Experimental cell research最新文献

Role of CIRP in glioma Progression: Inhibition of ferroptosis via UBR5-Mediated ACSL4 degradation CIRP在胶质瘤进展中的作用：通过ubr5介导的ACSL4降解抑制铁下垂。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-04-15 Epub Date: 2026-02-12 DOI: 10.1016/j.yexcr.2026.114942

Zhiyin Pang , Xingwang Zu , Ying Yang , Pingping Yan , Huicong Wang , Junjie Liu , Jinmin Hao

Glioma represents the most aggressive form of primary brain tumor, characterized by restricted therapeutic strategies and unfavorable survival rates. Accumulating studies indicate that ferroptosis is critically involved in the advancement of glioma. Although cold-inducible RNA-binding protein (CIRP), an RNA chaperone protein, upregulated in various malignancies, has not been thoroughly investigated in glioma. This research revealed that CIRP is a significantly upregulated gene in glioma patients, with high expression correlating with worse prognosis. Through functional experiments, we demonstrated that CIRP enhances proliferative, migratory, and invasive capacities of glioma cells. Notably, we discovered that CIRP enhanced GBM cell resistance to ferroptosis, as evidenced by reduced intracellular iron levels, decreased lipid peroxidation, and elevated antioxidant capacity. Mechanistic studies revealed that CIRP facilitated the interaction between the E3 ubiquitin ligase UBR5 and ACSL4, leading to increased ubiquitination and subsequent proteasomal degradation of ACSL4. In summary, our findings indicate that CIRP advances glioma progression via inhibiting ferroptosis through the promotion of UBR5-mediated ACSL4 degradation.

胶质瘤是最具侵袭性的原发性脑肿瘤，其特点是治疗策略有限，生存率低。越来越多的研究表明，铁下垂在胶质瘤的进展中起关键作用。尽管冷诱导RNA结合蛋白（CIRP）是一种RNA伴侣蛋白，在各种恶性肿瘤中上调，但尚未在胶质瘤中进行彻底的研究。本研究显示CIRP在胶质瘤患者中是一个显著上调的基因，其高表达与预后不良相关。通过功能实验，我们证明了CIRP增强胶质瘤细胞的增殖、迁移和侵袭能力。值得注意的是，我们发现CIRP增强了GBM细胞对铁下垂的抵抗力，这可以通过降低细胞内铁水平、减少脂质过氧化和提高抗氧化能力来证明。机制研究表明，CIRP促进E3泛素连接酶UBR5和ACSL4之间的相互作用，导致泛素化增加和随后的ACSL4蛋白酶体降解。总之，我们的研究结果表明，CIRP通过促进ubr5介导的ACSL4降解来抑制铁下垂，从而促进胶质瘤的进展。

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引用次数: 0

Temporal modulation of cuproptosis and autophagy mediates nanographene-driven pulmonary fibrosis progression 铜增生和自噬的时间调节介导纳米石墨烯驱动的肺纤维化进展

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-04-01 Epub Date: 2026-02-04 DOI: 10.1016/j.yexcr.2026.114927

Jiarui Xia , Xiaolong Tang , Huijie Shang , Youliang Zhao , Shuqi Li , Ke Tang , Yi Li , Wenzhuo Wu , Qun Xu , Changfu Hao , Wu Yao

Graphene nanoparticles are increasingly used in materials manufacturing, pollutant treatment, energy storage, and electronic devices, and the potential risk of occupational and environmental exposure is a concern. The mechanisms of lung fibrosis induced by nano-graphene with different properties are complex. In addition, multiple modes of programmed cell death (PCD) occur during lung fibrosis, and whether cuproptosis and autophagy exert regulatory effects during the progression of lung fibrosis induced by nano-graphene remains undocumented. In this study, we constructed mouse models with varying doses of graphene and exposure durations. We observed the dynamics of pathological changes in lung histology and the time-series expression of biomarkers. We discovered that graphene could deposit in lung tissue, leading to the pathological manifestations of pulmonary fibrosis; this was coincident with elevated copper ion concentration, cellular cuproptosis, and excessive autophagy. In short, our results may contribute to further elucidation of the potential respiratory toxic effects and mechanisms of graphene, and to the early development of targeted preventive and control measures by providing new ideas and reference points.

