Journal of Gene Medicine最新文献

{"title":"In Silico Analysis of Novel circRNA-miRNA-mRNA Axis in BRAFV600E Melanoma: Implications for Primary to Metastasis Transformation and TIME Modulation","authors":"Hemangini Naik,&nbsp;Rajat Choudhary,&nbsp;V. Badireenath Konkimalla","doi":"10.1002/jgm.70023","DOIUrl":"https://doi.org/10.1002/jgm.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The BRAF^V600E mutation drives metastatic transition by altering the tumor immune microenvironment (TIME) through transcriptional and post-transcriptional regulation. Recent studies identify circular RNA (circRNA) and micro-RNA (miRNA) as key regulators in melanoma. This study uses <i>in silico</i> analysis to explore the circRNA-miRNA-mRNA axis in melanoma progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed primary (<i>n</i> = 42) and metastatic (<i>n</i> = 89) tumor samples from TCGA (SKCM), including their BRAF status, to identify markers in both tumor types and explored their association with immune cells within TIME. The key regulatory markers were verified using ROC curve analysis, IHC data from HPA database, and from an external dataset. Further, the circRNA-miRNA-mRNA axis was established using Cytoscape.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our comprehensive analysis identifies SYK, HMOX1, IL33, CFH, FGF1, COL8A1, and ADAMTS3 as the primary gene signatures, while VCAM-1 and SNAI2 dominate as prominent metastatic markers associated with BRAF^V600E and immune subtype. Among the immune infiltrating group, macrophages M1 and M2, CD8⁺ T-cells, and T_regs show a positive correlation with significant infiltration within TIME. We screened miRNA targets and circular sponges, built a circRNA-miRNA-mRNA network involving two circRNAs (hsa-circ-0011617 and hsa-circ-0011623) and three miRNAs (hsa-miR-1246, hsa-miR-346, and hsa-miR-1197) connected to the identified signature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, our study reveals two circRNAs that might have a potential role in primary to metastasis transition in the BRAF-mutated melanoma within TIME via the circRNA–miRNA–mRNA axis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171244","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}

{"title":"Sp2 Transcription Factor Alleviates Chondrocyte Loss in Osteoarthritis by Repressing the DVL1-Dependent Wnt/β-Catenin Signaling Pathway","authors":"Yuan Lin,&nbsp;Xinpeng Zheng,&nbsp;Xiaolei Chen,&nbsp;Yue Wang","doi":"10.1002/jgm.70021","DOIUrl":"https://doi.org/10.1002/jgm.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Osteoarthritis (OA) ranks as the most prevalent condition affecting the musculoskeletal system, where chondrocyte loss or dysfunction plays a crucial pathogenic role. This study is aimed at investigating key molecular cascades implicated in chondrocyte loss and cartilage injury in OA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A mouse model of OA was generated by destabilization of the medial meniscus. Histological staining was performed to evaluate the pathological changes in the knee joint tissue, the cartilage morphology, and the osteoblast population. A high-throughput sequencing analysis was performed to analyze aberrantly expressed genes in OA cartilage. Gain- or loss-of-function assays of dishevelled segment polarity protein 1 (DVL1) and Sp2 transcription factor (SP2) were carried out to analyze their effects on cartilage injury in mice and chondrocyte apoptosis in vitro. The interaction between SP2 and DVL1 was verified by chromatin immunoprecipitation and luciferase assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DVL1 was expressed at aberrantly high levels in the cartilage of OA mice. Its knockdown suppressed protein levels and transcriptional activity of β-catenin, thereby reducing cartilage damage and loss in mice. In vitro, chondrocyte apoptosis was inhibited upon DVL1 silencing. SP2, poorly expressed in OA cartilage, was found to repress DVL1 transcription by binding to its promoter. Overexpression of SP2 similarly alleviated cartilage injury and chondrocyte loss; however, these effects were negated by the additional DVL1 overexpression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that SP2 represses DVL1 transcription and inactivates the Wnt/β-catenin signaling, thus alleviating chondrocyte loss and cartilage injury in OA mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140490","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}

