Experimental cell research最新文献_第4页

Knockdown of PELI1 promotes Th2 and Treg cell differentiation in juvenile idiopathic arthritis 敲低PELI1可促进幼年特发性关节炎中Th2和Treg细胞的分化。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114360

Dan Li , Xiaoqing Li , Mingyue Duan , Xiuhong Xue , Xianyan Tang , Nan Nan , Rui Zhao , Wenhua Zhang , Wanggang Zhang

Pellino1 (PELI1) is a key regulator of inflammatory and autoimmune diseases. The role of PELI1 in juvenile idiopathic arthritis (JIA) is unclear. The correlation between serum PELI1 mRNA levels and clinical indicators of JIA patients was evaluated by Pearson correlation analysis. The percentage of Th1, Th2, Th17 and Treg cells was analyzed by flow cytometry. ELISA kits were used to detect cytokine levels in serum and cell supernatants. Co-immunoprecipitation experiments were performed to validate PELI1 and TCF-1 interactions. The protein and ubiquitination levels of TCF-1 were detected by western blot. The results showed that JIA patients have high serum PELI1 levels. PELI1 levels were positively correlated with erythrocyte sedimentation rate, C-reactive protein levels and JADAS27 scores in JIA patients. Interfering with PELI1 promoted naïve CD4⁺ T cell differentiation to Th2 and Treg cells and increased IL-4 and IL-10 levels, while inhibiting their differentiation to Th1 and Th17 cells and decreasing IFN-γ and IL-17 levels. PELI1 increased TCF-1 ubiquitination levels and accelerated its degradation. Inhibition of TCF-1 reduced the effects of interfering with PELI1 on cell differentiation and cytokine levels. In conclusion, Silencing of PELI1 facilitated the naïve CD4⁺ T cell differentiation into Th2 and Treg cells by TCF-1.

Pellino1 （PELI1）是炎症和自身免疫性疾病的关键调节因子。PELI1在幼年特发性关节炎（JIA）中的作用尚不清楚。采用Pearson相关分析评价JIA患者血清PELI1 mRNA水平与临床指标的相关性。流式细胞术分析Th1、Th2、Th17和Treg细胞的百分比。ELISA试剂盒检测血清和细胞上清液中细胞因子水平。通过共免疫沉淀实验验证PELI1和TCF-1的相互作用。western blot检测TCF-1蛋白和泛素化水平。结果显示JIA患者血清PELI1水平较高。JIA患者PELI1水平与红细胞沉降率、c反应蛋白水平及JADAS27评分呈正相关。干扰PELI1可促进naïve CD4+ T细胞向Th2和Treg细胞分化，提高IL-4和IL-10水平，抑制其向Th1和Th17细胞分化，降低IFN-γ和IL-17水平。PELI1增加TCF-1泛素化水平，加速其降解。抑制TCF-1可降低干扰PELI1对细胞分化和细胞因子水平的影响。综上所述，pili1的沉默促进了TCF-1介导naïve CD4+ T细胞向Th2和Treg细胞的分化。

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引用次数: 0

ALDH2 plays a role in spermatogenesis and male fertility by regulating oxidative stress in mice ALDH2通过调节小鼠氧化应激在精子发生和雄性生育中发挥作用。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114397

Ying Lv , Xing Yang , Xiaoli Sun , Linxiao Lv , Zexin Zhang , Chenyang Li , Jiangang Gao , Huatao Li , Zongzhuang Wen , Haixia Zhu

