Experimental cell research最新文献

{"title":"The intervention of B. longum metabolites in Fnevs' carcinogenic capacity: A potential double-edged sword","authors":"Jingyu Xu ,&nbsp;Xinyu Wu ,&nbsp;Luyi Yang ,&nbsp;Xiaoxi Xu","doi":"10.1016/j.yexcr.2025.114407","DOIUrl":"10.1016/j.yexcr.2025.114407","url":null,"abstract":"<div><div>Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. <em>Fusobacterium nucleatum</em> and its metabolites are effective biological targets for colon cancer promotion. Probiotics such as <em>Bifidobacterium</em> can block the occurrence and development of CRC by regulating the host intestinal mucosal immunity, eliminating carcinogens, and interfering with tumor cell proliferation and apoptosis. We selected six <em>Bifidobacterium</em> species to explore the inhibitory effect of their cell-free supernatant (CFS) on <em>Fusobacterium nucleatum</em>, and screened the best functional strain <em>Bifidobacterium longum</em> (<em>B. longum</em>) to explore its intervention effect on Fnevs infection of CRC cells. In the genus <em>Bifidobacterium</em>, <em>B. longum</em>-CFS can effectively inhibit the growth and membrane formation of <em>Fusobacterium nucleatum</em>. The metabolites of <em>B. longum</em> can inhibit the proliferation, migration and invasion of Fnevs-infected CRC cells. However, the transcriptomic analysis of Fnevs-infected CRC cells treated with Bl-CFS revealed that Bl-CFS exerted inhibitory effects on the expression of specific oncogenes (e.g., Myc, IL16, KCNN2, ACSBG1, Pum1, MET, NR5A2), while simultaneously promoting the expression of other oncogenes. This modulation potentially enhances the proliferation, epithelial-mesenchymal transition (EMT), stemness properties and other characteristics associated with CRC cells. Metabolomics also showed that Bl-CFS altered organic acid and lipid metabolism in Fnevs-infected CRC cells, and switched energy supply from aerobic glucose metabolism (TCA cycle) to anaerobic glycolysis, which increased the malignancy potential of CRC cells. The observed outcome may be attributed to the presence of both probiotics and toxic substances in the metabolites derived from <em>Bifidobacterium longum</em>. Therefore, this study concludes that the anti-colorectal cancer (CRC) effect of natural metabolites derived from <em>Bifidobacterium longum</em> is limited. Future investigations should focus on refining these natural substances and optimizing their composition ratios to extract their essence while eliminating impurities, thereby obtaining anticancer biologics with exceptional and consistent efficacy.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"445 1","pages":"Article 114407"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964314","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}

{"title":"Ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate inhibits the malignant biological behaviors of colorectal cancer by restricting the phosphorylation and nuclear translocation of STAT3","authors":"Jie Lin ,&nbsp;Weijing Liu ,&nbsp;Xiaodan Li ,&nbsp;Jiansuo Lin ,&nbsp;Xuehong Fang ,&nbsp;Yanwen Liang ,&nbsp;Wen Zhang ,&nbsp;Jianwei Ren ,&nbsp;Feng Wang ,&nbsp;Liyi Zou ,&nbsp;Yi Liu","doi":"10.1016/j.yexcr.2025.114421","DOIUrl":"10.1016/j.yexcr.2025.114421","url":null,"abstract":"<div><div>To investigate the effect of a novel coumarin derivative, ethyl 2,2-difluoro-2 - (2-oxo-2H-chromen-3-yl) acetate (C2F), on the malignant biological behaviors of colorectal cancer (CRC) and elucidate its mechanism. <em>In vitro</em>, the effects of C2F on the proliferation, apoptosis, migration, invasion, and cell cycle of CRC cells were analyzed by MTT assay, EdU staining, colony formation assay, flow cytometry, wound healing and transwell assay. The anti-CRC activity of C2F was evaluated in a nude mice xenograft model <em>in vivo</em>. Western blot was conducted to detect the expression of protein in cells and mice tissue. Then, the potential targets of C2F in CRC were predicted by network pharmacology analysis and molecular docking. The localization of STAT3 was observed through immunofluorescence experiment. C2F inhibits CRC cell proliferation, promotes CRC cell apoptosis, hinders CRC cell migration and invasion, and prevents the cell cycle from entering the G2/M phase. <em>In vivo</em>, C2F inhibited tumor growth in xenograft model. C2F inhibited signal transduction and activator of transcription 3 (STAT3) phosphorylation and blocked interleukin-6 (IL-6)-induced STAT3 nuclear translocation. C2F inhibits the malignant biological behavior of CRC by limiting STAT3 phosphorylation and entry into the nucleus.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"445 2","pages":"Article 114421"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045997","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}

