Oncologie
·
2024
·
IF 1.4
Chenchen Jin,Xuejiao Xu,Tao Li,Chunxue Zhang,Jianqing Peng,Chao Liu,Weifeng Zheng,Xu Zhang
Objectives
Colorectal cancer (CRC) is a global challenge, and heat shock protein 90 (HSP90) is identified as a key driver in cancer progression. However, the tumor-promoting mechanism of HSP90 in CRC, particularly HSP90AB1, remains unclear. This study aims to explore and analyze the oncogenic mechanism of HSP90AB1 in CRC and identify potential therapeutic targets.
Materials and methods
HSP90AB1 expression underwent analysis in CRC cell lines and tissues at mRNA and protein levels. Through the use of shRNA, targeted suppression of HSP90AB1 was achieved in CRC cell lines, enabling analysis of its influence on cell proliferation, invasion, apoptosis, and cell cycle progression. Subsequent investigation focused on elucidating the regulatory relationship between HSP90AB1 and IDO1, employing a combination of bioinformatics approaches and in vitro /vivo experiments. These efforts confirmed IDO1 as a downstream target of HSP90AB1 and provided insight into its role in driving CRC progression.
Results
HSP90AB1 exhibits overexpression in both CRC cell lines and tumor tissues (p<0.05). Its downregulation impedes cell proliferation and invasion (p<0.01), promotes apoptosis and cell cycle arrest (p<0.05). Investigation reveals that decreased HSP90AB1 leads to the inhibition of IDO1 (p<0.01), suggesting that IDO1 regulation plays a crucial role in mediating the pro-tumorigenic effects of HSP90AB1. In vivo experiments confirm the substantial reduction in tumor growth upon HSP90AB1 knockdown in xenograft models (p<0.01). However, this tumor-suppressive effect is reversed upon IDO1 overexpression (p<0.01), highlighting IDO1 as a downstream target of HSP90AB1 in CRC progression.
Conclusions
HSP90AB1 exerts a regulatory role in the progression of CRC by upregulating IDO1.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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产品关联
DOI
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 29
·15857-15868
·
IF 6.895
Shang Liu,Xinbang Jiang,Xuejiao Tian,Zhenzhen Wang,Zhen Xing,Jiahui Chen,Junfeng Zhang,Chunming Wang,Lei Dong
The protein corona influences and determines the biological function of nanoparticles (NPs) in vivo. Analysis and understanding of the activities of proteins in coronas are crucial for nanobiology and nanomedicine research. Misfolded proteins in the corona of NPs theoretically exist, and a protein denaturation-related cellular response might occur in this process as well as in related diseases. The exact evaluation of protein denaturation in the corona is valuable to assess the bioactivities of NPs. Here, we found that the level of adsorbed heat shock protein 90 kDa α class B member 1 (Hsp90ab1) by the denatured protein in iron–cobalt–nickel alloy NPs (FeCoNi NPs) and iron oxide NPs (Fe3O4 NPs) was correlated with circular dichroism (CD) analysis and 1-anilinonaphthalene-8-sulfonate (ANS) analysis. The content of Hsp90ab1 in the corona could be easily analysed by western blotting (WB). Further analysis suggested that the method could precisely show the time-dependent protein denaturation on Fe3O4 NPs, as well as the influence of the size and the surface modification. More importantly, this method could be applied to other proteins, like lysozyme, other than albumin. Based on the results and the correlation analysis, incubation and detection of Hsp90ab1 in the NP–corona complex can be used as a new and feasible method to evaluate protein denaturation induced by NPs.
研究领域:
纳米生物技术
·
纳米医学
·
蛋白质化学
·
生物物理学
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DOI
PubMed
高影响因子
Applied Biological Chemistry
·
2026
·Vol. 69
·期 1
·68
·
IF 4.2
Wang Yujie,Wang Jiajie,Cai Maoxuan,Ren Jie,Jia Fang,Jiang Wenjie,Su Dan,Yang Hao,Chen Guilin
Diabetic nephropathy (DN) ranks as the primary contributor to end-stage renal disease across the globe, characterized by progressive glomerular mesangial proliferation and tubular interstitial fibrosis, which poses a severe threat to public health. Pinocembrin is a major flavonoid compound that has been reported to exhibit a variety of prominent biological effects. However, its dual regulatory effects on glomerular and tubular injuries in DN remain unclear. The present study aims to investigate the potential role of pinocembrin in alleviating the progression of DN, providing a combination therapeutic strategy. In vivo experiments were performed to verify its efficacy in improving renal injury and fibrosis of pinocembrin in Lep db /Lep db ( db/db) mice. Pinocembrin-related targets were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP), Comparative Toxigenomics Database (CTD), Swiss Target Prediction, and Symmap databases. Differentially expressed genes in DN tubules and glomeruli were obtained from Gene Expression Omnibus (GEO) dataset GSE30122. Overlapping targets between pinocembrin and DN tissues were identified, followed by Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular docking predicted potential binding interactions between pinocembrin and key targets. In vitro experiments demonstrated that in HG-induced HK-2 cells, pinocembrin might target HSP90AB1 to suppress inflammatory response and epithelial-mesenchymal transition, thereby alleviating tubular fibrosis injury. In HG-treated SV40 cells, pinocembrin downregulated expression of VEGFR, thereby inhibiting cell proliferation and extracellular matrix deposition to improve glomerular pathological damage. This study clarifies the dual protective mechanism of pinocembrin on DN via regulatory pathways. These findings provide experimental foundation and theoretical insight for the application of pinocembrin as a functional food ingredient for the prevention and treatment of DN.
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DOI
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Shang Liu,Zhenzhen Wang,Xinbang Jiang,Jingjing Gan,Xuejiao Tian,Zhen Xing,Yiqing Yan,Jiahui Chen,Junfeng Zhang,Chunming Wang,Lei Dong
Biomolecular corona formed on nanoparticles (NPs) influences the latter's in vivo biological effects. Nanomaterials with different physicochemical properties exert similar adverse effects, such as cytotoxicity, suggesting the existence of ubiquitous signals during various corona formations that mediate common and fundamental cellular events. Here, we discover the involvement of the unfolded protein response (UPR) and recruited chaperones in the corona. Specially, heat shock protein 90 kDa α class B member 1 (Hsp90ab1) is abundantly enriched in the corona, accompanied by substantial aggregation of misfolded protein on particles intracellularly. Further analysis reveals the particulate matter 2.5 (PM2.5) and metal-containing particles are more capable of denaturing proteins. The recruited Hsp90ab1 activates diverse NPs' pathological behaviour by heat stress response (HSR), which were significantly reversed by geldanamycin (GA), the inhibitor of Hsp90ab1. Murine lung inflammation induced by PM2.5 and iron oxide NPs (Fe 3 O 4 NPs) is suppressed by GA, highlighting that Hsp90ab1-mediated UPR is a potential target for the treatment of environmental pollution-related illnesses. Based on our findings, the UPR and Hsp90ab1 presented in the corona of particles initiate fundamental intracellular reactions that lead to common pathological outcomes, which may provide new insights for understanding nanotoxicity and designing therapeutic approaches for diseases associated with environmental pollution.
研究领域:
纳米技术
·
毒理学
·
环境科学
·
细胞生物学
·
药理学
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DOI
PubMed
高影响因子
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