Spermatogenesis and sperm maturation are complex biological processes that involve intricate cellular and molecular interactions. The Aldh2 gene is involved in the metabolism of specific aldehydes generated by oxidative stress. Aldh2 is abundantly expressed in the testis and epididymis; however, the specific role of Aldh2 in regulating spermatogenesis and sperm maturation remains unclear. In the present study, we generated Aldh2 knockout (Aldh2^−/−) mice by using CRISPR/Cas9 technology. Aldh2 gene knockout decreased the fertility of male mice. Compared to the control group mice, Aldh2^−/− mice showed a significant decrease in the thickness of the seminiferous tubules and the number of germ cells. Further investigation revealed that the meiosis of spermatocytes and acrosome formation in sperm were disrupted in Aldh2^−/− mice, leading to oligoasthenoteratozoospermia in male mice. However, the caput epididymis and cauda epididymis in Aldh2^−/− mice showed identical proportions of morphologically abnormal sperm. Mechanistically, 4-hydroxynonenal, 3-nitro-L-tyrosine, and malondialdehyde levels were significantly elevated in both the testis and epididymis of Aldh2^−/− mice, thus indicating increased oxidative stress in the reproductive system. Collectively, our findings demonstrate that Aldh2 plays a critical role in spermatogenesis by regulating oxidative stress in mice.

精子发生和精子成熟是复杂的生物学过程，涉及复杂的细胞和分子相互作用。Aldh2基因参与氧化应激产生的特定醛的代谢。Aldh2在睾丸和附睾中大量表达；然而，Aldh2在调节精子发生和精子成熟中的具体作用尚不清楚。在本研究中，我们利用CRISPR/Cas9技术产生了Aldh2敲除（Aldh2-/-）小鼠。敲除Aldh2基因降低了雄性小鼠的生育能力。与对照组小鼠相比，Aldh2-/-小鼠的精小管厚度和生殖细胞数量明显减少。进一步研究发现，Aldh2-/-小鼠的精母细胞减数分裂和精子顶体形成被破坏，导致雄性小鼠出现少弱异卵精子症。然而，在Aldh2-/-小鼠的附睾头和附睾尾显示相同比例的形态异常精子。机制上，Aldh2-/-小鼠睾丸和附睾中4-羟基壬烯醛、3-硝基- l -酪氨酸和丙二醛水平均显著升高，表明生殖系统氧化应激增加。总的来说，我们的研究结果表明，Aldh2通过调节小鼠的氧化应激在精子发生中起着关键作用。

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引用次数: 0

Ku70 targets BRD3-MYC/Cyclin D1 axis to drive hepatocellular carcinoma progression Ku70靶向BRD3-MYC/Cyclin D1轴驱动肝细胞癌进展

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114404

Wenshuang Sun , Ji Cheng , Ruijun Zhao , Yujie Xiang , Yuting Li , Cuifu Yu , Yuanfei Deng , Gengxi Cai , Hongbiao Huang , Qiucheng Lei , Yuning Liao , Qing Liu

Hepatocellular carcinoma (HCC) is a common cancer characterized by robustly proliferative and metastatic capabilities. Bromodomain-containing proteins are critical to the development of diverse diseases via regulating cell proliferation, differentiation, and death. However, the role of Bromodomain-containing protein 3 (BRD3) in HCC is elusive. Here, we found that BRD3 is notably upregulated in HCC samples and promotes the proliferation of HCC cells. Depletion of BRD3 notably inhibits the expression of c-MYC and Cyclin D1 and abrogates cell cycle progression in HCC cells. Co-IP and biomass spectrometry found that Ku70 interacts with BRD3 in the nucleus. The Ku70-BRD3 complex increases the expression of Cyclin D1 and c-MYC at transcriptional level in HCC. Additionally, depletion of Ku70/BRD3 ameliorates the growth of HCC xenografts established in mice. More importantly, the expression of Ku70 or BRD3 is positively correlated with the protein expression of c-MYC and Cyclin D1 in HCC samples. High expression of BRD3 or Ku70 is closely associated with poor prognosis in HCC patients. Overall, we reveal the important role of the Ku70-BRD3 complex in the onset and progression of HCC, suggesting that the Ku70-BRD3 complex is a promising target for clinical intervention in HCC.

