Molecular immunology最新文献

{"title":"CRISPR-Cas9 engineering of human T regulatory cells – Design and optimization of a manufacturing process","authors":"Ortal Shimon ,&nbsp;Adam M. Dean ,&nbsp;Shoshana Cohen ,&nbsp;Aiden L. Moser ,&nbsp;Clifford C. Dacso ,&nbsp;Yosi Gilad ,&nbsp;David M. Lonard ,&nbsp;Bert W. O’Malley","doi":"10.1016/j.molimm.2025.05.019","DOIUrl":"10.1016/j.molimm.2025.05.019","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) are a subset of CD4 + T cells that comprise 5–10 % of the total CD4 + T cell population. Tregs, which are critically important for the maintenance of immune tolerance and immune homeostasis, are distinguished from other subtypes of CD4 + T cells by the expression of the transcription factor FOXP3. Because of the centrality to immunoregulation, Tregs have gained increasing attention as promising targets for clinical applications in autoimmune diseases, transplant rejection and graft-versus-host disease (GvHD). However, the essential role of Tregs in the complex network of the immune system implies their targeting as a promising therapeutic approach also in other medical indications, such as neurodegenerative diseases and cancer. Our group recently published a study showing that genetically modified Tregs are capable of clearing solid malignancies in various mice models, including an aggressive triple negative breast cancer (TNBC) and prostate cancer, which provides the impetus to develop an adoptive cell therapy using Steroid Receptor Coactivator 3 (SRC-3) knock out (KO) Tregs. It is well known that isolation, genetic editing and the expansion of Tregs as a homogenous and healthy population present specific technical challenges. In this context, here we outline the development of a process for the production of SRC-3 KO human Tregs (hTregs), which can subsequently be adapted for Current Good Manufacturing Practice (cGMP) settings to facilitate clinical-scale production.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 13-21"},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAA1 deletion ameliorates cardiac injury after myocardial infarction by promoting macrophage transformation to reparative subtype","authors":"Yingjie Xu ,&nbsp;Ke Zhang ,&nbsp;Changqun Sun,&nbsp;Qi Zhang,&nbsp;Bingxin Li,&nbsp;Yongjie Yuan,&nbsp;Jie Wang,&nbsp;Jintong Zhang,&nbsp;Yajie Chang,&nbsp;Shu Wang,&nbsp;Jia Li","doi":"10.1016/j.molimm.2025.05.022","DOIUrl":"10.1016/j.molimm.2025.05.022","url":null,"abstract":"<div><h3>Background</h3><div>The regulation of M1/M2 macrophage phenotypic conversion is an effective therapeutic strategy for post-myocardial infarction (MI). Serum Amyloid A1 (SAA1) is an acute-phase protein that plays an important role in regulating inflammatory responses. However, its function in modulating macrophage polarization post-MI remains unclear.</div></div><div><h3>Methods</h3><div>To achieve macrophage-specific manipulation of SAA1 expression in vivo, adeno-associated virus 9 (AAV9) vectors driven by a macrophage-specific promoter (F4/80) were used to either knockdown (AAV9-F4/80-sh-SAA1) or overexpress (AAV9-F4/80-SAA1) SAA1. Two weeks after the virus injection, mice underwent MI and ischemia-reperfusion (I/R) surgery. Each group included six mice. Immunofluorescence (IF), western blotting, and quantitative real-time polymerase chain reaction were performed to explore the mechanisms underlying SAA1-induced macrophage polarization and cardiac injury after MI and I/R. SAA1 was overexpressed and knocked down in lipopolysaccharide-stimulated bone marrow-derived macrophages in vitro using plasmids and siRNA. IF, western blotting, and quantitative real-time polymerase chain reaction were used to measure macrophage polarization and inflammatory responses.</div></div><div><h3>Results</h3><div>We detected a significant increase in SAA1 levels in human and mouse peripheral blood mononuclear cells after MI and I/R. Following SAA1 knockout, left ventricular ejection fraction (64.33 ± 2.35 % versus 40.97 ± 8.36 %) was significantly improved and infarcted size (93.95 ± 3.79 % versus 29.76 ± 17.05 %) was markedly reduced in MI+AAV-9-F4/80-Sh-SAA1 compared with MI+AAV-9-F4/80-Sh-NC. Similarly, the accumulation of M1 macrophages in the infarcted tissues was reduced by SAA1 deletion. Mechanistically, these effects were partially mediated by inhibition of via the p38 MAPK signaling pathway.