This study aims to investigate the phenotypes, mutation types, and loci associated with TP63-related syndrome by focusing on an affected proband.
Methods
Employing a proband collection strategy, we identified a family presenting with TP63-related syndrome and performed thorough clinical evaluations on the proband and family members. We subsequently documented the phenotype, mutation type, and locus of the TP63 gene, followed by Sanger DNA sequencing analysis.
Results
We identified a family affected by TP63-related syndrome. The proband, a young adult male, demonstrated congenital anodontia, hypohidrosis, sparse hair, and additional features characteristic of ectodermal dysplasia. Further clinical manifestations included left ear hearing impairment, cleft lip/palate, hypospadias, and syndactyly. Sequencing analysis revealed a missense nucleotide variant (c.184G>C, p.Val62Leu) in exon 2 of the TP63 gene. This variant was absent from established SNP databases and was not detected in other family members or unrelated healthy individuals.
Conclusions
The family exhibits significant symptoms consistent with TP63 syndrome. The identified missense mutation is preliminarily considered to be pathogenic.
{"title":"De Novo Missense Variant in TP63 Gene: Insights on Clinical and Molecular Investigations","authors":"Jilong Chen, Xufeng Xi, Xiaoman Xu, Yao Lin","doi":"10.1002/jgm.70055","DOIUrl":"10.1002/jgm.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to investigate the phenotypes, mutation types, and loci associated with <i>TP63</i>-related syndrome by focusing on an affected proband.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Employing a proband collection strategy, we identified a family presenting with <i>TP63</i>-related syndrome and performed thorough clinical evaluations on the proband and family members. We subsequently documented the phenotype, mutation type, and locus of the <i>TP63</i> gene, followed by Sanger DNA sequencing analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified a family affected by <i>TP63</i>-related syndrome. The proband, a young adult male, demonstrated congenital anodontia, hypohidrosis, sparse hair, and additional features characteristic of ectodermal dysplasia. Further clinical manifestations included left ear hearing impairment, cleft lip/palate, hypospadias, and syndactyly. Sequencing analysis revealed a missense nucleotide variant (c.184G>C, p.Val62Leu) in exon 2 of the <i>TP63</i> gene. This variant was absent from established SNP databases and was not detected in other family members or unrelated healthy individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The family exhibits significant symptoms consistent with <i>TP63</i> syndrome. The identified missense mutation is preliminarily considered to be pathogenic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12634139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566483","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}
Ahmed S. Doghish, Mai A. Abd-Elmawla, Heba R. Ghaiad, Nora M. Aborehab, Abdullah F. Radwan, Khloud Nassar, Osama A. Mohammed, Hanan Elimam
Non-small cell lung cancer (NSCLC) is considered a major contributor to cancer-related death rates worldwide, chiefly owing to late diagnosis, occurrence of metastasis, and treatment resistance. Growing evidence underscores the impact of long non-coding RNAs (lncRNAs) on NSCLC progression. These lncRNAs have been demonstrated to influence cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and drug resistance, contributing to cancer development and therapeutic failure. Concurrently, natural products and nutraceuticals are gaining attention for their anticancer properties, particularly in modulating signaling pathways involved in tumorigenesis and drug resistance. Compounds like curcumin, resveratrol, and epigallocatechin gallate have been shown to regulate oncogenic lncRNAs, inhibiting metastasis and reversing chemoresistance. Additionally, natural products upregulate tumor-suppressive lncRNAs, restoring cell cycle control and apoptosis. This review provides an in-depth analysis of the etiological significance of lncRNAs in NSCLC, with a particular emphasis on their contribution to tumorigenesis, metastasis, and therapeutic resistance. In addition, it explores the potential of natural products to modulate lncRNA expression, highlighting their efficacy in overcoming drug resistance and enhancing the therapeutic response. By elucidating the dynamic molecular cross-talk between lncRNAs and natural products, this review also aims to identify novel therapeutic strategies and potential biomarkers for the diagnosis and treatment of NSCLC.