肝细胞癌（HCC）是一种常见的癌症，其特点是具有强大的增殖和转移能力。含溴结构域的蛋白通过调节细胞增殖、分化和死亡对多种疾病的发生至关重要。然而，含溴结构域蛋白3 （BRD3）在HCC中的作用尚不明确。在这里，我们发现BRD3在HCC样本中明显上调，并促进HCC细胞的增殖。BRD3的缺失显著抑制了HCC细胞中c-MYC和Cyclin D1的表达，并抑制了细胞周期的进展。Co-IP和生物质光谱分析发现，Ku70在细胞核中与BRD3相互作用。在HCC中，Ku70-BRD3复合物在转录水平上增加Cyclin D1和c-MYC的表达。此外，Ku70/BRD3的缺失可改善小鼠肝癌异种移植物的生长。更重要的是，在HCC样本中，Ku70或BRD3的表达与c-MYC和Cyclin D1的蛋白表达呈正相关。BRD3或Ku70的高表达与HCC患者预后不良密切相关。总之，我们揭示了Ku70-BRD3复合物在HCC发生和发展中的重要作用，提示Ku70-BRD3复合物是HCC临床干预的一个有希望的靶点。

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引用次数: 0

The Ku protein family regulates hyperglycemia-induced vascular endothelial cell inflammation by modulating P300 levels Ku蛋白家族通过调节P300水平调控高血糖诱导的血管内皮细胞炎症。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114399

Qinqin Cai , Qiao Zhao , Qingxia Yang , Min Zhu , Fufen Meng , Jihong Jiang

Endothelial inflammation caused by hyperglycemia contributes to cardiovascular complications in patients with diabetes. Diabetic kidney injury (DKI) is one of the most significant manifestations of diabetes-related renal damage, encompassing both acute and early chronic kidney injury. DKI involves pathological mechanisms linked to inflammatory responses and early renal damage, which, if left unchecked, may progress to diabetic kidney disease. Previous research indicates that both P300 and Ese-1 play pivotal roles in hyperglycemia-induced endothelial inflammation. This study suggests that P300 modulates Ese-1 expression, promoting hyperglycemia-mediated vascular endothelial inflammation and thereby contributing to the occurrence and progression of DKI. Our findings revealed increased levels of tumor necrosis factor α (Tnf-α), p65 phosphorylation, and monocyte chemotactic proteins Mip-1β and Mip-2 in the kidney tissues of diabetic mice and hyperglycemic human renal glomerular microvascular endothelial cells (HRGECs). Additionally, hyperglycemia orchestrated endothelial inflammation through the upregulation of Ese-1 expression in vitro. Furthermore, P300 was found to be upregulated both in vitro and in vivo. Moreover, silencing P300 reduced hyperglycemia-induced inflammatory effects, which could be reversed by overexpressing Ese-1 in HRGECs. Further, P300 was observed to interact with the Ku protein family (Ku70/Ku86), which were downregulated in the kidney tissues of diabetic mice and hyperglycemic HRGECs. siKu70 and siKu86 intensified hyperglycemia-induced endothelial inflammation, an effect counteracted by P300 silencing. In essence, the Ku protein family interacts with P300 to modulate Ese-1 expression in HRGECs, thereby participating in hyperglycemia-induced endothelial inflammation.

高血糖引起的内皮炎症是糖尿病患者心血管并发症的重要因素。糖尿病性肾损伤（DKI）是糖尿病相关性肾损害最重要的表现之一，包括急性和早期慢性肾损伤。DKI涉及与炎症反应和早期肾损害相关的病理机制，如果不加以控制，可能发展为糖尿病肾病。先前的研究表明P300和Ese-1在高血糖诱导的内皮细胞炎症中起关键作用。本研究提示P300调节Ese-1表达，促进高血糖介导的血管内皮炎症，从而参与DKI的发生和进展。我们的研究结果显示，在糖尿病小鼠和高血糖人肾小球微血管内皮细胞（HRGECs）的肾脏组织中，肿瘤坏死因子α (Tnf-α)、p65磷酸化和单核细胞趋化蛋白Mip-1β和Mip-2水平升高。此外，在体外实验中，高血糖通过上调Ese-1表达介导内皮细胞炎症。此外，P300在体内和体外均上调。此外，沉默P300可以降低高血糖诱导的炎症效应，这可以通过在hrgec中过表达Ese-1来逆转。此外，P300被观察到与Ku蛋白家族（Ku70/Ku86）相互作用，该家族在糖尿病小鼠和高血糖hrgcs的肾脏组织中下调。siKu70和siKu86加剧了高血糖诱导的内皮炎症，P300沉默可以抵消这一作用。本质上，Ku蛋白家族与P300相互作用，调节es1在hrgec中的表达，从而参与高血糖诱导的内皮细胞炎症。

