Translational Oncology
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2023
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IF 5
Haibo Liu,Jie Zhang,Jiamin Li,Xiaoying Cao,Kai Yu,Xun Xia,Zongxi Li,Fengbo Wang
Background This study aimed to investigate the specific roles of the long non-coding RNA (lncRNA) proteasome 20S subunit beta 8 ( PSMB8 )-antisense RNA 1 ( AS1 )/microRNA ( miR ) -382–3p /branched-chain amino acid transaminase 1 ( BCAT1 ) interaction network in gliomas. Methods Western blotting and quantitative reverse transcription-polymerase chain reaction were performed to assess the expression levels of lncRNA PSMB8-AS1, BCAT1 , and miR-382-3p . Moreover, the cell proliferation, migration, and apoptosis were assessed using the cell counting kit-8, Transwell, and caspase-3 activity assays, respectively. The biological role of lncRNA PSMB8-AS1 in glioma was investigated in vivo using a xenograft mouse model. Additionally, the associations among lncRNA PSMB8-AS1, miR-382-3p , and BCAT1 were analyzed using dual-luciferase and RNA immunoprecipitation assays and bioinformatics analyses. Results Glioma cell lines and tissues exhibited overexpression of lncRNA PSMB8-AS1 and BCAT1 and low expression of miR-382-3p . Knockdown of PSMB8-AS1 remarkably repressed the tumor growth in vivo and the migration and proliferation of glioma cells in vitro . In contrast, knockdown of lncRNA PSMB8-AS1 increased the cell apoptosis. Mechanistically, PSMB8-AS1 directly targeted miR-382-3p . By sponging miR-382-3p , lncRNA PSMB8-AS1 stimulated the migration and proliferation of glioma cells and suppressed their apoptosis. Additionally, miR-382-3p directly targeted BCAT1 . Inhibition of miR-382-3p reversed the antitumor effects of BCAT1 silencing on glioma progression. Conclusion Our study revealed that lncRNA PSMB8-AS1 aggravated glioma malignancy by enhancing BCAT1 expression after competitively binding to miR-382-3p . Therefore, lncRNA PSMB8-AS1 may be a potential biomarker and therapeutic target for glioma treatment.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Gong Jing,Zhou Min,Huang Yue,Yu Mengjun,Zhou Qiang,Chen Shiwen,Wang Jia,Yang Min,Luo Qing,Zhang Rong,Huang Jingbin
Asthma is a chronic inflammatory respiratory disease worldwide. Its severe phenotypes, particularly the glucocorticoid-resistant ones, pose a major challenge, with neutrophilic inflammation being the key driver. However, no effective treatments are currently available. Herein, we report a macromolecular therapeutic strategy capable of targeting multiple key cells involved in the pathogenesis of neutrophilic asthma. The macromolecular therapy named PMART is constructed by conjugating artesunate and polyethylene glycol to the triazine scaffold. It is highly water-soluble and can self-assemble into nanomicelles, which enables efficient targeting to inflamed lung tissues and localization in inflammatory cells. In a murine model of neutrophilic asthma, PMART has proven to have in vivo efficacy equivalent to or greater than that of two clinically used anti-asthma drugs. Mechanistically, PMART reduces succinate levels by inhibiting branched-chain amino acid transaminase 1 (BCAT1) overexpression, thereby suppressing neutrophilic inflammation via blocking the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and the production of pro-inflammatory cytokines. Notably, PMART exhibits a favorable safety profile in mice. Taken together, these data support the potential of PMART as a novel and highly effective therapeutic agent for neutrophilic asthma and other neutrophil-mediated diseases. Graphical
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高影响因子
TOXICOLOGY
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2025
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IF 4.6
Ziyan Liu,Jingyu Wang,Wei Zhang,Huiwen Kang,Danyang Huang,Ziyan Wang,Guangyu Jiang,Ai Gao
The continuous accumulation of senescent hematopoietic stem progenitors (HSPCs) contributes to hematopoietic damage. Benzene is a confirmed human carcinogen, and its damage to HSPCs is a key event in benzene poisoning. However, whether the environmental dose of benzene is involved in HSPC damage by inducing cellular senescence has not been reported. Here, male C57BL/6 J mice were exposed to benzene vapour for 12 weeks (0, 10, 50 ppm), and mouse hematopoietic progenitor cell line FDC-P1 was exposed to benzene metabolite 1,4-BQ for 24 h (0, 5, 10 μM). In vivo and in vitro models combined with single-cell RNA sequencing have shown that benzene and its metabolites caused senescence in whole bone marrow and hematopoietic progenitor cells. Proteomics showed that benzene exposure significantly up-regulated interferon regulatory factor 4 (Irf4) in the bone marrow. Irf4 inhibition alleviated cellular senescence and hematopoietic damage, suggesting that Irf4 is a key molecule in benzene-induced hematopoietic cell senescence. Mechanistically, benzene caused a decrease in branched-chain amino acids (BCAAs) in whole bone marrow, hematopoietic progenitor cells, and plasma, and an increase in the BCAA catabolic enzyme Bcat1, mitochondrial ROS, and Bckdh activity. Irf4 inhibition down-regulated Bcat1, alleviated mitochondrial oxidative stress-dependent Bckdh abnormality, and up-regulated BCAAs. BCAA supplementation effectively alleviated benzene-induced cellular senescence and hematopoietic damage. In conclusion, the study identified that Irf4 triggered benzene-induced hematopoietic progenitor cell senescence and hematopoietic damage by mitochondrial injury-induced excessive BCAA catabolism. This study provides new ideas on the molecular mechanism of benzene-induced hematopoietic damage from the perspective of metabolism and senescence.
研究领域:
毒理学
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血液学
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分子生物学
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环境卫生
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代谢
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细胞生物学
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PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Jingyu Wang,Lin Han,Ziyan Liu,Wei Zhang,Lei Zhang,Jiaru Jing,Ai Gao
Benzene is the main environmental pollutant and risk factor of childhood leukemia and chronic benzene poisoning. Benzene exposure leads to hematopoietic stem and progenitor cell (HSPC) dysfunction and abnormal blood cell counts. However, the key regulatory targets and mechanisms of benzene hematotoxicity are unclear. In this study, we constructed a benzene-induced hematopoietic damage mouse model to explore the underlying mechanisms. We identified that Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was significantly reduced in benzene-exposed mice. Moreover, targeting IGF2BP1 effectively mitigated damages to hematopoietic function and hematopoietic molecule expression caused by benzene in mice. On the mechanics, by metabolomics and transcriptomics, we discovered that branched-chain amino acid (BCAA) metabolism and fatty acid oxidation were key metabolic pathways, and Branched-chain amino acid transaminase 1 (BCAT1) and Carnitine palmitoyltransferase 1a (CPT1A) were critical metabolic enzymes involved in IGF2BP1-mediated hematopoietic injury process. The expression of the above molecules in the benzene exposure population was also examined and consistent with animal experiments. In conclusion, targeting IGF2BP1 alleviated hematopoietic injury caused by benzene exposure, possibly due to the reprogramming of BCAA metabolism and fatty acid oxidation via BCAT1 and CPT1A metabolic enzymes. IGF2BP1 is a potential regulatory and therapeutic target for benzene hematotoxicity.
研究领域:
毒理学
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血液学
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分子生物学
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代谢组学
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转录组学
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PubMed
高影响因子
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