{"title":"Natural Products and LncRNAs in Non-Small Cell Lung Cancer: Emerging Therapeutic Approaches","authors":"Ahmed S. Doghish, Mai A. Abd-Elmawla, Heba R. Ghaiad, Nora M. Aborehab, Abdullah F. Radwan, Khloud Nassar, Osama A. Mohammed, Hanan Elimam","doi":"10.1002/jgm.70054","DOIUrl":"10.1002/jgm.70054","url":null,"abstract":"<div>\u0000 \u0000 <p>Non-small cell lung cancer (NSCLC) is considered a major contributor to cancer-related death rates worldwide, chiefly owing to late diagnosis, occurrence of metastasis, and treatment resistance. Growing evidence underscores the impact of long non-coding RNAs (lncRNAs) on NSCLC progression. These lncRNAs have been demonstrated to influence cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and drug resistance, contributing to cancer development and therapeutic failure. Concurrently, natural products and nutraceuticals are gaining attention for their anticancer properties, particularly in modulating signaling pathways involved in tumorigenesis and drug resistance. Compounds like curcumin, resveratrol, and epigallocatechin gallate have been shown to regulate oncogenic lncRNAs, inhibiting metastasis and reversing chemoresistance. Additionally, natural products upregulate tumor-suppressive lncRNAs, restoring cell cycle control and apoptosis. This review provides an in-depth analysis of the etiological significance of lncRNAs in NSCLC, with a particular emphasis on their contribution to tumorigenesis, metastasis, and therapeutic resistance. In addition, it explores the potential of natural products to modulate lncRNA expression, highlighting their efficacy in overcoming drug resistance and enhancing the therapeutic response. By elucidating the dynamic molecular cross-talk between lncRNAs and natural products, this review also aims to identify novel therapeutic strategies and potential biomarkers for the diagnosis and treatment of NSCLC.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558502","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}
Sathan Raj Natarajan, Rajapandiyan Krishnamoorthy, Mohammad A. Alshuniaber, Mansour K. Gatasheh, Ponnulakshmi Rajagopal, Vishnu Priya Veeraraghavan, Chella Perumal Palanisamy, Selvaraj Jayaraman
Background
Colorectal cancer (CRC) is a major cause of cancer-related death and is driven by epigenetic alterations. KDM1A, a key histone demethylase, has a poorly defined role in CRC. This study investigates its molecular mechanisms using bioinformatic and experimental analyses to better understand its impact on tumor progression.
Methods
KDM1A expression was analyzed using TCGA datasets to assess its correlation with CRC progression and patient survival. CRC cell lines were treated with the KDM1A-specific inhibitor GSK2879552, both alone and in combination with 5-Aza and XAV939. Functional assays, including cell proliferation, cell cycle analysis, ROS measurement, glycolysis assessment, and G6PD activity, were performed to evaluate the effects of KDM1A inhibition. Protein and gene expression were examined by Western blotting and RT-PCR analysis.
Results
KDM1A expression was significantly upregulated in advanced CRC and was associated with poor survival. Treatment with GSK2879552 inhibited CRC cell proliferation, induced G1-phase arrest, reduced aerobic glycolysis, and increased ROS levels. Combination with 5-Aza and XAV939 further enhanced the antitumor effects, demonstrating synergistic potential in CRC cells.
Conclusions
KDM1A regulates CRC progression by modulating epithelial-mesenchymal transition (EMT), metabolism, and Wnt signaling. Targeting KDM1A with GSK2879552 represents a promising therapeutic strategy for CRC treatment.
