Journal of Gene Medicine最新文献

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Exploration of YBX1 role in the prognostic value and immune characteristics by single-cell and bulk sequencing analysis for liver hepatocellular carcinoma 通过单细胞和批量测序分析探讨 YBX1 在肝肝细胞癌预后价值和免疫特征中的作用
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-03-06 DOI: 10.1002/jgm.3680
Qingqing Zhang, Bingye Zhu, Hongyan Yang, Fei Li, Ying Qu, Lungen Lu, Qidi Zhang
{"title":"Exploration of YBX1 role in the prognostic value and immune characteristics by single-cell and bulk sequencing analysis for liver hepatocellular carcinoma","authors":"Qingqing Zhang,&nbsp;Bingye Zhu,&nbsp;Hongyan Yang,&nbsp;Fei Li,&nbsp;Ying Qu,&nbsp;Lungen Lu,&nbsp;Qidi Zhang","doi":"10.1002/jgm.3680","DOIUrl":"10.1002/jgm.3680","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Y-box binding protein 1 (YBX1) plays a variety of roles in progression of multiple tumors. However, the role of YBX1 in prognostic value and immune regulation for liver hepatocellular carcinoma (LIHC) remains unclear. The present study aimed to examine the effect of YBX1 on the regulation of tumor immunity and survival prediction in LIHC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>YBX1-related expression profiles and single-cell and bulk sequencing analysis were performed using online databases. YBX1 expression was validated by a quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry. Univariate/multivariate Cox regression analysis was performed to determine independent predictors of overall survival (OS). The ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis were used to assess the relationships between YBX1 and LIHC immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>YBX1 was over-expressed in LIHC tissues and cell lines. High YBX1 expression was significantly associated with poor OS. Univariate/multivariate Cox regression analysis revealed that YBX1 was an independent prognostic factor for LIHC. Gene set enrichment analysis revealed that YBX1 was associated with multiple signaling pathways correlated to LIHC. Additionally, YBX1 was expressed in multiple immune cells and was significantly correlated with immune cells, immune checkpoint markers and tumor immune microenvironment. The TIDE analysis demonstrated that LIHC patients with high YBX1 expression showed a higher T-cell dysfunction score and a higher exclusion score, as well as poorer immunotherapy response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>YBX1 plays crucial oncogenic roles in LIHC and is closely associated with the immune defense system. YBX1 inhibition may serve as a potential treatment for LIHC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SPINK5 inhibits esophageal squamous cell carcinoma metastasis via immune activity SPINK5通过免疫活性抑制食管鳞状细胞癌转移
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-03-05 DOI: 10.1002/jgm.3667
Jie Chen, Juncheng Lu, Zhiqiang Chen, Zihao Liu, Yuejun Sun, Shuyan He, Yedong Mi, Yi Gao, Dong Shen, Qingfeng Lin
{"title":"SPINK5 inhibits esophageal squamous cell carcinoma metastasis via immune activity","authors":"Jie Chen,&nbsp;Juncheng Lu,&nbsp;Zhiqiang Chen,&nbsp;Zihao Liu,&nbsp;Yuejun Sun,&nbsp;Shuyan He,&nbsp;Yedong Mi,&nbsp;Yi Gao,&nbsp;Dong Shen,&nbsp;Qingfeng Lin","doi":"10.1002/jgm.3667","DOIUrl":"10.1002/jgm.3667","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of esophageal cancer with relatively high mortality worldwide. Serine peptidase inhibitor Kazal-type 5 (SPINK5) is reported to be downregulated in ESCC. However, its explicit role in ESCC remains further investigation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The tumor tissues and adjacent non-cancerous tissues were obtained from 196 patients with ESCC for the determination of &lt;i&gt;SPINK5&lt;/i&gt; mRNA levels. Additionally, the relationship between &lt;i&gt;SPINK5&lt;/i&gt; mRNA levels and clinicopathological features of ESCC patients was explored. The effects of &lt;i&gt;SPINK5&lt;/i&gt; on the invasion and migration of ESCC cells were assessed using Transwell assays. Furthermore, &lt;i&gt;SPINK5&lt;/i&gt; mRNA and LEKTI protein were measured in ESCC cell lines after treatment with poly (I:C), lipopolysaccharide (LPS) or unmethylated CpG DNA. Moreover, the correlation between expression of &lt;i&gt;SPINK5&lt;/i&gt; and nuclear factor-kappa B (NF-κB) signaling pathway-related genes was analyzed in the TCGA-ESCC cohort, and the effects of &lt;i&gt;SPINK5&lt;/i&gt; on NF-κB transcription was analyzed using a luciferase reporter gene assay. Finally, the correlations between &lt;i&gt;SPINK5&lt;/i&gt; and infiltration of immune cells, immune scores, stromal scores and ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) scores were explored.