Molecular BiotechnologyPub Date : 2024-10-01Epub Date: 2023-10-01DOI: 10.1007/s12033-023-00898-6
Zhijuan Hu, Chi Chen, Xinyao Zheng, Jingjie Yuan, Run Zou, Chengjian Xie
{"title":"Establishing Gene Expression and Knockout Methods in Esteya vermicola CBS115803.","authors":"Zhijuan Hu, Chi Chen, Xinyao Zheng, Jingjie Yuan, Run Zou, Chengjian Xie","doi":"10.1007/s12033-023-00898-6","DOIUrl":"10.1007/s12033-023-00898-6","url":null,"abstract":"<p><p>Pine wilt disease, which is caused by the nematode Bursaphelenchus xylophilus, is one of the most destructive forest diseases worldwide. Esteya vermicola, a nematophagous fungus, has emerged as a promising biological control agent. However, the limited availability of gene function analysis techniques hinders further genetic modification of this fungus. In this study, we employed a combination of enzymes (driselase, snailase, and cellulase) to enzymatically degrade the cell wall of the fungus, resulting in a high yield of protoplasts. Furthermore, by utilizing 0.6 M sucrose as an osmotic pressure stabilizer, we achieved a significant protoplast regeneration rate of approximately 31%. Subsequently, we employed the polyethylene glycol-mediated protoplast transformation method to successfully establish a genetic transformation technique for E. vermicola CBS115803. Additionally, through our investigation, we identified the Olic promoter from Aspergillus nidulans, which effectively enhanced the expression of the DsRed gene encoding a red fluorescent protein in E. vermicola CBS115803. Moreover, we successfully implemented a split-marker strategy to delete the EvIPMD gene in E. vermicola CBS115803. In summary, our findings present valuable experimental methodologies for gene function analysis in E. vermicola CBS115803.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2872-2881"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2024-10-01Epub Date: 2023-09-27DOI: 10.1007/s12033-023-00895-9
MinBo Jiang, Yang Li, WenWen Fan, XiaoYan Shen, Kai Jiang, DeGuo Wang
{"title":"Circ-KATNAL1 Knockdown Reduces Neuronal Apoptosis and Alleviates Spinal Cord Injury Through the miR-98-5p/PRDM5 Regulatory Axis.","authors":"MinBo Jiang, Yang Li, WenWen Fan, XiaoYan Shen, Kai Jiang, DeGuo Wang","doi":"10.1007/s12033-023-00895-9","DOIUrl":"10.1007/s12033-023-00895-9","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a common disease of the central nervous system. circRNAs play a crucial role in neurological disease. The purpose of this study was to investigate the role of circ-KATNAL1 in SCI and its regulatory mechanism. T9-L10 spinal segment of Sprague Dawley rats was compressed or contused after T10 laminectomy to establish the SCI rat model. Then, rats were divided into SCI group, si-NC group, si-circ-KATNAL1 group, si-circ-KATNAL1 + antagomir NC group, si-circ-KATNAL1 + miR-98-5p antagomir group, si-circ-KATNAL1 + oe-NC group, and si-circ-KATNAL1 + oe-PRDM5 group, with 6 rats in each group. There was another sham operation group that received no treatment. Basso, Beattie, and Bresnahan (BBB) scores were used to evaluate the neural function of rats. In addition to that, the pathological changes of spinal cord tissue, neuronal apoptosis, and inflammatory responses were correspondingly observed and analyzed. Quantitative measurements of circ-KATNAL1, miR-98-5p, and PRDM5 levels were conducted, as well as analyses of their interrelationship. Circ-KATNAL1 was up-regulated in the spinal cord tissue of SCI rats, and circ-KATNAL1 knockdown could improve neural function, alleviate pathological changes of spinal cord tissue, and inhibit neuronal apoptosis and inflammatory responses in SCI rats. For miR-98-5p, circ-KATNAL1 was an upstream factor, while PRDM5 was a downstream actor. miR-98-5p deficiency or PRDM5 restoration impaired the remission effect of circ-KATNAL1 knockdown on SCI. Circ-KATNAL1 knockdown reduces neuronal apoptosis and alleviates SCI through miR-98-5p/PRDM5 regulatory axis.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2841-2849"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41166817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2024-10-01Epub Date: 2023-10-25DOI: 10.1007/s12033-023-00911-y