{"title":"KDM1A Facilitates Oncogenic Potential in Colorectal Cancer Progression Through the Activation of AXIN/GSK3β/β-Catenin Signaling Pathways: Evidence From Integrated Transcriptomics and In Vitro Studies","authors":"Sathan Raj Natarajan, Rajapandiyan Krishnamoorthy, Mohammad A. Alshuniaber, Mansour K. Gatasheh, Ponnulakshmi Rajagopal, Vishnu Priya Veeraraghavan, Chella Perumal Palanisamy, Selvaraj Jayaraman","doi":"10.1002/jgm.70053","DOIUrl":"10.1002/jgm.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal cancer (CRC) is a major cause of cancer-related death and is driven by epigenetic alterations. KDM1A, a key histone demethylase, has a poorly defined role in CRC. This study investigates its molecular mechanisms using bioinformatic and experimental analyses to better understand its impact on tumor progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>KDM1A expression was analyzed using TCGA datasets to assess its correlation with CRC progression and patient survival. CRC cell lines were treated with the KDM1A-specific inhibitor GSK2879552, both alone and in combination with 5-Aza and XAV939. Functional assays, including cell proliferation, cell cycle analysis, ROS measurement, glycolysis assessment, and G6PD activity, were performed to evaluate the effects of KDM1A inhibition. Protein and gene expression were examined by Western blotting and RT-PCR analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>KDM1A expression was significantly upregulated in advanced CRC and was associated with poor survival. Treatment with GSK2879552 inhibited CRC cell proliferation, induced G1-phase arrest, reduced aerobic glycolysis, and increased ROS levels. Combination with 5-Aza and XAV939 further enhanced the antitumor effects, demonstrating synergistic potential in CRC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>KDM1A regulates CRC progression by modulating epithelial-mesenchymal transition (EMT), metabolism, and Wnt signaling. Targeting KDM1A with GSK2879552 represents a promising therapeutic strategy for CRC treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552034","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}
Acute pancreatitis (AP) is a severe inflammatory disease. Transient receptor potential (TRP) channels have been reported to participate in various pathophysiological processes. However, the role of TRP channels in the AP remains unclear. Here, we investigated the involvement of TRP channels in AP.
Methods
We identified differentially expressed genes (DEGs) using the public AP datasets GSE3644 and GSE109227 and identified 20 hub genes. We analyzed their correlation with the TRP genes. Four DEGs related to TRP channels were selected, and functional enrichment analyses were conducted. An interaction network involving the transcription factors, microRNAs (miRNAs), and mRNA of the four TRP-associated genes was established. To evaluate the diagnostic effectiveness, receiver operating characteristic (ROC) analysis and machine learning (ML) methods, such as support vector classifiers and random forest, were applied. Furthermore, we analyzed immune cell infiltration and its relationship with the four TRP genes. To confirm these bioinformatics findings, we performed in vitro and in vivo experiments using primary acinar cells and an experimental mouse model of AP.
Results
Four TRP-related genes, namely, MCOLN1, MCOLN3, TRPM7, and TRPV4, were selected for the correlation analysis. Functional analyses showed that these four genes are involved in cellular senescence and the calcium signaling pathway. A TF–miRNA–mRNA interaction network was constructed for the four TRP-associated genes. The areas under the ROC curves (AUC) of MCOLN1, MCOLN3, TRPM7, and TRPV4 were 0.833, 0.700, 1.0, and 1.0, respectively. ML algorithms performed well in predicting AP with AUCs ≥ 0.67. TRPM7, TRPV4, and MCOLN3 are associated with immune cell infiltration of AP tissues. Using experimental AP models, we found that the expression of three TRP-related genes, MCOLN1, TRPM7, and TRPV4, was significantly upregulated in mouse AP tissues. Specifically, TRPM7 knockdown or inhibition by its inhibitor 2-APB significantly reduced pancreatic acinar cell damage, inflammatory mediator expression, and mRNA levels of senescence-associated genes.
Conclusions
Our study suggests that TRP-related genes play crucial roles in AP and may be promising biomarkers for predicting the pathogenesis of AP.
