FASEB JOURNAL
·
2025
·Vol. 39
·期 6
·e70345
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IF 4.2
Pengfei Luo,Zhimin Li,Haodong He,Yuanbin Tang,Lijun Zeng,Lunqi Luo,Lianjie Ouyang,Meiling Wen,Yuehua Li,Yongjun Jiang
The ribophorin family, including RPN1, has been associated with tumor progression, but its specific role in pan-cancer dynamics remains unclear. Using data from TCGA, GTEx, and Ualcan databases, we investigated the relationship of RPN1 with prognosis, genomic alterations, and epigenetic modifications across various cancers. Differential analysis revealed elevated RPN1 expression in multiple cancer types, indicating a potential prognostic value. Amplification was the predominant mutation type of RPN1 in pan-cancer, with notable correlations with DNA methylation and copy number variation. Gene set variation analysis identified RPN1's involvement in cancer development, immunity, and metabolism. Additionally, RPN1 expression correlated with the tumor microenvironment, immune response factors, and response to anti-tumor therapies. Functional validation in triple-negative breast cancer, glioblastoma, and bladder cancer cell lines demonstrated the role of RPN1 in tumor cell proliferation and migration. Our findings highlight RPN1 as a potential biomarker for cancer diagnosis and treatment response in pan-cancer therapy. Graphical The multifaceted role of RPN1 in cancer progression: from gene expression to immunotherapy potential. The graphical abstract illustrates the multifaceted role of RPN1 in cancer. Elevated RPN1 expression is closely linked to reduced survival rates and altered immune activity from normal to cancer cells. It highlights RPN1's interaction with the tumor microenvironment, including its correlation with immune cells (e.g., CD8+ T cells, tumor-associated macrophages, CAFs) and synergy with PD-L1 expression. The study reveals RPN1's role in tumor immune suppression and its potential as a biomarker for predicting immunotherapy response and assessing prognosis.
研究领域:
肿瘤学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·Vol. 27
·期 11
·1611-1628
·
IF 1.6
Pan Chengzhen,Zhang Chi,Lin Zonghan,Liang Zhou,Cui Yinhang,Shang Zhihao,Wei Yuanxun,Chen Feng
Background: Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism related to disulfidptosis, a newly discovered cell death mechanism, remains unclear. Objective: The study
aimed to investigate the biological function and immune mechanism of disulfidptosis- related ribophorin I (RPN1) in OP and to experimentally confirm that RPN1 is the target for the treatment of OP with kaempferol. Methods: Differential expression analysis was conducted on disulfide-related
genes extracted from the GSE56815 and GSE7158 datasets. Four machine learning algorithms identified disease signature genes, with RPN1 identified as a significant risk factor for OP through the nomogram. Validation of RPN1 differential expression in OP patients was performed using the GSE56116
dataset. The impact of RPN1 on immune alterations and biological processes was explored. Predictive ceRNA regulatory networks associated with RPN1 were generated via miRanda, miRDB, and TargetScan databases. Molecular docking estimated the binding model between kaempferol and RPN1. The targeting
mechanism of kaempferol on RPN1 was confirmed through pathological HE staining and immunohistochemistry in ovariectomized (OVX) rats. Results: RPN1 was abnormally overexpressed in the OP cohort, associated with TNF signaling, hematopoietic cell lineage, and NF-kappa B pathway. Immune
infiltration analysis showed a positive correlation between RPN1 expression and CD8+ T cells and resting NK cells, while a negative correlation with CD4+ naive T cells, macrophage M1, T cell gamma delta, T cell follicular helper cells, activated mast cells, NK cells, and dendritic cells, was
found. Four miRNAs and 17 lncRNAs associated with RPN1 were identified. Kaempferol exhibited high binding affinity (-7.2 kcal/mol) and good stability towards the RPN1. The experimental results verified that kaempferol could improve bone microstructure destruction and reverse the abnormally
high expression of RPN1 in the femur of ovariectomized rats. Conclusion: RPN1 may be a new diagnostic biomarker in patients with OP, and may serve as a new target for kaempferol to improve OP.
研究领域:
医学研究
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药理学
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分子生物学
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免疫学
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生物信息学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 12
·1543
·
IF 4.9
Min Li,Wenying Li,Fang Xu,Yiping Pu,Jianguang Li
Background:L-Shikonin, an active component of Arnebia euchroma (Royle) Johnst., has remarkable pharmacological effects, particularly in its anti-tumour activity. Nonetheless, the specific targets and mechanisms of action remain to be further explored.Methods:A novel Fe3O4@L-Shikoninwas designed and synthesized in this study by linking Fe3O4andL-Shikoninthrough benzophenone. Fe3O4@L-Shikoninwas characterized using several techniques, including scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and drug removal methods, to determine the content ofL-Shikoninon the surface of the magnetic particles. Target hooking technology was utilized to identify the target proteins of the compound in melanoma. The synthesized Fe3O4@L-Shikoninwas co-incubated with A375 cell lysate, followed by the target proteins, which were purified by magnetic enrichment using magnetic microspheres and identified by high-resolution mass spectrometry.Results:AutoDock Vina software was employed for molecular docking analysis, where it was found thatL-Shikonintargets RPN1, CPEB4, and HNRNPUL1 proteins. Subsequently, A375 cells were treated withL-Shikoninat different concentrations (2.5, 5.0, 10.0 μM) for 48 h, and the expressions of the three proteins were observed. The results showed a significant reduction in the relative expression of CPEB4 in the high-dose group compared to the control group (p< 0.01). Moreover, the relative expression of HNRNPUL1 was decreased in the medium- and high-dose groups (p< 0.05).Conclusions:This study initially revealed from the source thatL-Shikoninmay regulate melanoma-specific markers, melanosomes, tyrosine kinases related to abnormal tyrosine metabolism, and melanoma through multiple targets such as CPEB4 and HNRNPUL1. Proliferation and metastasis work together to exert an anti-melanoma mechanism, which provides a new idea for the follow-up study of the molecular pharmacological mechanism of the complex system of total naphthoquinones inArnebia euchroma(Royle) Johns.
研究领域:
药理学
·
肿瘤学
·
分子生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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