石墨烯纳米颗粒越来越多地用于材料制造、污染物处理、能源储存和电子设备，其潜在的职业和环境暴露风险令人担忧。不同性质纳米石墨烯诱导肺纤维化的机制复杂。此外，肺纤维化过程中会发生多种模式的程序性细胞死亡（PCD），纳米石墨烯诱导的肺纤维化过程中铜增生和自噬是否发挥调节作用尚不清楚。在这项研究中，我们构建了具有不同剂量石墨烯和暴露时间的小鼠模型。我们观察了肺组织病理变化的动态和生物标志物的时间序列表达。我们发现石墨烯可以在肺组织中沉积，导致肺纤维化的病理表现；这与铜离子浓度升高、细胞铜增生和过度自噬一致。总之，我们的研究结果可能有助于进一步阐明石墨烯潜在的呼吸毒性作用和机制，并通过提供新的思路和参考点，有助于早期制定有针对性的预防和控制措施。

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引用次数: 0

Insulin-like growth factor-1 enhances β-amyloid protein clearance in HMC3 microglia via low-density lipoprotein receptor-related protein 1-mediated pathway 胰岛素样生长因子-1通过低密度脂蛋白受体相关蛋白1介导的途径增强HMC3小胶质细胞中β-淀粉样蛋白的清除

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI: 10.1016/j.yexcr.2026.114920

Hongsong Guo, Xiaoqian Peng, Xiao Zhang, John Bosco Ruganzu, Xiangyuan Wu, Mingtao Zhao, Pengbo Yang, Shengfeng Ji, Weina Yang

β-amyloid protein (Aβ) deposition occurs years before cognitive symptoms appear and is considered one of the main causes underlying the pathogenic events that occur in Alzheimer's disease (AD). Mounting evidence suggests that the imbalance of Aβ production and clearance leads to the accumulation of Aβ and the subsequent formation of toxic Aβ aggregates. Aβ is internalized by microglia and transported to lysosomes for degradation, which is one of the main ways by which Aβ may be cleared from the brain. Insulin-like growth factor-1 (IGF-1) promotes clearance of Aβ in the brain by enhancing Aβ carrier proteins. Our previous study demonstrated that low-density lipoprotein receptor-related protein 1 (LRP1) mediates the internalization of Aβ_1-42 and lysosomal trafficking in primary cortical neurons. However, whether IGF-1 enhances the clearance of Aβ in microglia through the LRP1-mediated pathway and its underlying mechanisms is incompletely understood. Here, we reported that knockdown of LRP1 expression significantly decreased the internalization of Aβ_1-42 in HMC3 cells. Furthermore, pretreatment with IGF-1 significantly increased intracellular Aβ_1-42, indicating IGF-1 enhances HMC3 cells uptake of extracellular Aβ_1-42. Interestingly, the intracellular Aβ_1-42 in LRP1-knockdown HMC3 cells was reduced after preincubation with IGF-1. Thus, it was indicated that LRP1 is essential for IGF-1-enhanced internalization of Aβ_1-42 in HMC3 cells. Moreover, IGF-1 significantly inhibited the downregulation of PI3K, phospho-PI3K, Akt, and phospho-Akt induced by Aβ_1-42. Importantly, treatment with LY294002, a PI3K inhibitor, significantly reduced the intracellular Aβ_1-42 levels and decreased the expression of LRP1. These findings indicated that IGF-1 enhances the internalization of Aβ in a LRP1-dependent manner by activating the PI3K/Akt signaling pathway. Finally, we identified that IGF-1 promotes lysosomal proteolysis of Aβ_1-42 by increasing cathepsin B (CTSB) and cathepsin D (CTSD) expression. Consequently, these results demonstrated that IGF-1 promotes the internalization and lysosomal degradation of Aβ by microglia, which is an effective approach to lowering brain Aβ levels, and it might be a promising therapeutic target for AD.