</div></div><div><h3>Conclusion</h3><div>SAA1 activated the p38 MAPK pathway to contribute to macrophage polarization and the release of inflammatory factors and subsequently exacerbated cardiac injury and inflammatory response post-MI and I/R.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Andrographolide and its sulfated metabolite alleviated DSS-induced inflammatory bowel disease through regulating inflammation and immune via MAPK/NLRP3 pathways and the balance of Th17/Treg cells","authors":"Hui-Lin Zhang ,&nbsp;Jing Chang ,&nbsp;Cheng-Peng Sun ,&nbsp;Zhi-Peng Huo ,&nbsp;Yan-Li Feng ,&nbsp;Peng-Yan Li ,&nbsp;Ya-Xue Jia ,&nbsp;Si-Wen Hui ,&nbsp;Qi-Meng Zhu ,&nbsp;Jin-Yong Cai ,&nbsp;Yi He ,&nbsp;Feng Qiu ,&nbsp;Juan Zhang","doi":"10.1016/j.molimm.2025.05.015","DOIUrl":"10.1016/j.molimm.2025.05.015","url":null,"abstract":"<div><div>Inflammatory Bowel Disease (IBD), is a chronic illness characterized by severe abdominal pain, diarrhea, and weight loss, seriously diminishing patients’ quality of life. Andrographolide (AND), a natural diterpenoid from <em>Andrographis paniculata</em>, and its sulfated metabolite, andrographolide sodium bisulfite (ASB), have showed potential anti-inflammatory effects. However, their mechanism in IBD remains elusive. This study investigated the impact of AND and its sulfated derivative ASB, on inflammatory responses in IBD. Our findings revealed that AND and ASB significantly reduced disease activity index (DAI) scores and enhanced intestinal barrier function in dextran sodium sulfate (DSS)-induced mice, thereby ameliorating the course of IBD. Furthermore, AND and ASB inhibited both the mitogen-activated protein kinase (MAPK) and NLRP3 pathways to reduce the release of inflammatory cytokines IL-6 and TNF-α. This mechanism was accompanied by a restoration of immune balance through the modulation of T-helper 17 (Th17) and regulatory T (Treg) cells. The ability of AND and ASB to mitigate chronic inflammation and maintain immune equilibrium presented a promising therapeutic approach for IBD management. These findings suggested that AND and ASB might provide novel therapeutic approaches for IBD, thereby warranting further investigation into their clinical efficacy for disease treatment and maintenance of remission.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 313-320"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome-wide reverse vaccinology to identify potential vaccine candidates against Staphylococcus aureus","authors":"Aysan Salemi ,&nbsp;Mohammad M. Pourseif ,&nbsp;Yosef Masoudi-Sobhanzadeh ,&nbsp;Rais Ansari ,&nbsp;Yadollah Omidi","doi":"10.1016/j.molimm.2025.05.016","DOIUrl":"10.1016/j.molimm.2025.05.016","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> is a common cause of infections, both in the community and in healthcare settings, ranging from mild to severe cases that can often be life-threatening. Previous attempts to develop effective vaccines against <em>S. aureus</em> have been somewhat unsuccessful, emphasizing the need to explore its proteome and identify potential targets for vaccine development. This study aimed to comprehensively analyze the <em>S. aureus</em> proteome using network-based interactomics and high-throughput reverse screening techniques to identify promising vaccine candidates. We employed a computational proteome screening platform that integrated data from various sources, including experimental findings from a thorough literature review. By combining these datasets, we identified eighteen protein vaccine targets that demonstrated strong potential in eliciting an immune response against <em>S. aureus</em>. This approach is significant as it sheds light on the crucial pathways involved in the survival and pathogenesis of <em>S. aureus</em> while identifying key proteins within these pathways involved in its pathogenesis. This study serves as a proof-of-principle, demonstrating the potential of a customized platform designed specifically to discover vaccine candidates against <em>S. aureus</em> and tackle its canonical infections.