{"title":"FOXA2 regulates endoplasmic reticulum stress, oxidative stress, and apoptosis in spermatogonial cells by the Nrf2 pathway under hypoxic conditions","authors":"Weiwei Li ,&nbsp;Xiurong Yin ,&nbsp;Lei Zhang","doi":"10.1016/j.yexcr.2024.114388","DOIUrl":"10.1016/j.yexcr.2024.114388","url":null,"abstract":"<div><div>Hypoxia-caused spermatogenesis impairment may contribute to male infertility. FOXA2 has been found to be abundant in spermatogonial stem cells and critical for spermatogenesis. Here we aimed to explore the roles of FOXA2 in regulating spermatogonial cells against hypoxia stimulation. Our results showed that FOXA2 expression was downregulated in hypoxia-stimulated spermatogonial cells. Overexpression of FOXA2 prevented hypoxia-induced endoplasmic reticulum (ER) stress with decreased expression levels of associated markers including GRP78, CHOP, and ATF-4. FOXA2 overexpression caused a decrease in MDA content and an increase in activities of SOD, CAT, and GSH-Px in spermatogonial cells under hypoxic conditions, implying its inhibitory effect on oxidative stress. Besides, cell apoptosis under hypoxic conditions was also prevented by FOXA2 overexpression, as shown by reduced apoptotic rate and caspase-3 activity. Moreover, we found that hypoxia stimulation inactivated the Nrf2 pathway, which could be prevented by FOXA2 overexpression. Nrf2 knockdown attenuated the effects of FOXA2 overexpression on hypoxia-induced ER stress, oxidative stress, and apoptosis in spermatogonial cells. In conclusion, FOXA2 exerted protective effects on spermatogonial cells against hypoxia-induced ER stress, oxidative stress, and apoptosis via regulating Nrf2/HO-1 signaling. These findings suggested that FOXA2 might be a therapeutic target for treating hypoxia-induced spermatogenesis impairment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114388"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863896","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}

{"title":"Knockdown of PELI1 promotes Th2 and Treg cell differentiation in juvenile idiopathic arthritis","authors":"Dan Li ,&nbsp;Xiaoqing Li ,&nbsp;Mingyue Duan ,&nbsp;Xiuhong Xue ,&nbsp;Xianyan Tang ,&nbsp;Nan Nan ,&nbsp;Rui Zhao ,&nbsp;Wenhua Zhang ,&nbsp;Wanggang Zhang","doi":"10.1016/j.yexcr.2024.114360","DOIUrl":"10.1016/j.yexcr.2024.114360","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114360"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767477","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}

{"title":"ALDH2 plays a role in spermatogenesis and male fertility by regulating oxidative stress in mice","authors":"Ying Lv ,&nbsp;Xing Yang ,&nbsp;Xiaoli Sun ,&nbsp;Linxiao Lv ,&nbsp;Zexin Zhang ,&nbsp;Chenyang Li ,&nbsp;Jiangang Gao ,&nbsp;Huatao Li ,&nbsp;Zongzhuang Wen ,&nbsp;Haixia Zhu","doi":"10.1016/j.yexcr.2024.114397","DOIUrl":"10.1016/j.yexcr.2024.114397","url":null,"abstract":"<div><div>Spermatogenesis and sperm maturation are complex biological processes that involve intricate cellular and molecular interactions. The <em>Aldh2</em> gene is involved in the metabolism of specific aldehydes generated by oxidative stress. <em>Aldh2</em> is abundantly expressed in the testis and epididymis; however, the specific role of <em>Aldh2</em> in regulating spermatogenesis and sperm maturation remains unclear. In the present study, we generated <em>Aldh2</em> knockout (<em>Aldh2</em>^{<em>−/−</em>}) mice by using CRISPR/Cas9 technology. <em>Aldh2</em> gene knockout decreased the fertility of male mice. Compared to the control group mice, <em>Aldh2</em>^{<em>−/−</em>} 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 <em>Aldh2</em>^{<em>−/−</em>} mice, leading to oligoasthenoteratozoospermia in male mice. However, the caput epididymis and cauda epididymis in <em>Aldh2</em>^{<em>−/−</em>} 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 <em>Aldh2</em>^{<em>−/−</em>} mice, thus indicating increased oxidative stress in the reproductive system. Collectively, our findings demonstrate that <em>Aldh2</em> plays a critical role in spermatogenesis by regulating oxidative stress in mice.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114397"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893396","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}