β-淀粉样蛋白（Aβ）沉积发生在认知症状出现前数年，被认为是阿尔茨海默病（AD）发病事件的主要原因之一。越来越多的证据表明，Aβ产生和清除的不平衡导致Aβ的积累和随后形成有毒的Aβ聚集体。Aβ被小胶质细胞内化并转运到溶酶体进行降解，这是Aβ从大脑中清除的主要途径之一。胰岛素样生长因子-1 （IGF-1）通过增强Aβ载体蛋白来促进大脑中Aβ的清除。我们之前的研究表明，低密度脂蛋白受体相关蛋白1 （LRP1）介导初级皮质神经元中Aβ1-42的内化和溶酶体的转运。然而，IGF-1是否通过lrp1介导的途径增强小胶质细胞中Aβ的清除及其潜在机制尚不完全清楚。在这里，我们报道了LRP1表达的下调显著降低了a - β1-42在HMC3细胞中的内化。此外，IGF-1预处理显著增加细胞内Aβ1-42，表明IGF-1增强了HMC3细胞对细胞外Aβ1-42的摄取。有趣的是，在lrp1敲除的HMC3细胞中，细胞内a - β1-42在IGF-1预孵生后减少。因此，研究表明LRP1对HMC3细胞中igf -1增强的Aβ1-42内化至关重要。此外，IGF-1显著抑制Aβ1-42诱导的PI3K、phospho-PI3K、Akt和phospho-Akt的下调。重要的是，使用PI3K抑制剂LY294002治疗可显著降低细胞内a - β1-42水平，并降低LRP1的表达。这些发现表明，IGF-1通过激活PI3K/Akt信号通路，以lrp1依赖的方式增强a β的内化。最后，我们发现IGF-1通过增加组织蛋白酶B （CTSB）和组织蛋白酶D （CTSD）的表达来促进Aβ1-42的溶酶体蛋白水解。因此，这些结果表明，IGF-1促进了小胶质细胞对a β的内化和溶酶体降解，这是降低脑内a β水平的有效途径，可能是治疗AD的一个有希望的靶点。

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引用次数: 0

Metabolic Cell Biology - Do. Or do not. There is no try. 代谢细胞生物学-做。或者不要。没有尝试。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-03-21 DOI: 10.1016/j.yexcr.2026.114989

Ji-Long Liu

引用次数: 0

Age-Dependent Decline in Plasmalogen Biosynthesis Impairs Stress-Induced Mitochondrial Fission in Drosophila. 年龄依赖性的等离子原生物合成下降损害应激诱导的果蝇线粒体裂变。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-03-20 DOI: 10.1016/j.yexcr.2026.114974

Ankur Kumar, Anurag Das, Tracey Stewart, Fong-Fu Hsu, Ping Kang, Hua Bai

Mitochondrial dynamics, maintained by balanced fission and fusion, are essential for organelle quality control and cellular homeostasis, yet this process becomes disrupted during aging. The upstream cues underlying age-associated fission defects remain poorly defined. Here, using Drosophila oenocytes (hepatocyte-like cells), we show that aging drives progressive mitochondrial enlargement and morphological abnormalities. Live-cell imaging analysis demonstrated that young oenocytes rapidly undergo mitochondrial fission in response to paraquat-induced oxidative stress, whereas aged oenocytes fail to fragment, resulting in persistently enlarged mitochondria. This age-dependent fission defect correlates with a marked decline in mitochondrial plasmalogen levels, a class of ether phospholipids enriched in mitochondrial membranes. In addition, genetic disruption of plasmalogen biosynthesis using a hypomorphic mutation in the plasmanylethanolamine desaturase Kua (TMEM189) recapitulated the aging phenotype. These findings establish that an age-dependent decline in plasmalogen biosynthesis impairs mitochondrial fission, leading to persistent mitochondrial enlargement. Thus, loss of plasmalogen-dependent membrane dynamics represents a novel mechanism driving mitochondrial dysfunction during aging in metabolic tissues.