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;&lt;i&gt;SPINK5&lt;/i&gt; mRNA levels were downregulated in tumor tissues, which was significantly correlated with higher lymph node metastases. Overexpressed &lt;i&gt;SPINK5&lt;/i&gt; inhibited cell invasion and migration in ESCC cell lines. Mechanistically, LPS-induced activation of Toll-like receptor 4 (TLR4) decreased &lt;i&gt;SPINK5&lt;/i&gt; mRNA and LEKTI in KYSE150 and KYSE70 cells. Spearman correlation analysis revealed that &lt;i&gt;SPINK5&lt;/i&gt; mRNA was significantly negatively correlated with a total of seven NF-κB signaling pathway-related genes in TCGA-ESCC patients. Moreover, downregulation of &lt;i&gt;SPINK5&lt;/i&gt; increased and upregulation of &lt;i&gt;SPINK5&lt;/i&gt; decreased the activity of the NF-κB promoter in HEK293T cells. Finally, immune cells infiltration analysis revealed that &lt;i&gt;SPINK5&lt;/i&gt; was significantly correlated with the infiltration of various immune cells, stromal scores, immune scores and ESTIMATE scores.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;&lt;i&gt;SPINK5&lt;/i&gt; plays critical roles in the TLR4/NF-κB pathway and immune cells infiltration, which might contribute to the ESCC metastasis. The findings of the present study may provide a promising biomarker for the diagnosis and treatment of esop","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of a novel prognostic signature based on single-cell combined bulk RNA analysis in breast cancer 基于乳腺癌单细胞联合大体 RNA 分析的新型预后特征的开发。
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-02-25 DOI: 10.1002/jgm.3673
Ying Xiao, Ge Hu, Ning Xie, Liang Yin, Yaqiang Pan, Cong Liu, Shihan Lou, Cunzhi Zhu
{"title":"Development of a novel prognostic signature based on single-cell combined bulk RNA analysis in breast cancer","authors":"Ying Xiao,&nbsp;Ge Hu,&nbsp;Ning Xie,&nbsp;Liang Yin,&nbsp;Yaqiang Pan,&nbsp;Cong Liu,&nbsp;Shihan Lou,&nbsp;Cunzhi Zhu","doi":"10.1002/jgm.3673","DOIUrl":"10.1002/jgm.3673","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Breast cancer (BC), a malignant tumor, is a significant cause of death and disability among women globally. Recent research indicates that copy number variation plays a crucial role in tumor development. In this study, we employed the Single-Cell Variational Aneuploidy Analysis (SCEVAN) algorithm to differentiate between malignant and non-malignant cells, aiming to identify genetic signatures with prognostic relevance for predicting patient survival.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We analyzed gene expression profiles and associated clinical data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Using the SCEVAN algorithm, we distinguished malignant from non-malignant cells and investigated cellular interactions within the tumor microenvironment (TME). We categorized TCGA samples based on differentially expressed genes (DEGs) between these cell types. Subsequent Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted. Additionally, we developed polygenic models for the DEGs using least absolute shrinkage and selection operator-penalized Cox regression analysis. To assess the prognostic accuracy of these characteristics, we generated Kaplan–Meier and receiver operating characteristic curves from training and validation datasets. We also monitored the expression variations of prognostic genes across the pseudotime of malignant cells. Patients were divided into high-risk and low-risk groups based on median risk scores to compare their TME and identify potential therapeutic agents. Lastly, polymerase chain reaction was used to validate seven pivotal genes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The SCEVAN algorithm identified distinct malignant and non-malignant cells in GSE180286. Cellchat analysis revealed significantly increased cellular communication, particularly between fibroblasts, endothelial cells and malignant cells. The DEGs were predominantly involved in immune-related pathways. TCGA samples were classified into clusters A and B based on these genes. Cluster A, enriched in immune pathways, was associated with poorer prognosis, whereas cluster B, predominantly involved in circadian rhythm pathways, showed better outcomes. We constructed a 14-gene prognostic signature, validated in a 1:1 internal TCGA cohort and external GEO datasets (GSE42568 and GSE146558). Kaplan–Meier analysis confirmed the prognostic signature's accuracy (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Receiver operating characteristic curve analysis demonstrated the predictive reliability of these prognostic features. Single-cell pseudotime analysis with monocle2 highlighted the distinct expression trends of these genes in malignant cells, undersco","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Global analysis of urinary extracellular vesicle small RNAs in autosomal dominant polycystic kidney disease 常染色体显性多囊肾中尿细胞外囊泡小 RNA 的总体分析