{"title":"Ku70 targets BRD3-MYC/Cyclin D1 axis to drive hepatocellular carcinoma progression","authors":"Wenshuang Sun ,&nbsp;Ji Cheng ,&nbsp;Ruijun Zhao ,&nbsp;Yujie Xiang ,&nbsp;Yuting Li ,&nbsp;Cuifu Yu ,&nbsp;Yuanfei Deng ,&nbsp;Gengxi Cai ,&nbsp;Hongbiao Huang ,&nbsp;Qiucheng Lei ,&nbsp;Yuning Liao ,&nbsp;Qing Liu","doi":"10.1016/j.yexcr.2024.114404","DOIUrl":"10.1016/j.yexcr.2024.114404","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114404"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914068","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}

{"title":"The Ku protein family regulates hyperglycemia-induced vascular endothelial cell inflammation by modulating P300 levels","authors":"Qinqin Cai ,&nbsp;Qiao Zhao ,&nbsp;Qingxia Yang ,&nbsp;Min Zhu ,&nbsp;Fufen Meng ,&nbsp;Jihong Jiang","doi":"10.1016/j.yexcr.2024.114399","DOIUrl":"10.1016/j.yexcr.2024.114399","url":null,"abstract":"<div><div>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 <em>P300</em> and <em>Ese-1</em> play pivotal roles in hyperglycemia-induced endothelial inflammation. This study suggests that <em>P300</em> modulates <em>Ese-1</em> 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 (<em>Tnf-α</em>), <em>p65</em> phosphorylation, and monocyte chemotactic proteins <em>Mip-1β</em> and <em>Mip-2</em> 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, <em>P300</em> was found to be upregulated both in vitro and in vivo. Moreover, silencing <em>P300</em> reduced hyperglycemia-induced inflammatory effects, which could be reversed by overexpressing <em>Ese-1</em> in HRGECs. Further, <em>P300</em> was observed to interact with the <em>Ku</em> protein family (<em>Ku70/Ku86</em>), which were downregulated in the kidney tissues of diabetic mice and hyperglycemic HRGECs. si<em>Ku70</em> and si<em>Ku86</em> intensified hyperglycemia-induced endothelial inflammation, an effect counteracted by <em>P300</em> silencing. In essence, the <em>Ku</em> protein family interacts with <em>P300</em> to modulate <em>Ese-1</em> expression in HRGECs, thereby participating in hyperglycemia-induced endothelial inflammation.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114399"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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 ,&nbsp;Yuesong Yin ,&nbsp;Hecheng Zhou ,&nbsp;Binbin Jiang ,&nbsp;Ting Cai ,&nbsp;Song Wu ,&nbsp;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}

{"title":"LINC02987 suppression hepatocellular carcinoma progression by modulating autophagy via the miR-338-3p/ATG12 axis","authors":"Haiyan Fu ,&nbsp;Qiuhong Wang ,&nbsp;Haiwen Li ,&nbsp;Hongjuan Li ,&nbsp;Jie Li ,&nbsp;Yu Liu ,&nbsp;Futao Dang ,&nbsp;Lifeng Wang ,&nbsp;Xuan Zhang ,&nbsp;Yongrui Yang ,&nbsp;Yingrong Du","doi":"10.1016/j.yexcr.2024.114398","DOIUrl":"10.1016/j.yexcr.2024.114398","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114398"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RPF2 and CARM1 cooperate to enhance colorectal cancer metastasis via the AKT/GSK-3β signaling pathway","authors":"Cong Cheng ,&nbsp;KeMing Zhang ,&nbsp;MaCheng Lu ,&nbsp;Yuan Zhang ,&nbsp;Tong Wang ,&nbsp;Ye Zhang","doi":"10.1016/j.yexcr.2024.114374","DOIUrl":"10.1016/j.yexcr.2024.114374","url":null,"abstract":"<div><div>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 <em>in vitro</em> and <em>in vivo</em> 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.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114374"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}