{"title":"Exploring the Links Between Micronutrients and Cardiac Traits: Roles of Vitamins A1, B9, and D","authors":"Lingwei Liu,&nbsp;Yongxi Cheng,&nbsp;Shujun Yan,&nbsp;Jian Zhou","doi":"10.1002/jgm.70022","DOIUrl":"https://doi.org/10.1002/jgm.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Micronutrients, such as vitamins and minerals, are essential for cardiac health, but their effects on cardiac structure and function remain unclear. This study aimed to investigate the causal impact of micronutrients on cardiac traits through Mendelian randomization (MR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A two-sample MR approach was employed to assess the causal effects between 14 micronutrients and 98 cardiac traits from various consortia and cohorts. Inverse variance-weighted (IVW) MR analyses were conducted, alongside a range of sensitivity analyses to confirm robustness. Both exposure and outcome populations were of European descent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant associations were found for Vitamins A1, B9, and D with various cardiac traits. Vitamin D was linked to reduced left ventricular end-diastolic myocardial wall thickness (IVW <i>β</i>: −0.16; 95% CI: −0.29 to −0.03; <i>p</i> = 0.01) and increased regional longitudinal and radial strains of the left ventricle (IVW <i>β</i>: 0.19; <i>p</i> = 0.03; IVW <i>β</i>: 0.17; <i>p</i> = 0.04). Vitamin A1 was associated with reduced left ventricular mass (IVW <i>β</i>: −10.23; <i>p</i> = 0.03; IVW <i>β</i>: −13.72; <i>p</i> = 0.007), both with and without body surface area and blood pressure adjustments. Vitamin B9 was associated with reductions in left ventricular mass (IVW <i>β</i>: −0.09; <i>p</i> = 0.04), myocardial wall thickness (IVW <i>β</i>: −0.13; <i>p</i> = 0.04), and ascending aorta maximum area (IVW <i>β</i>: −0.19; <i>p</i> = 0.01). No significant heterogeneity or horizontal pleiotropy was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Vitamins A1, B9, and D exhibit beneficial effects on cardiac structure and function, offering potential targets for nutritional intervention in at-risk populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118019","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}

{"title":"Identifying GAP43, NMU, and TEX29 as Potential Prognostic Biomarkers for COPD Combined With Lung Cancer Patients Using Machine Learning","authors":"Zhilong Xu,&nbsp;Kaiyao Zhang,&nbsp;Ao Zeng,&nbsp;Yanze Yin,&nbsp;KeYi Chen,&nbsp;Chao Wang,&nbsp;Xinyun Fang,&nbsp;Abudumijiti Abuduwayiti,&nbsp;JiaRui Wang,&nbsp;Jie Dai,&nbsp;Gening Jiang","doi":"10.1002/jgm.70020","DOIUrl":"https://doi.org/10.1002/jgm.70020","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic obstructive pulmonary disease (COPD) and lung cancer, frequently comorbid conditions intricately linked through smoking, represent significant global health challenges. COPD is a common comorbidity in nonsmall cell lung cancer (NSCLC) patients and has been shown to negatively impact prognosis. However, the molecular mechanisms underlying the interplay between COPD and lung cancer remain unclear. This study aims to identify differentially expressed genes (DEGs) associated with COPD-related lung cancer and, using various machine learning (ML) algorithms, uncover potential biomarkers for prognosis. We analyzed RNA sequencing data from 41 lung cancer patients (with and without COPD) and identified 61 DEGs, all of which were upregulated in solitary lung cancer compared to COPD-associated cases. Functional enrichment analysis revealed that these genes are involved in biological processes such as granulocyte chemotaxis and smooth muscle contraction and molecular functions including neuropeptide receptor binding. Three ML methods—support vector machine recursive feature elimination (SVM-RFE), least absolute shrinkage and selection operator (LASSO), and random forest—were applied to prioritize key biomarkers. Three genes, <i>GAP43</i>, <i>NMU</i>, and <i>TEX29</i>, were consistently selected across all methods. Further analysis demonstrated significant correlations between these genes and immune cell infiltration, with notable differences in immune cell composition observed in COPD-associated lung cancer. High expression levels of <i>GAP43</i>, <i>NMU</i>, and <i>TEX29</i> were associated with poor survival outcomes in lung cancer patients, as validated through survival analysis of TCGA database data. Our findings suggest that these genes may serve as diagnostic and prognostic biomarkers for COPD-related lung cancer, thereby providing insights into potential therapeutic targets. Further studies with larger cohorts are required to validate these results and elucidate the underlying molecular mechanisms.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100462","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}