线粒体动力学是由平衡的裂变和融合维持的，对于细胞器质量控制和细胞稳态至关重要，但这一过程在衰老过程中被破坏。与年龄相关的裂变缺陷的上游线索仍不明确。在这里，使用果蝇的卵泡细胞（肝细胞样细胞），我们发现衰老驱动进行性线粒体增大和形态异常。活细胞成像分析表明，年轻的卵泡细胞在百草枯诱导的氧化应激下迅速发生线粒体分裂，而年老的卵泡细胞则无法分裂，导致线粒体持续扩大。这种年龄依赖性的裂变缺陷与线粒体质浆原水平的显著下降有关，质浆原是线粒体膜中富集的一类醚磷脂。此外，利用plasmanylethanolamine desaturase Kua （TMEM189）的亚形态突变对plasmalogen生物合成的遗传破坏再现了衰老表型。这些发现表明，年龄依赖性的浆磷脂原生物合成下降会损害线粒体裂变，导致线粒体持续增大。因此，在代谢组织衰老过程中，依赖质原的膜动力学的丧失代表了一种驱动线粒体功能障碍的新机制。

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引用次数: 0

ZFP36 and CEBPA are macrophage-associated prognostic biomarkers linked to glomerular endothelial inflammation in ANCA-associated glomerulonephritis. ZFP36和CEBPA是巨噬细胞相关的预后生物标志物，与anca相关性肾小球肾炎的肾小球内皮炎症有关。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-03-20 DOI: 10.1016/j.yexcr.2026.114988

Anqi Ni, Xinqi Zhu, Junni Wang, Liangliang Chen, Huanhuan Zhu, Jin Miao, Jianhang Xu, Pingping Ren, Jianghua Chen, Liang Xiao, Fei Han

Background: Macrophages are critical in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). This study investigated macrophage-associated genes (MAGs) ZFP36 and CEBPA in AAGN renal tissue and evaluated their role in glomerular endothelial injury.

Methods: Macrophage infiltration and its association with prognosis were assessed in renal tissues via immunohistochemistry. ZFP36 and CEBPA were identified via the Gene Expression Omnibus (GEO) database. Their expression in AAGN and correlation with immune cell infiltration and clinical indicators were analyzed. Serum from healthy individuals and AAGN patients was used to stimulate human renal glomerular endothelial cells (HRGECs), and ZFP36 and CEBPA expression was measured using western blotting and real-time PCR. Functional studies included gene knockdown and overexpression, actinomycin D chase assays, NF-κB inhibition, and a direct co-culture system with THP-1-derived macrophages.

Results: AAGN renal tissues showed marked immune infiltration and macrophage activation, predicting poor prognosis. ZFP36 was downregulated and correlated with poor prognosis, while CEBPA was upregulated and correlated with poor prognosis. Immunofluorescence demonstrated partial localization of both proteins in CD31-positive glomerular endothelial areas. In HRGECs, ZFP36 attenuated inflammatory responses, accelerated TNF-α and IL6 mRNA decay, and was associated with reduced NF-κB activation, whereas CEBPA promoted endothelial inflammatory mediator expression. In co-culture experiments, endothelial ZFP36 reduced, whereas endothelial CEBPA increased, TNF-α production in adjacent macrophages.

Conclusions: ZFP36 and CEBPA are macrophage-associated genes linked to immune infiltration, renal prognosis, and endothelial inflammatory responses in AAGN, and may serve as potential tissue biomarkers and therapeutic targets.