Guanghui Jin, Zhuo Wang, Wei Zhou, Guyue Li
{"title":"The Role of Nrf2-ARE Signaling Pathway and Tatarinow Sweetflag Extract to Regulate the Acute Phase of Pilocarpine-Induced Epilepsy in Juvenile Rats.","authors":"Guanghui Jin, Zhuo Wang, Wei Zhou, Guyue Li","doi":"10.1007/s12033-023-00911-y","DOIUrl":"10.1007/s12033-023-00911-y","url":null,"abstract":"<p><p>To analyze the role of Nrf2-ARE signaling pathway in the regulation of the acute phase of pilocarpine-induced epilepsy in juvenile rats by Tatarinow Sweetflag Extract (TSE). One hundred and twenty SPF-grade Wistar male rats were were divided into five groups by random number table method, namely, normal group, model group, low-dose TSE group, high-dose TSE group, low-dose TSE + Nrf2 inhibitor Brusatol group (low-dose TSE + BRU group), and high-dose TSE + Nrf2 inhibitor Brusatol group (high-dose TSE + BRU group), with 20 rats in each group. The success rate of modelling in the model group, low-dose TSE group, high-dose TSE group, low-dose TSE + BRU group, high-dose TSE + BRU group were 60.00% (12/20), 65.00% (13/20), 65.00% (13/20), 70.00% (14/20), and 70.00% (14/20), respectively, showing no significant difference (P > 0.05). The latency and incidence of class IV and V, discharge amplitude as well as frequency of rats in the low- and high-dose TSE groups were lower than those in the model group (P < 0.05); the lipid peroxide and malondialdehyde concentrations in hippocampal tissues in the low- and high-dose TSE groups were lower than those in the model group (P < 0.05); The Nrf2, NQO-1 and HO- 1 protein and mRNA expression levels were increased in the low- and high-dose TSE groups compared with the model group (P < 0.05). The therapeutic effect of TSE in rats with acute epilepsy was satisfactory, and its mechanism of action may be related to activation of Nrf2-ARE signaling pathway to reduce the degree of oxidative stress.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2946-2955"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50158372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2024-10-01Epub Date: 2023-09-28DOI: 10.1007/s12033-023-00879-9
Arnab Mukherjee, Preeti Harigovind Yadav, K S Mukunthan
{"title":"Unveiling Potential Targeted Therapeutic Opportunities for Co-Overexpressed Targeting Protein for Xklp2 and Aurora-A Kinase in Lung Adenocarcinoma.","authors":"Arnab Mukherjee, Preeti Harigovind Yadav, K S Mukunthan","doi":"10.1007/s12033-023-00879-9","DOIUrl":"10.1007/s12033-023-00879-9","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is one of the most prevalent and leading causes of cancer deaths globally, with limited diagnostic and clinically significant therapeutic targets. Identifying the genes and processes involved in developing and progressing LUAD is crucial for developing effective targeted therapeutics and improving patient outcomes. Therefore, the study aimed to explore the RNA sequencing data of LUAD from The Cancer Genome Atlas (TCGA) and gene expression profile datasets involving GSE10072, GSE31210, and GSE32863 from the Gene Expression Omnibus (GEO) databases. The differential gene expression and the downstream analysis determined clinically significant biomarkers using a network-based approach. These therapeutic targets predominantly enriched the dysregulation of mitotic cell cycle regulation and revealed the co-overexpression of Aurora-A Kinase (AURKA) and Targeting Protein for Xklp2 (TPX2) with high survival risk in LUAD patients. The hydrophobic residues of the AURKA-TPX2 interaction were considered as the target site to block the autophosphorylation of AURKA during the mitotic cell cycle. The tyrosine kinase inhibitor (TKI) dacomitinib demonstrated the strong binding potential to hinder TPX2, shielding the AURKA destabilization. This in silico study lays the foundation for repurposing targeted therapeutic options to impede the Protein-Protein Interactions (PPIs) in LUAD progression and aid in future translational investigations.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2792-2803"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2024-10-01Epub Date: 2023-10-02DOI: 10.1007/s12033-023-00890-0
