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Heat shock protein family D member 1 (HSPD1) modulates ribosome-related pathways and protein synthesis in lung adenocarcinoma
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DOI:10.1007/s11010-026-05693-w.png)
Abstract
En 中文
Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer. Heat shock protein family D member 1 (HSPD1 or HSP60), a multifunctional chaperone, has been implicated in promoting lung cancer progression by regulating tumor cell growth, cancer-associated fibroblast activation, and angiogenesis. Despite these roles, the molecular mechanisms underlying its oncogenic activity remain incompletely understood. In this study, we conducted a proteomic analysis and functional investigations on HSPD1-knockdown and control A549 cells. Knockdown of HSPD1 suppressed cell proliferation, disrupted cell-cycle progression, and had no significant effect on apoptosis. Additionally, HSPD1-knockdown cells exhibited reduced colony formation, wound closure, and invasion capabilities. Sequential Window Acquisition of All Theoretical fragment ions (SWATH)-targeted proteomics revealed 21 significantly altered proteins, primarily involved in ribosome-related functions and associated with overall survival in LUAD patients. Reduced levels of ribosomal proteins and translational capacity were further examined by Western blot and protein synthesis assays. A decrease in ribosome abundance was confirmed by immunofluorescence staining of ribosomal protein S3 (RPS3) and by direct visualization under transmission electron microscopy. Quantitative real-time PCR demonstrated downregulation of MTOR in HSPD1-knockdown cells. Moreover, HSPD1 knockdown sensitized cells to homoharringtonine, a chemotherapeutic drug targeting ribosomal activity. These effects on cell proliferation, ribosomal protein levels, and drug sensitivity were validated in an independent LUAD cell line, H1975. Collectively, these findings indicate that HSPD1 acts as an oncogenic driver in LUAD by modulating ribosome-related pathways and protein synthesis.
Keywords:
HSPD1
HSP60
shRNA knockdown
LUAD
Ribosome
Translational regulation
Quantitative proteomics
Journal
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