背景：巨噬细胞在抗中性粒细胞胞浆抗体（ANCA）相关性肾小球肾炎（AAGN）中起关键作用。本研究研究了AAGN肾组织中巨噬细胞相关基因（MAGs） ZFP36和CEBPA，并评估了它们在肾小球内皮损伤中的作用。方法：采用免疫组化方法观察肾组织巨噬细胞浸润情况及其与预后的关系。ZFP36和CEBPA通过Gene Expression Omnibus （GEO）数据库进行鉴定。分析其在AAGN中的表达，与免疫细胞浸润及临床指标的相关性。采用健康个体和AAGN患者血清刺激人肾小球内皮细胞（HRGECs），采用western blotting和real-time PCR检测ZFP36和CEBPA的表达。功能研究包括基因敲除和过表达、放线菌素D追踪试验、NF-κB抑制以及与thp -1来源的巨噬细胞直接共培养系统。结果：AAGN肾组织有明显的免疫浸润和巨噬细胞活化，预后较差。ZFP36下调与预后不良相关，CEBPA上调与预后不良相关。免疫荧光显示这两种蛋白部分定位于cd31阳性的肾小球内皮区域。在hrgec中，ZFP36减轻炎症反应，加速TNF-α和IL6 mRNA的衰变，并与NF-κB活化降低相关，而CEBPA促进内皮炎症介质的表达。在共培养实验中，内皮细胞ZFP36减少，内皮细胞CEBPA增加，邻近巨噬细胞产生TNF-α。结论：ZFP36和CEBPA是巨噬细胞相关基因，与AAGN的免疫浸润、肾脏预后和内皮炎症反应有关，可能是潜在的组织生物标志物和治疗靶点。

{"title":"ZFP36 and CEBPA are macrophage-associated prognostic biomarkers linked to glomerular endothelial inflammation in ANCA-associated glomerulonephritis.","authors":"Anqi Ni, Xinqi Zhu, Junni Wang, Liangliang Chen, Huanhuan Zhu, Jin Miao, Jianhang Xu, Pingping Ren, Jianghua Chen, Liang Xiao, Fei Han","doi":"10.1016/j.yexcr.2026.114988","DOIUrl":"https://doi.org/10.1016/j.yexcr.2026.114988","url":null,"abstract":"<p><strong>Background: </strong>Macrophages are critical in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). This study investigated macrophage-associated genes (MAGs) ZFP36 and CEBPA in AAGN renal tissue and evaluated their role in glomerular endothelial injury.</p><p><strong>Methods: </strong>Macrophage infiltration and its association with prognosis were assessed in renal tissues via immunohistochemistry. ZFP36 and CEBPA were identified via the Gene Expression Omnibus (GEO) database. Their expression in AAGN and correlation with immune cell infiltration and clinical indicators were analyzed. Serum from healthy individuals and AAGN patients was used to stimulate human renal glomerular endothelial cells (HRGECs), and ZFP36 and CEBPA expression was measured using western blotting and real-time PCR. Functional studies included gene knockdown and overexpression, actinomycin D chase assays, NF-κB inhibition, and a direct co-culture system with THP-1-derived macrophages.</p><p><strong>Results: </strong>AAGN renal tissues showed marked immune infiltration and macrophage activation, predicting poor prognosis. ZFP36 was downregulated and correlated with poor prognosis, while CEBPA was upregulated and correlated with poor prognosis. Immunofluorescence demonstrated partial localization of both proteins in CD31-positive glomerular endothelial areas. In HRGECs, ZFP36 attenuated inflammatory responses, accelerated TNF-α and IL6 mRNA decay, and was associated with reduced NF-κB activation, whereas CEBPA promoted endothelial inflammatory mediator expression. In co-culture experiments, endothelial ZFP36 reduced, whereas endothelial CEBPA increased, TNF-α production in adjacent macrophages.</p><p><strong>Conclusions: </strong>ZFP36 and CEBPA are macrophage-associated genes linked to immune infiltration, renal prognosis, and endothelial inflammatory responses in AAGN, and may serve as potential tissue biomarkers and therapeutic targets.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114988"},"PeriodicalIF":3.5,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The cGAS-STING signaling pathway mediates pyroptosis in colonic epithelial cells and accelerates the progression of CAC. cGAS-STING信号通路介导结肠上皮细胞焦亡，加速CAC的进展。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-03-19 DOI: 10.1016/j.yexcr.2026.114987

Jian Wang, Anqing Luo, Yizhou Yao, Anning Liu, Xinguo Zhu

Objective: Colitis-associated cancer (CAC) is a minor subtype of CRC, accounting for 2% of CRC cases. It is also one of the most common and severe complications in patients with chronic IBD. The exact pathogenic mechanisms of CAC remain unclear. Therefore, actively investigating the pathogenesis of CAC and developing novel therapeutic strategies are of great significance for its prevention and treatment.