Swathy S Samban, Aparna Hari, Bhagyalakshmi Nair, Ayana R Kumar, Benjamin S Meyer, Arun Valsan, Vinod Vijayakurup, Lekshmi R Nath
{"title":"An Insight Into the Role of Alpha-Fetoprotein (AFP) in the Development and Progression of Hepatocellular Carcinoma.","authors":"Swathy S Samban, Aparna Hari, Bhagyalakshmi Nair, Ayana R Kumar, Benjamin S Meyer, Arun Valsan, Vinod Vijayakurup, Lekshmi R Nath","doi":"10.1007/s12033-023-00890-0","DOIUrl":"10.1007/s12033-023-00890-0","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the primary malignancy of hepatocytes and the second most common cause of cancer-related mortality across the globe. Despite significant advancements in screening, diagnosis, and treatment modalities for HCC, the mortality-to-incidence ratio remain unacceptably high. A recent study indicates that a minor population of HCCs are AFP negative or express the normal range of AFP levels. Although it is a gold standard and a more reliable biomarker in the advanced stage of HCC and poorly differentiated tumors, it does not serve as a suitable means for screening HCC. AFP plays a significant role in the development and progression of HCC and understanding its role is crucial. By examining the molecular mechanisms involved in AFP-mediated tumorigenesis, we can better understand HCC pathogenesis and identify potential therapeutic targets. This article details the role of alpha-fetoprotein (AFP) in the carcinogenic transformation of hepatocytes. The article also focuses on information about the structure, biosynthesis, and regulation of AFP at the gene level. Additionally, it discusses the immune evasion, metastasis, and control of gene expression that AFP mediates during HCC.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2697-2709"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41166816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2024-10-01Epub Date: 2023-10-11DOI: 10.1007/s12033-023-00878-w
CuiYu You, JianFeng Xing, JinYao Sun, Di Zhang, Yan Yan, YaLin Dong
{"title":"Anti-Inflammatory and Anti-Oxidant Impacts of Lentinan Combined with Probiotics in Ulcerative Colitis.","authors":"CuiYu You, JianFeng Xing, JinYao Sun, Di Zhang, Yan Yan, YaLin Dong","doi":"10.1007/s12033-023-00878-w","DOIUrl":"10.1007/s12033-023-00878-w","url":null,"abstract":"<p><p>Multi-methods have been developed to control ulcerative colitis. This research targeted to probe that lentinan combined with probiotics suppresses inflammation and oxidative stress responses in a dextran sulfate sodium (DSS)-induced colitis model. A mouse model of colitis was induced through oral administration with 2.5% DSS and treated with lentinan and probiotics independently or in combination. Then, bodyweight and Disease Activity Index (DAI) of mice were determined. Histopathology of colon tissue was analyzed, and apoptosis, inflammation and oxidative stress in the colon tissue of mice were observed. An HT-29 cell model of colitis was established by DSS stimulation and cultured with lentinan and/or probiotics to examine cell proliferation and apoptosis. The data discovered that after DSS induction of colitis, mice developed weight loss, increased DAI score, and shortened the length of colon. Also, severe histopathology of the colon, and increased apoptosis, inflammation and oxidative stress were recognizable. Lentinan could alleviate DSS-induced colitis, and the highest dose was the most significant. Probiotics could also relieve UC in mice, and mixed probiotics had a better therapeutic effect than single probiotics. Lentinan combined with probiotics could further alleviate DSS-induced colitis damage. In addition, lentinan combined with probiotics impaired apoptosis and enhanced proliferation of DSS-treated HT-29 cells. In a word, lentinan combined with probiotics reduces the inflammatory response and oxidative stress of UC.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2778-2791"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41205520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2024-10-01Epub Date: 2023-10-10DOI: 10.1007/s12033-023-00896-8