{"title":"Natural Products as Modulators of miRNA in Hepatocellular Carcinoma: A Therapeutic Perspective","authors":"Shahzada Khalid Sohail","doi":"10.1002/jgm.70019","DOIUrl":"https://doi.org/10.1002/jgm.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) continues to pose a substantial worldwide health concern, marked by elevated mortality rates and restricted therapeutic alternatives. Recent studies have highlighted the potential of natural compounds as therapeutic agents in cancer management. This review focuses on the diagnostic and prognostic potential of microRNAs (miRNAs) as biomarkers in HCC, alongside the therapeutic promise of natural products. We explore the intricate role of miRNAs in the pathogenesis of HCC, detailing their regulatory functions in cellular processes such as proliferation, apoptosis, and metastasis. Additionally, we discuss the emerging evidence supporting the use of natural compounds, including phytochemicals, in modulating miRNA expression and their potential synergistic effects with conventional therapies. Key miRNAs discussed include miR-21, an oncogenic factor that promotes tumor growth by targeting the tumor suppressor phosphatase and tensin homolog (PTEN); miR-34a, which enhances apoptosis and may improve treatment efficacy when combined with c-MET inhibitors; miR-203, whose downregulation correlates with poor outcomes and may serve as a prognostic marker; miR-16, which acts as a tumor suppressor and has diagnostic potential when measured alongside traditional markers like alpha-fetoprotein (AFP); and miR-483-3p, associated with resistance to apoptosis and tumor progression. By integrating insights from recent studies, this review aims to highlight the dual role of miRNAs as both biomarkers and therapeutic targets, paving the way for enhanced diagnostic strategies and novel treatment modalities in HCC management.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883931","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}

{"title":"Adoptive Transfer of T Cells as a Potential Therapeutic Approach in the Bleomycin-Injured Mouse Lung","authors":"Seyran Mutlu,&nbsp;Kleanthis Fytianos,&nbsp;Céline Ferrié,&nbsp;Melanie Scalise,&nbsp;Sofia Mykoniati,&nbsp;Amiq Gazdhar,&nbsp;Fabian Blank","doi":"10.1002/jgm.70018","DOIUrl":"https://doi.org/10.1002/jgm.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Idiopathic pulmonary fibrosis (IPF) is a lethal disease with an unknown etiology and complex pathophysiology that are not fully understood. The disease involves intricate cellular interplay, particularly among various immune cells. Currently, there is no treatment capable of reversing the fibrotic process or aiding lung regeneration. Hepatocyte growth factor (HGF) has demonstrated antifibrotic properties, whereas the adoptive transfer of modified T cells is a well-established treatment for various malignancies. We aimed to understand the dynamics of T cells in the progression of lung fibrosis and to study the therapeutic benefit of adoptive T cell transfer in a bleomycin-injured mouse lung (BLM) model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>T cells were isolated from the spleen of naïve mice and transfected in vitro with mouse HGF plasmid and were administered intratracheally to the mice lungs 7 days post-bleomycin injury to the lung. Lung tissue and bronchoalveolar lavage were collected and analyzed using flow cytometry, histology, qRT-PCR, ELISA, and hydroxyproline assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings demonstrate the successful T cell therapy of bleomycin-induced lung injury through the adoptive transfer of HGF-transfected T cells in mice. This treatment resulted in decreased collagen deposition and a balancing of immune cell exhaustion and cytokine homeostasis compared with untreated controls. In vitro testing showed enhanced apoptosis in myofibroblasts induced by HGF-overexpressing T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Taken together, our data highlight the great potential of adoptive T cell transfer as an emerging therapy to counteract lung fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741678","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}