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-02-25 DOI: 10.1002/jgm.3674
Hamad Ali, Md. Zubbair Malik, Mohamed Abu-Farha, Jehad Abubaker, Preethi Cherian, Rasheeba Nizam, Sindhu Jacob, Yousif Bahbahani, Medhat Naim, Sajjad Ahmad, Mohammad Al-Sayegh, Thangavel Alphonse Thanaraj, Albert C. M. Ong, Peter C. Harris, Fahd Al-Mulla
{"title":"Global analysis of urinary extracellular vesicle small RNAs in autosomal dominant polycystic kidney disease","authors":"Hamad Ali,&nbsp;Md. Zubbair Malik,&nbsp;Mohamed Abu-Farha,&nbsp;Jehad Abubaker,&nbsp;Preethi Cherian,&nbsp;Rasheeba Nizam,&nbsp;Sindhu Jacob,&nbsp;Yousif Bahbahani,&nbsp;Medhat Naim,&nbsp;Sajjad Ahmad,&nbsp;Mohammad Al-Sayegh,&nbsp;Thangavel Alphonse Thanaraj,&nbsp;Albert C. M. Ong,&nbsp;Peter C. Harris,&nbsp;Fahd Al-Mulla","doi":"10.1002/jgm.3674","DOIUrl":"10.1002/jgm.3674","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic renal disease progressing to end-stage renal disease. There is a pressing need for the identification of early ADPKD biomarkers to enable timely intervention and the development of effective therapeutic approaches. Here, we profiled human urinary extracellular vesicles small RNAs by small RNA sequencing in patients with ADPKD and compared their differential expression considering healthy control individuals to identify dysregulated small RNAs and analyze downstream interaction to gain insight about molecular pathophysiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a cross-sectional study where urine samples were collected from a total of 23 PKD1-ADPKD patients and 28 healthy individuals. Urinary extracellular vesicles were purified, and small RNA was isolated and sequenced. Differentially expressed Small RNA were identified and functional enrichment analysis of the critical miRNAs was performed to identify driver genes and affected pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>miR-320b, miR-320c, miR-146a-5p, miR-199b-3p, miR-671-5p, miR-1246, miR-8485, miR-3656, has_piR_020497, has_piR_020496 and has_piR_016271 were significantly upregulated in ADPKD patient urine extracellular vesicles and miRNA-29c was significantly downregulated. Five ‘driver’ target genes (<i>FBRS</i>, <i>EDC3</i>, <i>FMNL3</i>, <i>CTNNBIP1</i> and <i>KMT2A</i>) were identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings of the present study make significant contributions to the understanding of ADPKD pathogenesis and to the identification of novel biomarkers and potential drug targets aimed at slowing disease progression in ADPKD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3674","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
JAM2 is a prognostic biomarker and inhibits proliferation, metastasis and epithelial–mesenchymal transition in lung adenocarcinoma JAM2 是一种预后生物标志物,可抑制肺腺癌的增殖、转移和上皮-间质转化。
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-02-25 DOI: 10.1002/jgm.3679
Yanxin Dong, Jiale Zhang, Shun Xie, Shouyin Di, Boshi Fan, Taiqian Gong
{"title":"JAM2 is a prognostic biomarker and inhibits proliferation, metastasis and epithelial–mesenchymal transition in lung adenocarcinoma","authors":"Yanxin Dong,&nbsp;Jiale Zhang,&nbsp;Shun Xie,&nbsp;Shouyin Di,&nbsp;Boshi Fan,&nbsp;Taiqian Gong","doi":"10.1002/jgm.3679","DOIUrl":"10.1002/jgm.3679","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Junctional adhesion molecule 2 (JAM2) plays a pivotal role in various biological processes, including proliferation, metastasis and angiogenesis, contributing to tumor progression. While previous studies have highlighted the polarizing functions of JAM2 in different cancer types, its specific role in lung adenocarcinoma (LUAD) remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we harnessed multiple public databases to analyze the expression and prognostic significance of JAM2 in LUAD. Using the Linkedomics database, Matescape database and R package, we explored the associated genes, the