Bingxi Tang, Lei Bi, Yanbin Xu, Lili Cao, Xinli Li
{"title":"N<sup>6</sup>-Methyladenosine (m<sup>6</sup>A) Reader IGF2BP1 Accelerates Gastric Cancer Development and Immune Escape by Targeting PD-L1.","authors":"Bingxi Tang, Lei Bi, Yanbin Xu, Lili Cao, Xinli Li","doi":"10.1007/s12033-023-00896-8","DOIUrl":"10.1007/s12033-023-00896-8","url":null,"abstract":"<p><p>N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) functions as an important regulator in various human cancers, including gastric cancer. The immunotherapy targeting PD-1/PD-L1 has brought hope for advanced gastric cancer therapeutic. Here, present research aims to investigate the roles of m<sup>6</sup>A reader IGF2BP1 on gastric cancer tumor development and immune escape. Results indicated that IGF2BP1 up-regulated in the gastric cancer tissue and correlated with poor prognosis of gastric cancer patients. IGF2BP1 overexpression augmented the proliferation of co-cultured gastric cancer cells, and mitigated the CD8+ T cells mediated anti-tumor response, including IFN-γ secretion, surface PD-L1 level, and cytotoxicity of CD8+ T cells. Meanwhile, IGF2BP1 silencing exerted the opposite effects. In silico analysis revealed that there was a remarkable m<sup>6</sup>A modified site on PD-L1 mRNA. Moreover, the IGF2BP1 overexpression enhanced the stability of PD-L1 mRNA, thereby deteriorating the immune escape of gastric cancer cells. Collectively, these results describe a novel regulatory mechanism of IGF2BP1 by regulating PD-L1 through m<sup>6</sup>A epigenetic modification, which might provide insights for gastric cancer immunotherapies.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2850-2859"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41205522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Potential of Circulating miR-193b, miR-146b-3p and miR-483-3p as Noninvasive Biomarkers in Cutaneous Melanoma Patients.","authors":"Atefeh Mohammadloo, Yazdan Asgari, Aghil Esmaeili-Bandboni, Mohammad Ali Mazloomi, Seyedeh Fatemeh Ghasemi, Sima Ameri, Seyed Rouhollah Miri, Shahin Hamzelou, Hamid Reza Mahmoudi, Ziba Veisi-Malekshahi","doi":"10.1007/s12033-023-00893-x","DOIUrl":"10.1007/s12033-023-00893-x","url":null,"abstract":"<p><p>Melanoma is a destructive skin disease with few therapeutic options in the developed stage and therefore there is a critical need for reliable biomarkers for early diagnosis. In this context, microRNAs could play an important role as diagnostic biomarkers. Three datasets with accession numbers GSE31568, GSE61741 and GSE20994 were downloaded from the Gene Expression Omnibus (GEO) database. MATLAB software was used to analyze differentially expressed miRNAs between cutaneous melanoma plasma samples and normal plasma samples (control). Plasma levels of miR-193b, miR-146b-3p and miR-483-3p were evaluated by the RT-PCR method. Furthermore, linear regression followed by receiver operating characteristic analyses was performed to estimate whether selected plasma miRNAs were able to distinguish between cases and controls. Finally, the data were analyzed by unpaired Mann-Whitney U test using Graph pad prism 8 computer software. Specifically, miR-193b and miR-146b-3p were downregulated in the plasma of melanoma patients compared with control groups which were decreased 5 × <math> <msup><mrow><mn>10</mn></mrow> <mn>6</mn></msup> </math> -fold in miR-193b and 58-fold in miR-146b-3p, while miR-483-3p was upregulated 3.5-fold. After receiver operating characteristic (ROC) curve analysis, miR-193b with the most area under the curve (AUC: 1.00, 95% confidence interval 1.00-1.00, p < 0.0001) had the best discriminatory power, and miR-146b-3p had the large area under the curve (AUC: 0.96, 95% confidence interval 0.96-1.00, p < 0.0001) and consequently the high discriminatory power. Between these three miRNAs, miR-193b and miR-146b-3p had a high capacity to distinguish between melanoma patients and control groups that are appropriate to be applied in melanoma diagnosis as an early and noninvasive method.