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引用次数: 0

Umbilical cord mesenchymal stem cell-derived exosomal Follistatin inhibits fibrosis and promotes muscle regeneration in mice by influencing Smad2 and AKT signaling 脐带间充质干细胞来源的外泌体Follistatin通过影响Smad2和AKT信号传导抑制小鼠纤维化并促进肌肉再生。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114396

Hai Hu , Yuesong Yin , Hecheng Zhou , Binbin Jiang , Ting Cai , Song Wu , Shuangfei Guo

Background

Promoting muscle regeneration through stem cell therapy has potential risks. We investigated the effect of umbilical cord mesenchymal stem cells (UMSCs) Exosomes (Exo) Follistatin on muscle regeneration.

Methods

The Exo was derived from UMSCs cells and was utilized to affect the mice muscle injury model and C2C12 cells myotubes atrophy model. The Western blot, qRT-PCR and IF were utilized to determine the effects of Exo on the levels of Follistatin, MyHC, MyoD, Myostatin, MuRF1, MAFbx, α-SMA, Collagen I, Smad2, and AKT. In addition, HE and Masson staining were used to assess muscle tissue damage in mice.

Results

The level of Follistatin in Exo was significantly higher than that in UMSCs. UMSCs-Exo increased the levels of Follistatin, MyHC, MyoD, and p-Smad2 and decreased the levels of Myostatin, MuRF1, MAFbx, α-SMA, Collagen I, p-AKT, and p-mTOR in mice or C2C12 cells. In addition, UMSCs-Exo decreased levels of inflammation and fibrosis in mice. However, UMSCs-Exo-si-Follistatin reversed the effect of UMSCs-Exo. Transfection of oe-Smad2 up-regulated the protein levels of Collagen I, α-SMA, and changed the ratio of p-Smad2/Smad2 expression to 0.33, and 0.34, 0.73. LY294002 decreased the levels of MyHC, MyoD, and the ratio of p-AKT/AKT and p-mTOR/mTOR expression to 0.12, 0.17, 0.33, and 0.41, increased the levels of MuRF1 and MAFbx to 0.36 and 0.34.

Conclusion

This study demonstrated that Follistatin in UMSCs-Exo inhibits fibrosis and promotes muscle regeneration in mice by regulating Smad and AKT signaling.

背景：通过干细胞治疗促进肌肉再生具有潜在的风险。我们研究了脐带间充质干细胞（UMSCs）外泌体（Exo）卵泡素对肌肉再生的影响。方法：从UMSCs细胞中提取Exo，应用于小鼠肌肉损伤模型和C2C12细胞肌管萎缩模型。采用western blot、qRT-PCR和IF检测Exo对细胞中Follistatin、MyHC、MyoD、Myostatin、MuRF1、MAFbx、α-SMA、Collagen I、Smad2和AKT水平的影响。此外，采用HE和Masson染色评估小鼠肌肉组织损伤。结果：Exo细胞中Follistatin水平明显高于UMSCs。UMSCs-Exo增加了小鼠或C2C12细胞中Follistatin、MyHC、MyoD和p-Smad2的水平，降低了Myostatin、MuRF1、MAFbx、α-SMA、Collagen I、p-AKT和p-mTOR的水平。此外，UMSCs-Exo降低了小鼠的炎症和纤维化水平。然而，UMSCs-Exo-si- follistatin逆转了UMSCs-Exo的作用。转染e-Smad2可上调α-SMA、I型胶原蛋白的表达水平，p-Smad2/Smad2的表达比分别为0.33、0.34、0.73。LY294002使MyHC、MyoD水平降低，p-AKT/ AKT和p-mTOR/mTOR表达比分别为0.12、0.17、0.33和0.41，MuRF1和MAFbx表达比分别为0.36和0.34。结论：本研究表明UMSCs-Exo中的Follistatin通过调节Smad和AKT信号通路抑制小鼠纤维化，促进肌肉再生。