potential biological functions and the impact of JAM2 on the tumor microenvironment. Our findings from public databases were further validated using real-time quantitative PCR, western blot and immunohistochemistry. Additionally, <i>in vitro</i> experiments were conducted to assess the influence of JAM2 on LUAD cell proliferation, invasion, migration, apoptosis and epithelial–mesenchymal transition. Furthermore, we established a xenograft model to investigate the <i>in vivo</i> effects of JAM2 on tumorigenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results revealed a significant downregulation of JAM2 in LUAD, and patients with low JAM2 expression exhibited unfavorable overall survival outcomes. Functional enrichment analysis indicated that JAM2 may be associated with processes such as cell adhesion, extracellular matrix, cell junctions and regulation of proliferation. Notably, increased JAM2 expression correlated with higher tumor microenvironment scores and reduced immune cell abundance. Furthermore, overexpression of JAM2 induced apoptosis, suppressed tumor proliferation and exhibited potential inhibitory effects on tumor invasion and migration through the modulation of epithelial–mesenchymal transition. Additionally, <i>in vivo</i> experiments confirmed that JAM2 overexpression led to a reduction in tumor growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, our study highlights the clinical significance of low JAM2 expression as a predictor of poor prognosis in LUAD patients. Moreover, JAM2 was found to exert inhibitory effects on various aspects of tumor progression. Consequently, JAM2 emerges as a promising prognostic biomarker and a potential therapeutic target for LUAD patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circulating microvesicles miR139-3p from bronchopulmonary dysplasia aggravates pulmonary vascular simplification by targeting 4E binding protein 1 来自支气管肺发育不良的循环微囊miR139-3p通过靶向4E结合蛋白1加重肺血管简化。
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-02-22 DOI: 10.1002/jgm.3675
Linchao Yu, Rui He, Chan Liu, Yuan Shi, Daoxin Wang
{"title":"Circulating microvesicles miR139-3p from bronchopulmonary dysplasia aggravates pulmonary vascular simplification by targeting 4E binding protein 1","authors":"Linchao Yu,&nbsp;Rui He,&nbsp;Chan Liu,&nbsp;Yuan Shi,&nbsp;Daoxin Wang","doi":"10.1002/jgm.3675","DOIUrl":"10.1002/jgm.3675","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Microvesicles (MVs) play a crucial role in bronchopulmonary dysplasia (BPD). There are many MVs in circulating plasma, and they are in direct contact with lung endothelial cells. However, the molecular mechanism and causative effect of circulating MVs on BPD remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical plasma samples were collected, circulating MVs were isolated, and microRNA (miRNA) sequencing was performed. The BPD model was established, and different MVs were administered. Alveoli and pulmonary vessels were examined by hematoxylin–eosin staining, and body weight and length were measured. <i>In vitro</i>, gene expression was disrupted by miRNA mimics, miRNA inhibitors or plasmid transfection. Cell proliferation and protein expression were detected by cell scratch assay, accurate 5-ethynyl-2-deoxyuridine test, western blotting, or immunofluorescence assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BPD-derived MVs further aggravated pulmonary vascular simplification, while circulating MVs from control mice mitigated pulmonary vascular simplification. Micro-RNA sequencing and independent sample verification revealed that miR139-3p, but not miR6125 or miR193b-3p, was the most critical effector molecule in MVs. Mechanism studies showed that eukaryotic translation initiation factor 4E binding protein 1 was the target gene for miR139-3p. In addition, we found that supplementation of miR139-3p inhibitor partially alleviated pulmonary vascular simplification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results indicate that circulating MVs are involved in forming BPD by carrying miR139-3p molecules and support miR139-3p inhibitors as a potential therapeutic strategy for alleviating pulmonary vascular simplification in BPD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Baicalin induces ferroptosis in oral squamous cell carcinoma by suppressing the activity of FTH1 黄芩苷通过抑制 FTH1 的活性诱导口腔鳞状细胞癌的铁变态反应
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-02-21 DOI: 10.1002/jgm.3669
Zhihao Wen, Yuxiao Zhang, Bo Gao, Xin Chen