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2830-2840"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2024-10-01Epub Date: 2023-10-16DOI: 10.1007/s12033-023-00869-x
Qinhua Gan, Xinyu Cui, Lin Zhang, Wenxu Zhou, Yandu Lu
{"title":"Control Phytophagous Nematodes By Engineering Phytosterol Dealkylation Caenorhabditis elegans as a Model.","authors":"Qinhua Gan, Xinyu Cui, Lin Zhang, Wenxu Zhou, Yandu Lu","doi":"10.1007/s12033-023-00869-x","DOIUrl":"10.1007/s12033-023-00869-x","url":null,"abstract":"<p><p>Plant-parasitic nematodes ingest and convert host phytosterols via dealkylation to cholesterol for both structural and hormonal requirements. The insect 24-dehydrocholesterol reductase (DHCR24) was shown in vitro as a committed enzyme in the dealkylation via chemical blocking. However, an increased brood size and ovulation rate, instead compromised development, were observed in the engineered nematode Caenorhabditis elegans where the DHCR24 gene was knocked down, indicating the relationship between DHCR24 and dealkylation and their function in nematodes remains illusive. In this study, a defect in C. elegans DHCR24 causes impaired growth of the nematode with sitosterol (a major component of phytosterols) as a sole sterol source. Plant sterols with rationally designed structure (null substrates for dealkylation) can't be converted to cholesterol in wild-type worms, and their development was completely halted. This study underpins the essential function of DHCR24 in nematodes and would be beneficial for the development of novel nematocidal strategies.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2769-2777"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SMYD2 Imparts Gemcitabine Resistance to Pancreatic Adenocarcinoma Cells by Upregulating EVI2A.","authors":"Lei Jin, Daohai Qian, Xiaolei Tang, Yong Huang, Junwei Zou, Zhaoying Wu","doi":"10.1007/s12033-023-00908-7","DOIUrl":"10.1007/s12033-023-00908-7","url":null,"abstract":"<p><p>Although gemcitabine (GEM) is the first‑line drug for advanced pancreatic adenocarcinoma (PAAD), the development of GEM resistance severely limits the effectiveness of this chemotherapy. This study investigated the mechanisms of ecotropic viral integration site 2 A (EVI2A) for resistance to GEM and immune evasion in PAAD. GEM resistance-related biomarkers were predicted using GEO datasets, and GEM-resistant PAAD cells were generated. EVI2A was found expressed highly in GEM-resistant PAAD cells. Gain-of-function analyses revealed that EVI2A encouraged the proliferation and motility of GEM-resistant cells and prevented apoptosis. In addition, EVI2A reduced T cell effector activation. SMYD2 was overexpressed in GEM-resistant cells, and SMYD2 enhanced H3K36me2 modification of EVI2A, thereby promoting EVI2A expression. SMYD2 reduced the sensitivity of GEM-resistant cells, which was reversed by EVI2A knockdown. SMYD2 increased the amount of M2 macrophages (co-cultured with PAAD cells) and decreased T cell effector activation (co-cultured with macrophage supernatant), and the number of M2 macrophages was decreased and T cell effectors were activated following EVI2A knockdown. Our findings indicate that EVI2A, manipulated by the SMYD2-H3K36me2 epigenetic axis, promoted GEM resistance and M2 macrophage-mediated immune evasion in PAAD. Therefore, EVI2A might represent a therapeutic target for overcoming GEM resistance and immunosuppressive environment in PAAD.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2920-2933"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}