{"title":"Umbilical cord mesenchymal stem cell-derived exosomal Follistatin inhibits fibrosis and promotes muscle regeneration in mice by influencing Smad2 and AKT signaling","authors":"Hai Hu , Yuesong Yin , Hecheng Zhou , Binbin Jiang , Ting Cai , Song Wu , Shuangfei Guo","doi":"10.1016/j.yexcr.2024.114396","DOIUrl":"10.1016/j.yexcr.2024.114396","url":null,"abstract":"<div><h3>Background</h3><div>Promoting muscle regeneration through stem cell therapy has potential risks. We investigated the effect of umbilical cord mesenchymal stem cells (UMSCs) Exosomes (Exo) Follistatin on muscle regeneration.</div></div><div><h3>Methods</h3><div>The Exo was derived from UMSCs cells and was utilized to affect the mice muscle injury model and C2C12 cells myotubes atrophy model. The Western blot, qRT-PCR and IF were utilized to determine the effects of Exo on the levels of Follistatin, MyHC, MyoD, Myostatin, MuRF1, MAFbx, α-SMA, Collagen I, Smad2, and AKT. In addition, HE and Masson staining were used to assess muscle tissue damage in mice.</div></div><div><h3>Results</h3><div>The level of Follistatin in Exo was significantly higher than that in UMSCs. UMSCs-Exo increased the levels of Follistatin, MyHC, MyoD, and p-Smad2 and decreased the levels of Myostatin, MuRF1, MAFbx, α-SMA, Collagen I, p-AKT, and p-mTOR in mice or C2C12 cells. In addition, UMSCs-Exo decreased levels of inflammation and fibrosis in mice. However, UMSCs-Exo-si-Follistatin reversed the effect of UMSCs-Exo. Transfection of oe-Smad2 up-regulated the protein levels of Collagen I, α-SMA, and changed the ratio of p-Smad2/Smad2 expression to 0.33, and 0.34, 0.73. LY294002 decreased the levels of MyHC, MyoD, and the ratio of p-AKT/AKT and p-mTOR/mTOR expression to 0.12, 0.17, 0.33, and 0.41, increased the levels of MuRF1 and MAFbx to 0.36 and 0.34.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that Follistatin in UMSCs-Exo inhibits fibrosis and promotes muscle regeneration in mice by regulating Smad and AKT signaling.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114396"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893397","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

LINC02987 suppression hepatocellular carcinoma progression by modulating autophagy via the miR-338-3p/ATG12 axis 通过miR-338-3p/ATG12轴调节自噬抑制肝细胞癌进展。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114398

Haiyan Fu , Qiuhong Wang , Haiwen Li , Hongjuan Li , Jie Li , Yu Liu , Futao Dang , Lifeng Wang , Xuan Zhang , Yongrui Yang , Yingrong Du

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is marked by a high mortality rate, with the misregulation of long non-coding RNAs (LncRNAs) playing a key role in its development. Here, we studied the role of LINC02987 in HCC. We employed bioinformatics tools to identify LncRNAs and miRNAs that exhibit differential expression in HCC. Quantitative real-time reverse transcription PCR (RT-qPCR) and Western blot analysis were utilized to quantify gene and protein expression levels. The interaction between miR-338-3p and LINC02987 or ATG12 was confirmed through dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. We observed that LINC02987 was overexpressed in HCC tumor tissues and cell lines. Silencing of LINC02987 led to a reduction in cell viability, diminished clonogenic potential, and attenuated invasive and migratory capabilities. Also, decreasing protein level and fluorescence intensity of the autophagy-associated LC3 I/II. In HCC, miR-338-3p expression was downregulated, while inversely correlates with the overexpression of the autophagy protein ATG12. Mimicking miR-338-3p suppresses the activity of both LINC02987 and ATG12, as evidenced by reduced luciferase signals in corresponding reporter assays. Mimicking miR-338-3p suppresses the activity of both LINC02987 and ATG12, as evidenced by reduced luciferase signals in reporter assays. Transfection with si-LINC02987 decreased ATG12 expression, an effect that was partially reversed by miR-338-3p knockdown. Inhibition of miR-338-3p or overexpression of ATG12 increased LC3 I/II protein levels. Our results indicate that LINC02987 sequesters miR-338-3p, leading to increased ATG12 and promoting autophagy in HCC cells. These results highlight the potential of LINC02987 as a therapeutic target for the treatment of HCC.