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 296-312"},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using novel approaches to conjugate peptides of Macrotermes bellicosus and Curcuma longa for targeted intervention of irritable bowl diseases caused by tumor necrosis factor superfamily member 15 (TNFSF15)","authors":"Muhammad Naveed ,&nbsp;Muhammad Azan Ali Choudary ,&nbsp;Tariq Aziz ,&nbsp;Syeda Izma Makhdoom ,&nbsp;Sana Rehman Cheema ,&nbsp;Nureen Zahra ,&nbsp;Rania Ali El Hadi Mohamed ,&nbsp;Fahad Al-Asmari ,&nbsp;Fakhria A. Al-Joufi ,&nbsp;Maher S. Alwethaynani ,&nbsp;Deema Fallatah","doi":"10.1016/j.molimm.2025.05.018","DOIUrl":"10.1016/j.molimm.2025.05.018","url":null,"abstract":"<div><div>This study presents an in-silico approach to develop targeted therapies for Irritable Bowel Disease (IBD) by focusing on TNFSF15. Peptides derived from <em>Macrotermes bellicosus</em> and <em>Curcuma longa</em> were selected, conjugated with the 50S ribosomal protein L7/L12 adjuvant, and analyzed for immunogenic potential. Gene expression analysis showed differential TNFSF15 expression in gastrointestinal tissues. Functional enrichment revealed its role in immune regulation and cytokine signaling. Of the 20 peptides identified, 8 showed high antigenicity and 4 were allergenic. Structural modeling and docking predicted stable interactions with TNFSF15 (binding energy: –9.4 kJ/mol), supported by molecular dynamics. Immune simulations indicated robust IgM and IgG responses. These findings suggest that plant and insect derived peptides may offer promising therapeutic candidates for TNFSF15-associated IBD.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 286-295"},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in complement activation of serum-resistant and serum-sensitive Klebsiella pneumoniae isolates","authors":"Mikkel Eggert Thomsen ,&nbsp;Tue Bjerg Bennike ,&nbsp;Gunna Christiansen ,&nbsp;Jeppe Emmersen ,&nbsp;Nick Stub Laursen ,&nbsp;Alessandra Zarantonello ,&nbsp;Gregers Rom Andersen ,&nbsp;Lei Liu ,&nbsp;Morten Kam Dahl Dueholm ,&nbsp;Katharina V. Opstrup ,&nbsp;Allan Stensballe ,&nbsp;Svend Birkelund","doi":"10.1016/j.molimm.2025.05.014","DOIUrl":"10.1016/j.molimm.2025.05.014","url":null,"abstract":"<div><div>The gram-negative bacteria <em>Klebsiella pneumoniae</em> are genetically heterogeneous and a common cause of sepsis and bacteremia in humans. The complement system is the first line of defence against bacteria when they invade the body. We previously investigated <em>K. pneumoniae</em> isolates from sepsis patients. We found that complement factor (C) 3 is deposited on all isolates independent of serum sensitivity, but the membrane attack complex (MAC) was only formed on the serum-sensitive isolates. To investigate the mechanism for serum resistance, we incubated one serum-sensitive and one serum-resistant isolate in human serum and identified bound complement factors by mass spectrometry. The serum-sensitive isolate had all expected complement factors bound, including C4, while the serum-resistant isolate had only C3 bound. The serum resistance was caused by a fast cleavage of C3b to iC3b. Thereby, the C5 convertase, and thus MAC, cannot be formed. To confirm the role of C4 in serum sensitivity, C4 was inhibited by the nanobody hC4Nb8, resulting in the survival of the serum-sensitive isolate. This suggests that C4 is indispensable for MAC formation through the classical and lectin pathways. In contrast, when activated selectively, the alternative pathway primarily leads to the generation of iC3b, thereby enabling serum resistance by bypassing MAC assembly.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 274-285"},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indications of trained innate immunity by Escherichia coli vaccination or chitin feed supplementation assessed during Ascaridia galli infection in chickens","authors":"Mona Moosavi ,&nbsp;Rikke Brødsgaard Kjærup ,&nbsp;Konstantinos Papanikolaou ,&nbsp;Eva Wattrang ,&nbsp;Tina Sørensen Dalgaard","doi":"10.1016/j.molimm.2025.05.008","DOIUrl":"10.1016/j.molimm.2025.05.008","url":null,"abstract":"<div><div>Infections with the gastrointestinal roundworm <em>Ascaridia galli</em>, cause health problems and economic losses in laying hen husbandry, particularly in organic and free-range systems. This study aimed to evaluate induction of trained innate immunity through priming with a live attenuated <em>Escherichia coli</em> vaccine or chitin supplementation