Methods: The mouse model of UC and CAC was induced using DSS and AOM stimulation. The model was validated through H&E staining, Masson, AB-PAS staining, and ELISA assays. Additionally, the expression levels of key molecules, including cGAS and STING, were examined in model mice using qRT-PCR and immunohistochemistry. Later, based on the mouse CAC model, STING inhibitors and agonists were administered in combination with H&E staining, Masson, AB-PAS staining, and ELISA assays to explore the impact of key molecular expression levels on CAC progression in mice. Finally, in a mouse UC organoid model, STING agonists were used in combination with NLRP3 inhibitor. WB, CCK8, immunofluorescence staining, and intestinal permeability tests were employed to investigate the regulatory mechanisms of pyroptosis in CAC development.

Results: DSS and AOM stimulation successfully induced the mouse UC and CAC model. Key proteins of the cGAS-STING pathway, including cGAS, p65, and IFN-I, were significantly upregulated in the mouse UC and CAC model. The STING agonist SR-717 markedly increased the expression of cGAS-STING pathway-related genes, such as cGAS, STING, p65, and IFN-I, exacerbating pathological features and serum inflammatory cytokine levels in the colonic cancer model. It also significantly upregulated pyroptosis marker proteins caspase-1, GSDMD-N, and NLRP3, whereas the STING inhibitor H-151 effectively suppressed these effects. The NLRP3 inhibitor INF195 enhanced the proliferative capacity, membrane integrity, and intestinal barrier function of the mouse colon organoid model, providing partial protective effects. Meanwhile, the STING agonist SR-717 partially reversed the effects of INF195.

Conclusion: The cGAS-STING signaling pathway accelerates the progression of CAC by promoting pyroptosis in colonic epithelial cells through NLRP3/caspase-1 mediation.

目的：结肠炎相关癌（colitis associated cancer， CAC）是CRC的一个次要亚型，约占CRC病例的2%。它也是慢性IBD患者最常见和最严重的并发症之一。CAC的确切致病机制尚不清楚。因此，积极研究CAC的发病机制，制定新的治疗策略，对预防和治疗CAC具有重要意义。方法：采用DSS和AOM刺激诱导小鼠UC和CAC模型。通过H&E染色、Masson染色、AB-PAS染色和ELISA检测对模型进行验证。此外，采用qRT-PCR和免疫组织化学方法检测模型小鼠cGAS和STING等关键分子的表达水平。随后，以小鼠CAC模型为基础，结合H&E染色、Masson染色、AB-PAS染色和ELISA检测，给予STING抑制剂和激动剂，探讨关键分子表达水平对小鼠CAC进展的影响。最后，在小鼠UC类器官模型中，STING激动剂与NLRP3抑制剂联合使用。采用WB、CCK8、免疫荧光染色和肠通透性试验研究焦亡在CAC发展中的调控机制。结果：DSS和AOM刺激成功诱导小鼠UC和CAC模型。cGAS- sting通路的关键蛋白，包括cGAS、p65和IFN-I，在小鼠UC和CAC模型中显著上调。STING激动剂SR-717显著提高cGAS-STING通路相关基因cGAS、STING、p65、IFN-I的表达，加重了结肠癌模型的病理特征和血清炎症细胞因子水平。它还显著上调了焦亡标记蛋白caspase-1、GSDMD-N和NLRP3，而STING抑制剂H-151有效地抑制了这些作用。NLRP3抑制剂INF195可增强小鼠结肠类器官模型的增殖能力、膜完整性和肠屏障功能，提供部分保护作用。同时，STING激动剂SR-717部分逆转了INF195的作用。结论：cGAS-STING信号通路通过NLRP3/caspase-1介导，促进结肠上皮细胞焦亡，从而加速CAC的进展。

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引用次数: 0

AURKA promotes radioresistance in pancreatic cancer via GSK3β-mediated PTEN phosphorylation at T366. AURKA通过gsk3 β介导的PTEN在T366位点的磷酸化促进胰腺癌的放射耐药。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-03-19 DOI: 10.1016/j.yexcr.2026.114986