{"title":"Identification of the Role of Transient Receptor Potential Channels in Acute Pancreatitis","authors":"Shuangjun Shen, Xiaowan Wu, Zhiyuan Cheng, Ruiyan Wang, Jing Jiang, Weiliang Jiang","doi":"10.1002/jgm.70057","DOIUrl":"10.1002/jgm.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute pancreatitis (AP) is a severe inflammatory disease. Transient receptor potential (TRP) channels have been reported to participate in various pathophysiological processes. However, the role of TRP channels in the AP remains unclear. Here, we investigated the involvement of TRP channels in AP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified differentially expressed genes (DEGs) using the public AP datasets GSE3644 and GSE109227 and identified 20 hub genes. We analyzed their correlation with the TRP genes. Four DEGs related to TRP channels were selected, and functional enrichment analyses were conducted. An interaction network involving the transcription factors, microRNAs (miRNAs), and mRNA of the four TRP-associated genes was established. To evaluate the diagnostic effectiveness, receiver operating characteristic (ROC) analysis and machine learning (ML) methods, such as support vector classifiers and random forest, were applied. Furthermore, we analyzed immune cell infiltration and its relationship with the four TRP genes. To confirm these bioinformatics findings, we performed in vitro and in vivo experiments using primary acinar cells and an experimental mouse model of AP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four TRP-related genes, namely, <i>MCOLN1</i>, <i>MCOLN3</i>, <i>TRPM7</i>, and <i>TRPV4</i>, were selected for the correlation analysis. Functional analyses showed that these four genes are involved in cellular senescence and the calcium signaling pathway. A TF–miRNA–mRNA interaction network was constructed for the four TRP-associated genes. The areas under the ROC curves (AUC) of <i>MCOLN1</i>, <i>MCOLN3</i>, <i>TRPM7</i>, and <i>TRPV4</i> were 0.833, 0.700, 1.0, and 1.0, respectively. ML algorithms performed well in predicting AP with AUCs ≥ 0.67. <i>TRPM7</i>, <i>TRPV4</i>, and <i>MCOLN3</i> are associated with immune cell infiltration of AP tissues. Using experimental AP models, we found that the expression of three TRP-related genes, <i>MCOLN1</i>, <i>TRPM7</i>, and <i>TRPV4</i>, was significantly upregulated in mouse AP tissues. Specifically, TRPM7 knockdown or inhibition by its inhibitor 2-APB significantly reduced pancreatic acinar cell damage, inflammatory mediator expression, and mRNA levels of senescence-associated genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study suggests that TRP-related genes play crucial roles in AP and may be promising biomarkers for predicting the pathogenesis of AP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535027","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}
Spread through air spaces (STAS), a mode of lung cancer progression, is recognized as a poor prognostic factor, although its pathogenesis remains unclear. This study aimed to identify microRNAs (miRNAs) associated with STAS.
Methods
Differentially expressed miRNAs were identified using miRNA array analysis of primary lung cancer tumor tissues and tissues suspected of STAS obtained from patients who underwent surgery for lung adenocarcinoma. We collected 20 samples (10 from the main tumor tissue; 10 from STAS lesions) from 10 patients.
Results
With two samples exhibiting an RNA integrity number > 7, we performed miRNA analysis of the main tumor tissues and STAS lesions, identifying miRNAs differentially expressed in both cases. In both cases, miR-3136-5p was upregulated, and miR-3934-5p and miR-4793-3p were downregulated. We identified miRNAs with dysregulated expression in STAS tissues compared with those in tumor tissues.
Conclusions
We identified three miRNAs involved in STAS of lung cancer, and these miRNAs may be potential diagnostic and prognostic targets for STAS treatment. As research and development of small RNA-targeted therapeutics targeting cancer, inflammatory diseases, and cardiovascular diseases are progressing, the analysis of miRNA expression levels in STAS of lung cancer may lead to the development of diagnostic markers and potential treatment strategies for lung cancer with STAS.