肝细胞癌（hepatellular carcinoma， HCC）是最常见的原发性肝癌，其特点是死亡率高，长链非编码rna （long non-coding rna, LncRNAs）的错误调控在其发生发展中起着关键作用。在此，我们研究了LINC02987在HCC中的作用。我们使用生物信息学工具来鉴定在HCC中表现出差异表达的lncrna和mirna。采用实时荧光定量反转录PCR （RT-qPCR）和Western blot分析定量基因和蛋白的表达水平。通过双荧光素酶报告基因和RNA免疫沉淀（RIP）实验证实了miR-338-3p与LINC02987或ATG12之间的相互作用。我们观察到LINC02987在HCC肿瘤组织和细胞系中过表达。沉默LINC02987导致细胞活力降低，克隆潜能减弱，侵袭和迁移能力减弱。同时，自噬相关LC3 I/II蛋白水平和荧光强度降低。在HCC中，miR-338-3p表达下调，而与自噬蛋白ATG12的过表达呈负相关。模拟miR-338-3p抑制LINC02987和ATG12的活性，在相应的报告基因检测中，荧光素酶信号降低证明了这一点。模仿miR-338-3p抑制LINC02987和ATG12的活性，报告基因实验中荧光素酶信号的减少证明了这一点。转染si-LINC02987降低ATG12的表达，这一作用被miR-338-3p敲低部分逆转。抑制miR-338-3p或过表达ATG12可增加LC3 I/II蛋白水平。我们的研究结果表明，LINC02987隔离miR-338-3p，导致HCC细胞中ATG12升高并促进自噬。这些结果突出了LINC02987作为HCC治疗靶点的潜力。

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引用次数: 0

Nucleostemin interacts with SMAD3 promoting tumor metastasis 核干素与SMAD3相互作用促进肿瘤转移。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114362

Xuling Sun , Jiageng He , Yujiang Li , Zhiqiang Chu , Lei Zhu , Hui Zhang , Xiangwei Wu

SMAD3 plays a crucial role in TGF-β, regulating various normal developmental mechanisms and disease pathogenesis. Here, we report that SMAD3 directly interacts with Nucleostemin (NS), leading to nuclear translocation and affecting SMAD3 activity after TGF-β1 stimulation. Moreover, NS acts as a competitor, preventing PPM1A from recognizing and dephosphorylating SMAD3. Experimental investigations have demonstrated that NS significantly enhances cellular migration and invasion by promoting the EMT mechanism in vitro. NS knockdown notably suppresses tumor metastasis in the lungs and liver in vivo. Importantly, NS expression is significantly elevated in numerous human malignancies, correlating with a poorer prognosis. The collective evidence from these studies suggests that NS exhibits oncogenic characteristics, supporting further exploration of NS as a potential target for tumor treatment.