in the feed as a novel approach to mitigate <em>A. galli</em> infection. The study comprised four groups of chickens: chitin-fed (day 1–7 of age), <em>E. coli</em>-vaccinated (day 1 of age), an untreated control group, and a naïve uninfected group. On day 7 of age, the first three groups were infected with <em>A. galli</em>. Immune parameters were assessed after initial treatments and post the parasite infection. Also, faecal excretion of nematode eggs and total worm burden were monitored post-infection. The chitin and <em>E. coli</em> treatments induced changed proportions of leukocytes in bone marrow as well as changes in cell surface receptor expression. Moreover, treatments altered the immune response to the <em>A. galli</em> infection, e.g. observed for numbers of heterophils and TCRγδ+CD8- T-cells in the circulation but also expression levels of cell surface receptors CD41/61, Bu-1 and MHC-II on circulating leukocyte subsets. However, neither treatment affected worm burden, faecal egg excretion or the induction of <em>A. galli</em>-specific IgY. The results demonstrate potential <em>in vivo</em> training of the avian innate immune system but further research is needed to identify strategies to explore this in relation to control of nematode infections.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 246-258"},"PeriodicalIF":3.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative transcriptomic analyses of macrophages infected with Toxoplasma gondii strains of different virulence provide molecular insights into the response of macrophage in phagocytosis and polarization to infection","authors":"Shifan Zhu ,&nbsp;Jiantao Liu ,&nbsp;Kangzhi Xu ,&nbsp;Fan Xu ,&nbsp;Yuwei Jiang ,&nbsp;Linwei Dai ,&nbsp;Tianxu Pei ,&nbsp;Yuyang Zhu ,&nbsp;Dandan Liu ,&nbsp;Xinjun Zhang ,&nbsp;Jinjun Xu ,&nbsp;Jin Yang ,&nbsp;Zhiming Pan ,&nbsp;Jianping Tao ,&nbsp;Zhaofeng Hou","doi":"10.1016/j.molimm.2025.05.003","DOIUrl":"10.1016/j.molimm.2025.05.003","url":null,"abstract":"<div><div>Macrophages are essential for the proliferation and spread of <em>Toxoplasma gondii</em>. Modulating macrophage activation to improve the inflammatory environment is an effective approach for disease treatment. However, the molecular mechanism through which <em>T. gondii</em> alters macrophage function remain unknown. Based on transcriptomic data analysis of various macrophage types infected with <em>T. gondii</em>, current research revealed differences in the regulation of macrophage functions among strains with different virulence: RH was primarily involved in cell cycle regulation, ME49 was associated with cAMP signaling, and CEP mainly participated in ion channel activity. All three <em>T. gondii</em> strains were involved in regulating immune response activation, including leukocyte adhesion and the MAPK signaling pathway. Nineteen shared DEGs associated with macrophage phagocytosis or polarization were identified through the GeneCards database, and PPI analysis confirmed <em>Il6</em> as the hub gene in the regulatory network. In <em>vivo</em> and in <em>vitro</em> experiments showed that the YZ-1 strain significantly regulated the expressions of eight DEGs (<em>Il6</em>, <em>Rel</em>, <em>Cd83</em>, <em>Myc</em>, <em>Adora2b</em>, <em>Egr2</em>, <em>Gja1</em> and <em>Nr4a2</em>), and promoted macrophage phagocytic activity and induced M1 polarization, confirming a significant correlation with <em>Il6</em>. This study revealed the dissimilarities and commonalities in macrophage function regulated by <em>T. gondii</em> strains of different virulence, and identified key molecules involved in the regulation of macrophage phagocytosis and polarization during <em>T. gondii</em> infection. This is crucial for identifying potential drug targets against <em>T. gondii</em> and provides a new perspective on the etiopathogenesis and therapeutic approaches for toxoplasmosis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 259-273"},"PeriodicalIF":3.