{"title":"USF2-Mediated Transcription of BZW2 Contributes to CRC Malignant Progression by Affecting LAMP3","authors":"Xintao Li,&nbsp;Yizhi Liu,&nbsp;Shuang Liu,&nbsp;Nanzheng Chen","doi":"10.1002/jgm.70016","DOIUrl":"10.1002/jgm.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal cancer (CRC) is one of the most frequent causes of cancer death in China, and its occurrence, development, and prognosis are closely related to the living state of patients. Basic leucine zipper and W2 domains 2 (BZW2), also known as eIF5-mimin protein 1 (5MP1), is a translational regulatory protein and highly expressed in CRC and promotes malignant progression of CRC, but the specific mechanism has not been clarified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The databases were used to mine related genes. The expression levels of genes were detected by quantitative real-time PCR (qRT-PCR) and western blot. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry, transwell assay, and sphere formation assay were employed to examine the effects of BZW2 on the phenotypes in CRC cells in vitro. The mechanism of BZW2 in CRC progression was determined by chromatin immunoprecipitation (CHIP) and dual luciferase reporter assay. In vivo, xenograft animal model was performed to verify the results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BZW2 was elevated in CRC tissues and cells and was associated with poor prognosis of patients. Functionally, BZW2 enhanced CRC cell proliferation, invasion, and sphere formation but restrained apoptosis. CHIP and dual luciferase reporter assay confirmed that upstream transcription factor 2 (USF2) regulated BZW2 transcription. Also, BZW2 could attenuate the effects of USF2 defection in CRC progression. Meanwhile, lysosomal associated membrane protein 3 (LAMP3) acted as the target of BZW2 and restored the action of BZW2 knockdown. Similarly, BZW2 was involved in tumorigenesis in vivo by the same mechanism in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings revealed a molecular basis for BZW2's promotion of CRC malignant progression and highlighted the role of BZW2 in promoting cancer stemness.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671743","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}

{"title":"PYCR1 Promotes Esophageal Squamous Cell Carcinoma by Interacting With EGFR to Affecting the PI3K/Akt/mTOR Signaling Pathway","authors":"Yu-Qi Meng,&nbsp;Hai-Ming Feng,&nbsp;Bin Li,&nbsp;Yuan Xie,&nbsp;Zheng Li,&nbsp;Zhen-Qing Li,&nbsp;Xuan Li","doi":"10.1002/jgm.70017","DOIUrl":"https://doi.org/10.1002/jgm.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The expression and functional role of pyrroline-5-carboxylate reductase 1 (PYCR1) in esophageal squamous cell carcinoma (ESCC) remain poorly understood. This study aimed to elucidate the role and underlying mechanisms of PYCR1 in ESCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilized an ESCC tissue microarray coupled with immunohistochemical staining to assess variability in PYCR1 protein expression among ESCC patients and evaluate its clinical relevance. PYCR1 was silenced in ESCC cell lines with short hairpin RNA (shRNA), followed by functional assays (colony formation, caspase 3/7 activity, methylthiazol tetrazolium, wound healing, and migration/invasion assays) to evaluate its role in ESCC progression. In vivo, mouse tumor xenograft models were used to examine PYCR1's impact on tumor growth. To identify downstream targets and pathways, we conducted coimmunoprecipitation, mass spectrometry, immunofluorescence, and proteomic analyses, validated by western blotting and rescue experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings demonstrated a consistent upregulation of PYCR1 in ESCC tissues. Both in vitro and in vivo studies revealed that PYCR1 suppression significantly inhibited ESCC progression, impacting key processes such as proliferation, apoptosis, migration, and invasion. Mechanistically, PYCR1 was shown to interact with EGFR, promoting ESCC progression and metastasis by activating the PI3K/AKT/mTOR signaling pathways, which are integral to the aggressive behavior of the disease. Rescue experiments further confirmed that EGFR overexpression effectively reversed the inhibitory effects of PYCR1 knockdown in ESCC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights the critical role of PYCR1 in driving ESCC progression and metastasis, underscoring its potential as a promising therapeutic target for managing this malignancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646032","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}