Di Chen, Xiaofei Zhu, Jiaojiao Tong, Chengyi Huang, Wenjuan Chen, Bichun Xu, Liang Chen, Chen Ye, Huojun Zhang

Radioresistance is a major therapeutic challenge in clinical management of pancreatic ductal adenocarcinoma (PDAC), yet the molecular mechanisms governing this process remain largely elusive. In this study, it was demonstrated that the oncogenic kinase Aurora Kinase A (AURKA) drove radioresistance by orchestrating a signaling cascade that inhibited the tumor suppressor PTEN. Analysis of patient cohorts and TCGA data revealed that AURKA was overexpressed in PDAC, and its expression levels were found to robustly correlate with poor patient prognosis. Functionally, AURKA overexpression conferred potent radioresistance, yielding SER values of 0.847 ± 0.086 and 0.824 ± 0.073 in PANC-1 and SW1990 cells, respectively. AURKA overexpression not only markedly enhanced cellular proliferation and migration but also significantly suppressed apoptosis. Mechanistically, Co-IP uncovered that AURKA physically interacted with Glycogen Synthase Kinase 3β (GSK3β). This interaction facilitated the inhibitory phosphorylation of the tumor suppressor PTEN at Threonine 366, which impaired PTEN's phosphatase activity and led to sustained activation of the pro-survival PI3K/AKT/mTOR pathway. Critically, this radioresistant phenotype was reversed by either GSK3β knockdown or the expression of a phosphorylation-deficient PTEN-T366A mutant, confirming the essentiality of this signaling axis. Collectively, this study discovered a novel and clinically relevant AURKA-GSK3β-PTEN signaling axis that mechanistically linked AURKA overexpression to radioresistance in PDAC. Furthermore, our findings provide a strong mechanistic rationale for targeting AURKA, revealing a promising therapeutic strategy to overcome radioresistance and improve therapeutic outcomes in pancreatic cancer.

放射耐药是胰腺导管腺癌（PDAC）临床治疗的主要挑战，然而控制这一过程的分子机制在很大程度上仍然难以捉摸。在这项研究中，证明了致癌激酶极光激酶A （AURKA）通过协调抑制肿瘤抑制因子PTEN的信号级联来驱动辐射抗性。对患者队列和TCGA数据的分析显示，AURKA在PDAC中过表达，其表达水平与患者预后不良密切相关。在功能上，AURKA过表达赋予了有效的辐射抗性，PANC-1和SW1990细胞的SER值分别为0.847±0.086和0.824±0.073。AURKA过表达不仅能显著促进细胞增殖和迁移，还能显著抑制细胞凋亡。在机制上，Co-IP发现AURKA与糖原合成酶激酶3β (GSK3β)相互作用。这种相互作用促进了肿瘤抑制因子PTEN在苏氨酸366处的抑制性磷酸化，从而损害了PTEN的磷酸酶活性，并导致促生存PI3K/AKT/mTOR通路的持续激活。关键的是，GSK3β敲低或磷酸化缺陷PTEN-T366A突变体的表达可以逆转这种辐射抗性表型，从而证实了该信号轴的重要性。总的来说，这项研究发现了一个新的和临床相关的AURKA- gsk3 β- pten信号轴，该信号轴将AURKA过表达与PDAC的放射耐药机制联系起来。此外，我们的研究结果为靶向AURKA提供了强有力的机制基础，揭示了一种有希望的治疗策略，可以克服胰腺癌的放射耐药并改善治疗结果。

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引用次数: 0

AHNAK inhibits osteoporosis progression by stabilizing Smad1 protein AHNAK通过稳定Smad1蛋白抑制骨质疏松症进展。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-03-15 Epub Date: 2026-01-17 DOI: 10.1016/j.yexcr.2026.114899

Weifei Zhang , Hua Chen , Tiantian Qi , Dengbo Yao , Hang Liu , Hui Zeng , Fei Yu , Wenyu Zhou

AHNAK is a structural scaffold protein implicated in a wide array of physiological functions. AHNAK mutations are highly prevalent in patients with osteoporosis, However, it is currently unknown whether AHNAK affects the progression of osteoporosis and the specific mechanism behind this effect. This study detected decreased AHNAK (AHNAK1) expression in bone tissues and bone marrow mesenchymal stem cells (BMSCs) of osteoporotic mice. Genetic knockdown of AHNAK inhibited osteogenic differentiation of BMSCs. Mechanistic investigations indicated that AHNAK functions through stabilizing Smad1 protein levels. Overexpression of Smad1 in AHNAK-knockdown BMSCs restored their osteogenic differentiation capacity. Furthermore, in vivo mouse experiments further confirmed these findings. Collectively, these findings indicate that AHNAK inhibits the progression of osteoporosis by stabilizing Smad1 protein.