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helicobacter pylori delays neutrophil apoptosis but also drives the formation of cells with a leaky plasma membrane: Implications for inflammation","authors":"Tran Duong Thai ,&nbsp;Chatcharin Kamsom ,&nbsp;Wisitsak Phoksawat ,&nbsp;Arnone Nithichanon ,&nbsp;Kiatichai Faksri ,&nbsp;Banchob Sripa ,&nbsp;Steven W. Edwards ,&nbsp;Kanin Salao","doi":"10.1016/j.molimm.2025.05.006","DOIUrl":"10.1016/j.molimm.2025.05.006","url":null,"abstract":"<div><div><em>Opisthorchis viverrini</em> (OV)-induced cholangiocarcinoma (CCA) is a significant public health concern in countries in the Lower Mekong Basin. OV is a reservoir for <em>Helicobacter pylori</em> (<em>H. pylori</em>), and so many individuals are co-infected with these two biological carcinogens. Our study aimed to investigate interactions between <em>H. pylori</em> isogenic strains possessing or lacking the pathogenicity factor CagA (<em>cag</em>A+ and <em>cag</em>A-) with neutrophils. Both <em>H. pylori</em> strains were co-cultured with neutrophils <em>in vitro</em>, and neutrophil activation, phagocytosis, reactive oxygen species (ROS) production, and cell survival/apoptosis were measured. Both isogenic strains of <em>H. pylori</em> stimulated phagocytosis and while the <em>cag</em>A- strain induced slightly higher ROS production, both strains served as potent activators of neutrophils. Notably, <em>H. pylori</em> induced rapid cell death in a sub-population of neutrophils after 30 min of co-incubation while extending the lifespan of the neutrophils that survived this initial cell death. This initial incubation resulted in the appearance of propidium iodide (PI)+ neutrophils, i.e. cells with a compromised plasma membrane that could result in the release of inflammation-promoting neutrophil contents. While significantly more viable neutrophils were detected after 24 h (and 48 h) incubation with <em>H. pylori</em>, those cells that did not survive also showed characteristics of a compromised plasma membrane (i.e. PI+). We propose that the combinations of PI+ neutrophils with leaky plasma membranes and non-apoptotic neutrophils with enhanced survival after incubation with <em>H. pylori</em> may drive persistent inflammation. These findings offer new insights into the immunopathogenesis of OV and <em>H. pylori</em> co-infections, which may help improve OV treatment strategies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 236-245"},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA SNHG12 promotes EMT and metastasis of colorectal cancer via regulating TGF-β/Smad2/3 signaling pathway","authors":"Lei Zhao ,&nbsp;Yuan Chang ,&nbsp;Xiaoli Sun ,&nbsp;Hongliang Chen ,&nbsp;Ning Li ,&nbsp;Tianyi Ma ,&nbsp;Shizhu Jin","doi":"10.1016/j.molimm.2025.05.017","DOIUrl":"10.1016/j.molimm.2025.05.017","url":null,"abstract":"<div><h3>Objective</h3><div>In this study, we aimed to explore the molecular mechanism of SNHG12 promoting colorectal cancer (CRC) progression.</div></div><div><h3>Methods</h3><div>Bioinformatics technology was utilized to identify SNHG12-targeted mRNA and the correlation with the prognosis of CRC patients. Transfected sequence of knockdown SNHG12 in HCT-116 cell line was established. CCK8 assay, colone formation assay, flow cytometry, cell migration and transwell assay were applied to detect the impact of SNHG12 on HCT-116 cells. Besides, qRT-PCR and western blot were employed to evaluate the apoptotic and EMT markers as well as the expression of TGF-β and p-Smad2/3. Additionally, the rescue test of overexpressing TGF-β and a nude mouse subcutaneous tumor model were established to validate the pivotal role of SNHG12 in driving the progression of CRC.</div></div><div><h3>Results</h3><div>SNHG12 could predict the prognosis of CRC patients, and a target mRNA GOLT1B was obtained from bioinformatics. In vitro results indicated that SNHG12 facilitated the proliferation, migration, and invasion of HCT-116 cells. qRT-PCR and western blot showed SNHG12 was related to the expression of Caspase 3, EMT markers as well as TGF-β and p-Smad2/3. Meanwhile, the rescue experiment proved that overexpressed TGF-β had the ability to reverse the impact of SNHG12 knockout on cell function and phenotype. In vivo, SNHG12 knockdown significantly reduced tumor growth.</div></div><div><h3>Conclusion</h3><div>SNHG12 promotes EMT and metastasis of CRC by modulating the TGF-β/Smad2/3 signaling pathway and EMT process, which could function as a prognostic biomarker and a treatment target for CRC.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 225-235"},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}