SMAD3在TGF-β中发挥重要作用，调节多种正常发育机制和疾病发病机制。在这里，我们报道SMAD3直接与核干素（NS）相互作用，导致核易位，并在TGF-β1刺激后影响SMAD3的活性。此外，NS作为竞争者，阻止PPM1A识别和去磷酸化SMAD3。实验研究表明，NS通过促进体外EMT机制显著增强细胞迁移和侵袭。NS敲低在体内可显著抑制肿瘤在肺和肝脏的转移。重要的是，NS表达在许多人类恶性肿瘤中显著升高，与较差的预后相关。这些研究的共同证据表明，NS具有致癌特征，支持进一步探索NS作为肿瘤治疗的潜在靶点。

引用次数: 0

RPF2 and CARM1 cooperate to enhance colorectal cancer metastasis via the AKT/GSK-3β signaling pathway RPF2和CARM1通过AKT/GSK-3β信号通路共同促进结直肠癌转移。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114374

Cong Cheng , KeMing Zhang , MaCheng Lu , Yuan Zhang , Tong Wang , Ye Zhang

RPF2 plays a crucial role in promoting epithelial-mesenchymal transition (EMT) and regulating metastasis in colorectal cancer (CRC). By analyzing data from the TCGA and GEO databases, we observed significantly elevated RPF2 expression in CRC, which correlated with EMT markers. Further investigations using stable RPF2 overexpression and knockdown cell lines demonstrated that RPF2 facilitates EMT activation through the AKT/GSK-3β signaling pathway. Notably, CARM1 was identified as a key downstream effector of RPF2. Selective inhibition of CARM1 effectively suppressed the activation of the AKT/GSK-3β pathway and EMT induced by RPF2 overexpression. Both in vitro and in vivo experiments confirmed that RPF2 expression levels positively correlate with the metastatic potential of CRC cells. Moreover, treatment with a CARM1 inhibitor significantly reduced the invasive and migratory capabilities of RPF2-overexpressing cells. These findings suggest that RPF2 drives CRC metastasis by modulating EMT via the AKT/GSK-3β pathway, with CARM1 serving as a critical mediator, offering potential therapeutic targets for CRC.

RPF2在促进结直肠癌（CRC）上皮-间质转化（EMT）和调节转移中起着至关重要的作用。通过分析TCGA和GEO数据库的数据，我们观察到RPF2在CRC中的表达显著升高，其与EMT标志物相关。对稳定的RPF2过表达和敲低细胞系的进一步研究表明，RPF2通过AKT/GSK-3β信号通路促进EMT激活。值得注意的是，CARM1被确定为RPF2的关键下游效应因子。选择性抑制CARM1可有效抑制AKT/GSK-3β通路的激活和RPF2过表达诱导的EMT。体外和体内实验均证实RPF2表达水平与CRC细胞的转移潜能呈正相关。此外，CARM1抑制剂显著降低了rpf2过表达细胞的侵袭和迁移能力。这些发现表明，RPF2通过AKT/GSK-3β通路调节EMT驱动结直肠癌转移，而CARM1作为关键介质，为结直肠癌提供了潜在的治疗靶点。

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引用次数: 0

GPC-3 in hepatocellular carcinoma; A novel biomarker and molecular target GPC-3在肝细胞癌中的表达；一种新的生物标志物和分子靶点。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114391

Hamed Azhdari Tehrani , Masood Zangi , Mobina Fathi , Kimia Vakili , Moustapha Hassan , Elham Rismani , Nikoo Hossein-Khannazer , Massoud Vosough

Hepatocellular carcinoma (HCC) is a global health issue due to its late diagnosis and high recurrence rate. The early detection and diagnosis of HCC with specific and sensitive biomarkers and using novel treatment approaches to improve patient outcomes are essential. Glypican-3 (GPC-3) is a cell surface proteoglycan that is overexpressed in many tumors, including HCC. GPC-3 could be used as a specific biomarker for HCC early detection and could be a potential target for precise therapeutic strategies. Effective identification of GPC-3 could improve both diagnosis and targeted therapy of HCC. Moreover, targeted therapy using GPC-3 could result in a better treatment outcome. Recently, GPC3-targeted therapies have been used in different investigational therapeutic approaches like bi-specific/monoclonal antibodies, peptide vaccines, and CAR T cell therapies. This study aims to highlight the theranostic potential of GPC-3 as a novel biomarker for early detection and as a potential molecular target for HCC treatment as well.