AHNAK是一种结构支架蛋白，涉及广泛的生理功能。AHNAK突变在骨质疏松症患者中非常普遍，然而，目前尚不清楚AHNAK是否影响骨质疏松症的进展以及这种影响背后的具体机制。本研究检测到骨质疏松小鼠骨组织和骨髓间充质干细胞（BMSCs）中AHNAK （AHNAK1）表达降低。基因敲低AHNAK抑制骨髓间充质干细胞成骨分化。机制研究表明AHNAK通过稳定Smad1蛋白水平发挥作用。在ahnak缺失的骨髓间充质干细胞中，Smad1的过表达恢复了它们的成骨分化能力。此外，小鼠体内实验进一步证实了这些发现。总的来说，这些发现表明AHNAK通过稳定Smad1蛋白来抑制骨质疏松症的进展。

引用次数: 0

The Runx2 switch: unlocking osteoblast-related disorders through signaling pathways and non-coding RNAs Runx2开关：通过信号通路和非编码rna解锁成骨细胞相关疾病

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-03-15 Epub Date: 2026-01-30 DOI: 10.1016/j.yexcr.2026.114921

Somayeh Aslani , Ashkan Kalantary-Charvadeh , Roghayeh Abbasalipourkabir , Nasrin Ziamajidi

Osteoblasts, specialized bone-forming cells, differentiate from mesenchymal stem cells (MSCs). In recent years, stem cell-derived osteoblasts have emerged as potential choices for the treatment of bone-related disorders. A complex network of regulatory elements, including signaling pathways, transcription factors, and non-coding RNAs (ncRNAs), orchestrates MSCs differentiation. Among the key regulators of osteoblast differentiation is Runt-related transcription factor 2 (Runx2), a master transcription factor essential for osteogenic commitment. Elucidating the molecular mechanisms that regulate Runx2 expression and function is critical for the treatment of osteoblast-related disease. Runx2 is regulated through signaling pathways and a complex, post-transcriptional competing endogenous RNA (ceRNA) network. In this network, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) sequester microRNAs (miRNAs), thereby fine-tuning Runx2 expression. Signaling pathways can also indirectly regulate Runx2 by inducing the expression of osteo-regulatory miRNAs. This review highlights the regulatory role of Runx2 during osteoblastic differentiation. It also explores how signaling pathways, lncRNAs, circRNAs, and other factors interact with Runx2-regulatory miRNAs involved in this process.

成骨细胞是由间充质干细胞（MSCs）分化而来的特化骨形成细胞。近年来，干细胞衍生成骨细胞已成为治疗骨相关疾病的潜在选择。一个复杂的调控元件网络，包括信号通路、转录因子和非编码rna (ncRNAs)，协调MSCs的分化。成骨细胞分化的关键调控因子之一是runt相关转录因子2 (Runx2)，这是成骨承诺所必需的主要转录因子。阐明调控Runx2表达和功能的分子机制对于治疗成骨细胞相关疾病至关重要。Runx2通过信号通路和复杂的转录后竞争内源性RNA （ceRNA）网络进行调节。在这个网络中，环状rna （circRNAs）和长链非编码rna （lncRNAs）隔离microRNAs (miRNAs)，从而微调Runx2的表达。信号通路也可以通过诱导骨调控mirna的表达间接调控Runx2。本文综述了Runx2在成骨细胞分化过程中的调控作用。它还探讨了信号通路、lncrna、circrna和其他因子如何与参与该过程的runx2调节mirna相互作用。

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引用次数: 0