Trial Registration
Registry: Kagawa University. Registration number: 2021-031. Date of registration: May 28, 2021.
{"title":"MicroRNA Profile Predicts Tumor Spread Through Air Spaces in Resected Lung Adenocarcinomas: A Pilot Study","authors":"Chihiro Yoshida, Kyuichi Kadota, Futoshi Suizu, Emi Ibuki, Ryou Ishikawa, Reiji Haba, Toshiki Yajima","doi":"10.1002/jgm.70051","DOIUrl":"10.1002/jgm.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spread through air spaces (STAS), a mode of lung cancer progression, is recognized as a poor prognostic factor, although its pathogenesis remains unclear. This study aimed to identify microRNAs (miRNAs) associated with STAS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Differentially expressed miRNAs were identified using miRNA array analysis of primary lung cancer tumor tissues and tissues suspected of STAS obtained from patients who underwent surgery for lung adenocarcinoma. We collected 20 samples (10 from the main tumor tissue; 10 from STAS lesions) from 10 patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>With two samples exhibiting an RNA integrity number > 7, we performed miRNA analysis of the main tumor tissues and STAS lesions, identifying miRNAs differentially expressed in both cases. In both cases, miR-3136-5p was upregulated, and miR-3934-5p and miR-4793-3p were downregulated. We identified miRNAs with dysregulated expression in STAS tissues compared with those in tumor tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We identified three miRNAs involved in STAS of lung cancer, and these miRNAs may be potential diagnostic and prognostic targets for STAS treatment. As research and development of small RNA-targeted therapeutics targeting cancer, inflammatory diseases, and cardiovascular diseases are progressing, the analysis of miRNA expression levels in STAS of lung cancer may lead to the development of diagnostic markers and potential treatment strategies for lung cancer with STAS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Registry: Kagawa University. Registration number: 2021-031. Date of registration: May 28, 2021.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535077","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}
Osteoporosis and osteosarcoma share certain molecular pathways, and identifying common hub genes could provide new insights into their pathogenesis. This study aimed to identify and validate hub genes involved in both osteoporosis and osteosarcoma and explore their potential as biomarkers and therapeutic targets.
Methods
We retrieved three publicly available datasets: GSE13850 (osteoporosis), GSE16088, and GSE12865 (osteosarcoma). Differentially expressed genes (DEGs) were identified using the limma package in R, and common DEGs were determined through Venn analysis. The hub genes were identified using the STRING database and Cytoscape software. Reverse transcription quantitative PCR was used to validate gene expression in osteosarcoma cell lines and normal bone tissue cell lines. Functional assays including cell proliferation, colony formation, and wound healing were conducted after CLTA and SMAD3 knockdown via small interfering RNA. Gene set enrichment, promoter methylation analysis, and genetic alteration studies were conducted using publicly available databases.
Results
The hub genes identified, CLTA, MSR1, MTF2, and SMAD3, were highly expressed in osteosarcoma compared to normal controls, and their expression was validated across osteosarcoma tissue samples. Survival analysis showed that high expression of these genes correlated with poor prognosis in osteosarcoma patients. Gene enrichment analysis suggested that these genes play crucial roles in osteosarcoma development through various signaling pathways. CLTA and SMAD3 silencing in MG63 and U2OS cells led to significant reductions in cell proliferation, colony formation, and migration.
Conclusions
This study identified CLTA, MSR1, MTF2, and SMAD3 as potential biomarkers and therapeutic targets for osteoporosis and osteosarcoma. However, further studies are needed before determining clinical implications.