肝细胞癌（HCC）因其诊断晚、复发率高而成为一个全球性的健康问题。HCC的早期检测和诊断具有特异性和敏感性的生物标志物，并使用新的治疗方法来改善患者的预后是至关重要的。Glypican-3 （GPC-3）是一种细胞表面蛋白聚糖，在包括HCC在内的许多肿瘤中过表达。GPC-3可以作为HCC早期检测的特异性生物标志物，并可能成为精确治疗策略的潜在靶点。GPC-3的有效鉴定有助于肝癌的诊断和靶向治疗。此外，使用GPC-3进行靶向治疗可能会产生更好的治疗效果。最近，gpc3靶向治疗已被用于不同的研究性治疗方法，如双特异性/单克隆抗体、肽疫苗和CAR - T细胞治疗。本研究旨在强调GPC-3作为早期检测的新型生物标志物和HCC治疗的潜在分子靶点的治疗潜力。

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引用次数: 0

Müller glia in short-term dark adaptation of the Austrolebias charrua retina: Cell proliferation and cytoarchitecture 视网膜短期暗适应中的突触神经胶质：细胞增殖和细胞结构。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114394

Laura Herrera-Astorga , Stephanie Silva , Inés Berrosteguieta , Juan Carlos Rosillo , Anabel Sonia Fernández

Fish with unique life cycles offer valuable insights into retinal plasticity, revealing mechanisms of environmental adaptation, cell proliferation, and thus, potentially regeneration. The variability of the environmental factors to which Austrolebias annual fishes are exposed has acted as a strong selective pressure shaping traits such as nervous system plasticity. This has contributed to adaptation to their extreme conditions including the decreased luminosity as ponds dry out. In particular, the retina of A. charrua has been shown to respond to 30 days of decreased luminosity by exacerbating cell proliferation Now, we aimed to determine the cellular component of the retina involved in shorter-term responses. To this end, we performed 5-bromo-2′-deoxyuridine (BrdU) experiments, exposing adult fish to a short period (11 days) of constant darkness. Strikingly, in control conditions, neurogenesis in the inner nuclear and ganglion cell layer in the differentiated retina was detected. In constant darkness, we observed an effect on inner nuclear layer cell proliferation and changes in retinal cytoarchitecture of the retina with cell clusters located in the inner plexiform layer. Additionally, increased BLBP (brain lipid-binding protein) presence was detected in darkness, which has been previously associated with immature and reactivated Müller glia. Thus, our results suggest that the A. charrua retina can respond to environmental changes via rapid activation of progenitor cells in the INL, namely the Müller glia This leads us to hypothesize, that cell proliferation and neurogenesis might contribute to the responses to the functional needs of organisms, potentially playing an adaptive role.

具有独特生命周期的鱼类为研究视网膜可塑性提供了有价值的见解，揭示了环境适应、细胞增殖以及潜在再生的机制。黄鳝所处环境因子的变异性是形成其神经系统可塑性等特征的一种强大的选择压力。这有助于适应它们的极端条件，包括池塘干涸时亮度下降。特别的是，研究表明，在30天的亮度下降后，黄花蒿的视网膜会通过加剧细胞增殖来做出反应。现在，我们的目标是确定视网膜中参与短期反应的细胞成分。为此，我们进行了5-溴-2'-脱氧尿嘧啶（BrdU）实验，将成年鱼暴露在短时间（11天）的持续黑暗中。引人注目的是，在对照条件下，在分化视网膜的细胞核和神经节细胞层中检测到神经发生。我们观察到持续黑暗对视网膜内核层细胞增殖的影响和视网膜细胞结构的变化，细胞团位于视网膜内丛状层。此外，在黑暗中检测到BLBP（脑脂结合蛋白）的增加，这与未成熟和重新激活的神经胶质细胞有关。因此，我们的研究结果表明，A. charrua视网膜可以通过快速激活INL中的祖细胞（即m ller胶质细胞）来响应环境变化。这使我们假设，细胞增殖和神经发生可能有助于对生物体功能需求的反应，潜在地发挥适应性作用。

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