{"title":"Integrated Single-Cell Transcriptome and eQTL Analyses Reveal the Role of PZP in Aging and Chronic Kidney Disease","authors":"Xinhui Huang,&nbsp;Cheng Zhu,&nbsp;Shiqi Lv,&nbsp;Yulin Wang,&nbsp;Jiayi Wang,&nbsp;Shuangxin Yuan,&nbsp;Yue Yang,&nbsp;Xiaoqiang Ding,&nbsp;Xiaoyan Zhang","doi":"10.1002/jgm.70015","DOIUrl":"https://doi.org/10.1002/jgm.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Aging is a known driver of chronic kidney disease (CKD), yet the genetic mechanisms linking these two conditions remain unclear. This study aims to explore the role of CD8+ central memory T (T_CM) cells and their associated gene expression in the interaction between aging and CKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood samples from young controls, elderly individuals, and CKD patients were analyzed using single-cell RNA sequencing to investigate immune cell populations. Expression quantitative trait loci (eQTL) and Mendelian randomization analyses were performed using data from genomic cohorts, including the UK Biobank and FinnGen, to assess causal relationships. Experimental validation evaluated correlations between pregnancy zone protein (PZP) expression and clinical indicators such as age, glomerular filtration rate (GFR), serum creatinine, and proteinuria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Increased proportions of CD8+ T_CM cells were observed in elderly individuals and CKD patients. PZP was identified as a key genetic factor in CKD progression and aging, linked to metabolic reprogramming and impaired intercellular communication. PZP expression correlated significantly with aging (<i>r</i> = 0.818, <i>p</i> = 0.047), reduced GFR (<i>r</i> = −0.557, <i>p</i> = 0.011), elevated serum creatinine (<i>r</i> = 0.507, <i>p</i> = 0.019), and proteinuria (<i>r</i> = 0.761, <i>p</i> = 0.047).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Shared genetic and immunological mechanisms link CKD and aging, with CD8+ T_CM cells contributing to immune dysregulation and chronic inflammation. The dual role of PZP, involving its upregulation, disrupted immune communication, and metabolic reprogramming, highlights its potential as a biomarker and therapeutic target for aging-associated kidney diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581421","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}

{"title":"Characterization of Immune Landscape Based on Homologous Recombination Deficiency Associated Signatures and Identification of Knockdown of ERCC6L to Promote Radiosensitivity in Breast Cancer","authors":"Jiahao Li,&nbsp;Chen Gong,&nbsp;Haiting Zhou,&nbsp;Junxia Liu,&nbsp;Wentao Ha,&nbsp;Yizhi Jiang,&nbsp;Huihua Xiong","doi":"10.1002/jgm.70012","DOIUrl":"https://doi.org/10.1002/jgm.70012","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;Homologous recombination deficiency (HRD) exhibits significant associations with the occurrence, progression, and prognosis of breast cancer. However, the primary breast cancer HRD positivity rate is merely 24%. The identification of markers associated with HRD is crucial for the development of novel therapeutic approaches for breast cancer. The role of the oncogene &lt;i&gt;ERCC6L&lt;/i&gt; in breast cancer remains unclear, and its interaction with radiotherapy has yet to be explored, necessitating further investigation for clarification.&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 employed WGCNA to identify genes associated with the HRD score, utilizing public HRD score and genetic data from TCGA breast cancer, with their clinical characteristics. Subsequently, we employed various machine learning methods to filter relevant genes. The final four genes were obtained through random forest and stepCox, and their performance was validated in TCGA, GSE96058, and METABRIC datasets. Next, we assessed the tumor immune microenvironment using methods such as ssGSEA, GSVA, CIBERSORT, ESTIMATE, and single-cell analysis. Finally, we validated the downregulation of &lt;i&gt;ERCC6L&lt;/i&gt;, increasing DNA damage and enhancing radiation sensitivity, through immune fluorescence, flow cytometry, plate cloning, and western blot.&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;A prognostic model named HRAS was established through machine learning, consisting of four genes (&lt;i&gt;ERCC6L&lt;/i&gt;, &lt;i&gt;UBE2T&lt;/i&gt;, &lt;i&gt;TPX2&lt;/i&gt;, and &lt;i&gt;SLC7A5&lt;/i&gt;). The indicator exhibited excellent predictive performance on the prognosis and the efficacy of immunotherapy and radiotherapy of breast cancer patients in independent datasets. Breast cancer patients with high HRAS scores showed higher TMB and stemness, increased expression of immune checkpoints, reduced immune cell infiltration, and poorer prognosis in the context of immunotherapy and radiotherapy. Experimental validation demonstrated that knockdown of ERCC6L markedly elevated DNA damage, enhanced apoptosis, and induced cell cycle arrest in response to radiation therapy, thereby sensitizing cells to radiation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The HRD-related signatures displayed strong predictive capabilities for the prognosis in multiple datasets and the efficacy of immunotherapy and radiotherapy of breast cancer patients. Moreover, the composite indicator reflected the immune microenvironment characteristics and could be novel markers for predicting the prognosis and clinical treatment outcomes in breast cancer patients. Our experiments first elucidated the role of &lt;i&gt;ERCC6L&lt;/i&gt; i","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475681","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}