{"title":"Baicalin induces ferroptosis in oral squamous cell carcinoma by suppressing the activity of FTH1","authors":"Zhihao Wen,&nbsp;Yuxiao Zhang,&nbsp;Bo Gao,&nbsp;Xin Chen","doi":"10.1002/jgm.3669","DOIUrl":"10.1002/jgm.3669","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study investigated the role of the ferroptosis-related gene FTH1 in oral squamous cell carcinoma (OSCC) and evaluated the therapeutic potential of baicalin in OSCC cell treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prognostic model was established by bioinformatic analysis, consisting of 12 ferroptosis related genes (FRGs), and FTH1 was selected as the most significantly up-regulated FRGs. The clinical correlation of FTH1 in OSCC samples was evaluated by both immunohistochemical and bioinformatic characterizations. The effects of FTH1 on migration, invasion, epithelial–mesenchymal transition (EMT) and proliferation were determined by wound healing assays, transwell assays, western blotting and 5′-ethynl 2′-deoxyuridine proliferation assays, respectively. The effects of FTH1 on ferroptosis were tested via ferroptosis markers and Mito Tracker staining. In addition, the therapeutic effects of baicalin on OSCC cells were confirmed using EMT, migration, invasion, proliferation and ferroptosis assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 12 FRGs were predictive of the prognosis for OSCC patients, and FTH1 expression was identified as significantly up-regulated in OSCC samples, which was highly associated with survival, immune cell infiltration and drug sensitivity. Moreover, knocking down FTH1 inhibited cell proliferation, EMT and invasive phenotypes, but induced ferroptosis in OSCC cells (Cal27 and SCC25). Furthermore, baicalin directly suppressed expression of FTH1 in OSCC cells, and effectively promoted ferroptosis and inhibited the proliferation as well as EMT by directly targeting FTH1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study has demonstrated that FTH1 is a therapeutic target for OSCC treatment, and has provided evidence that baicalin offers a promising alternative for OSCC treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139914145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zebrafish in understanding molecular pathophysiology, disease modeling, and developing effective treatments for Rett syndrome 斑马鱼在了解分子病理生理学、疾病建模和开发有效治疗 Rett 综合症方面的作用。
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-02-21 DOI: 10.1002/jgm.3677
Subrata Pramanik, Asis Bala, Ajay Pradhan
{"title":"Zebrafish in understanding molecular pathophysiology, disease modeling, and developing effective treatments for Rett syndrome","authors":"Subrata Pramanik,&nbsp;Asis Bala,&nbsp;Ajay Pradhan","doi":"10.1002/jgm.3677","DOIUrl":"10.1002/jgm.3677","url":null,"abstract":"<p>Rett syndrome (RTT) is a rare but dreadful X-linked genetic disease that mainly affects young girls. It is a neurological disease that affects nerve cell development and function, resulting in severe motor and intellectual disabilities. To date, no cure is available for treating this disease. In 90% of the cases, RTT is caused by a mutation in methyl-CpG-binding protein 2 (MECP2), a transcription factor involved in the repression and activation of transcription. MECP2 is known to regulate several target genes and is involved in different physiological functions. Mouse models exhibit a broad range of phenotypes in recapitulating human RTT symptoms; however, understanding the disease mechanisms remains incomplete, and many potential RTT treatments developed in mouse models have not shown translational effectiveness in human trials. Recent data hint that the zebrafish model emulates similar disrupted neurological functions following mutation of the <i>mecp2</i> gene. This suggests that zebrafish can be used to understand the onset and progression of RTT pathophysiology and develop a possible cure. In this review, we elaborate on the molecular basis of RTT pathophysiology in humans and model organisms, including rodents and zebrafish, focusing on the zebrafish model to understand the molecular pathophysiology and the development of therapeutic strategies for RTT. Finally, we propose a rational treatment strategy, including antisense oligonucleotides, small interfering RNA technology and induced pluripotent stem cell-derived cell therapy.</p>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139914147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trends in the synthetic polymer delivery of RNA 合成聚合物输送 RNA 的趋势。
