reversed by overexpression of RPS3. Collectively, our findings indicate that LAPTM4B promotes gefitinib resistance and NSCLC progression by stabilizing RPS3 protein through inhibiting its ubiquitination, and the LAPTM4B-RPS3 axis may serve as a potential therapeutic target for overcoming gefitinib resistance in NSCLC.
Yu Jiang, Wen-Jing Xie, Rong-Wei Chen et al.· Biochimica et biophysica act...· 0 citations
Background Carbapenem−resistant Acinetobacter baumannii (CRAB) is a major threat to hospitalised patients, particularly in intensive care units and orthopaedic wards where implant−associated infections are common. However, the genomic and biofilm characteristics of CRAB in orthopaedic specialty hospitals remain poorly understood. Methods A total of 97 non-duplicate CRAB isolates collected between 2024 and 2025 were included. Antimicrobial susceptibility testing was performed using the VITEK-2 system, and biofilm formation was quantitatively assessed by the crystal violet method. Whole-genome sequencing (WGS) was carried out on the Illumina platform to analyse multilocus sequence typing (MLST), capsular types, resistance genes and virulence genes. A phylogenetic tree was constructed based on single-nucleotide polymorphisms (SNPs). Results ST2 was the dominant clone (95.88%) among the 97 isolates, and KL3 was the most prevalent capsular type (83.51%). All isolates carried intrinsic blaOXA-51-like genes, predominantly blaOXA-66 (95.88%). The most common acquired carbapenemase gene was blaOXA-23 (98.97%), and two isolates carried metallo-β-lactamase (MBL) genes (blaNDM-1 and blaNDM-5, respectively). All isolates exhibited a multidrug-resistant phenotype, with low resistance rates to tigecycline (6.19%) and minocycline (7.22%), and all remained susceptible to colistin. Strong biofilm formers accounted for 91.75% of isolates, and the carriage rates of biofilm-associated genes (bap, csuABCDE, pgaABCD) exceeded 90%. Phylogenetic analysis grouped the isolates into three clonal clades, with the majority (88.66%) falling into Clade C (ST2/KL3). This clade had been circulating in China as an outbreak lineage since 2018, gradually replacing Clade B (ST2/KL2), and became the dominant clone in 2024–2025. Conclusion CRAB isolates in this orthopaedic specialty hospital are dominated by the ST2/KL3 clone, which carries multiple resistance and virulence genes, exhibits a remarkably strong biofilm-forming ability, and shows a capsular switch trend from KL2 to KL3. Enhanced molecular surveillance of this dominant clone and increased attention to anti-biofilm strategies for orthopaedic implant-related infections are strongly recommended.
Tengfei Shi, Shaohan Xu, Xuexin Zheng et al.· Frontiers in Cellular and In...· 0 citations