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-02-21 DOI: 10.1002/jgm.3672
Josh J. Friesen, Anna K. Blakney
{"title":"Trends in the synthetic polymer delivery of RNA","authors":"Josh J. Friesen,&nbsp;Anna K. Blakney","doi":"10.1002/jgm.3672","DOIUrl":"10.1002/jgm.3672","url":null,"abstract":"<p>Ribonucleic acid (RNA) has emerged as one of the most promising therapeutic payloads in the field of gene therapy. There are many unique types of RNA that allow for a range of applications including vaccination, protein replacement therapy, autoimmune disease treatment, gene knockdown and gene editing. However, RNA triggers the host immune system, is vulnerable to degradation and has a low proclivity to enter cells spontaneously. Therefore, a delivery vehicle is required to facilitate the protection and uptake of RNA therapeutics into the desired host cells. Lipid nanoparticles have emerged as one of the only clinically approved vehicles for genetic payloads, including in the COVID-19 messenger RNA vaccines. While lipid nanoparticles have distinct advantages, they also have drawbacks, including strong immune stimulation, complex manufacturing and formulation heterogeneity. In contrast, synthetic polymers are a widely studied group of gene delivery vehicles and boast distinct advantages, including biocompatibility, tunability, inexpensiveness, simple formulation and ease of modification. Some classes of polymers enhance efficient transfection efficiency, and lead to lower stimulation of the host immune system, making them more viable candidates for non-vaccine-related applications of RNA medicines. This review aims to identify the most promising classes of synthetic polymers, summarize recent research aimed at moving them into the clinic and postulate the future steps required for unlocking their full potential.</p>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139914146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Natural killer cell-based signature: Prognostic analysis in head and neck squamous cell carcinoma 基于自然杀伤细胞的特征:头颈部鳞状细胞癌的预后分析。
IF 3.5 4区 医学
Journal of Gene Medicine Pub Date : 2024-02-21 DOI: 10.1002/jgm.3671
Zizhao Guo, Yuxia Zhao, Meng Xu, Long Zhao, Xiaolei Wang
{"title":"Natural killer cell-based signature: Prognostic analysis in head and neck squamous cell carcinoma","authors":"Zizhao Guo,&nbsp;Yuxia Zhao,&nbsp;Meng Xu,&nbsp;Long Zhao,&nbsp;Xiaolei Wang","doi":"10.1002/jgm.3671","DOIUrl":"10.1002/jgm.3671","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Head and neck squamous cell carcinoma (HNSC) is a challenging cancer with significant clinical implications. Natural killer (NK) cells have emerged as important players in tumor immunosurveillance, yet their role and potential as prognostic biomarkers in HNSC remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Quantitative analysis using multiple algorithms identified FCRL1, KIR3DL2 and ZNF541 as molecules significantly associated with local NK cell infiltration and patient survival. A prognostic model based on these molecules demonstrated robust predictive performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analysis of high- and low-risk patient groups revealed distinct differences in the tumor microenvironment, indicating an inhibitory immune microenvironment in high-risk patients. Notably, low-risk patients exhibited potential sensitivity to immunotherapy and showed favorable responses to specific drugs such as axitinib, methotrexate, rapamycin and vorinostat. NK cells, important effectors of the innate immune response, were found to play a crucial role in HNSC immunity. The present study provides valuable insights into the correlation between FCRL1, KIR3DL2, ZNF541 and NK cell infiltration, paving the way for future investigations into their roles in HNSC. Activation of NOTCH signaling, MYC targets, DNA repair, E2F targets, epithelial–mesenchymal transition, G2M checkpoint and mitotic spindle pathways in high-risk patients suggests their involvement in disease progression and poor prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The present study reveals the significance of NK cells in HNSC and their potential as prognostic biomarkers. The CFKZ score offers a promising approach for predicting patient outcomes and guiding personalized treatment decisions in HNSC. These findings contribute to our understanding of HNSC immunobiology and hold implications for precision medicine in HNSC management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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