{"title":"Molecular Crosstalk Between Osteoporosis and Osteosarcoma: Identification of Common Diagnostic Markers and Therapeutic Targets","authors":"Yong Zhou, Jianxin Huang","doi":"10.1002/jgm.70056","DOIUrl":"10.1002/jgm.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Osteoporosis and osteosarcoma share certain molecular pathways, and identifying common hub genes could provide new insights into their pathogenesis. This study aimed to identify and validate hub genes involved in both osteoporosis and osteosarcoma and explore their potential as biomarkers and therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrieved three publicly available datasets: GSE13850 (osteoporosis), GSE16088, and GSE12865 (osteosarcoma). Differentially expressed genes (DEGs) were identified using the limma package in R, and common DEGs were determined through Venn analysis. The hub genes were identified using the STRING database and Cytoscape software. Reverse transcription quantitative PCR was used to validate gene expression in osteosarcoma cell lines and normal bone tissue cell lines. Functional assays including cell proliferation, colony formation, and wound healing were conducted after CLTA and SMAD3 knockdown via small interfering RNA. Gene set enrichment, promoter methylation analysis, and genetic alteration studies were conducted using publicly available databases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The hub genes identified, CLTA, MSR1, MTF2, and SMAD3, were highly expressed in osteosarcoma compared to normal controls, and their expression was validated across osteosarcoma tissue samples. Survival analysis showed that high expression of these genes correlated with poor prognosis in osteosarcoma patients. Gene enrichment analysis suggested that these genes play crucial roles in osteosarcoma development through various signaling pathways. CLTA and SMAD3 silencing in MG63 and U2OS cells led to significant reductions in cell proliferation, colony formation, and migration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified CLTA, MSR1, MTF2, and SMAD3 as potential biomarkers and therapeutic targets for osteoporosis and osteosarcoma. However, further studies are needed before determining clinical implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515203","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}
Areej Nazarudeen, V. A. Aswathy, Arun A. Rauf, U. V. Aswathy, V. R. Mahesh Chandran, N. Abhirami, S. Sudhina, Akash Chandran, Janeesh Plakkal Ayyappan
Atherosclerosis is a chronic inflammatory condition that remains a major global cause of cardiovascular morbidity and death. Circular RNAs (circRNAs), emerging as key regulators of biological processes, have been linked to atherosclerosis because of their functions in inflammation, lipid metabolism, and plaque stability. This review explores the biogenesis and cellular functions of circRNAs, highlighting specific circRNAs, such as circANRIL, circHIPK, and circRSF1, which influence atherosclerosis progressions and development. CRISPR-Cas technology, specifically Cas9 and Cas13, has transformed the way atherosclerosis is studied and potentially treated. Targeting PCSK9, LDLR, and APOB to modify lipid metabolism, including lowering LDL cholesterol and repairing mutations in familial hypercholesterolemia, has been made possible using CRISPR-Cas9 in atherosclerosis models. In parallel, CRISPR-Cas13 offers a novel approach for RNA-level intervention by selectively editing circRNAs, providing a dynamic approach to regulate atherosclerosis-related pathways. In order to convert these findings into therapeutic treatments, future research should focus on elucidating the mechanics of circRNA, which in turn determines CRISPR-Cas13, and designing specific delivery systems. This review paper demonstrates the revolutionary promise of circRNA research and CRISPR innovation in the treatment of atherosclerosis and underscores the need for extensive preclinical validation to bridge the gap towards clinical use.
{"title":"Targeting Circular RNAs (circRNAs) in Atherosclerosis Using CRISPR Technology","authors":"Areej Nazarudeen, V. A. Aswathy, Arun A. Rauf, U. V. Aswathy, V. R. Mahesh Chandran, N. Abhirami, S. Sudhina, Akash Chandran, Janeesh Plakkal Ayyappan","doi":"10.1002/jgm.70048","DOIUrl":"10.1002/jgm.70048","url":null,"abstract":"<div>\u0000 \u0000 <p>Atherosclerosis is a chronic inflammatory condition that remains a major global cause of cardiovascular morbidity and death. Circular RNAs (circRNAs), emerging as key regulators of biological processes, have been linked to atherosclerosis because of their functions in inflammation, lipid metabolism, and plaque stability. This review explores the biogenesis and cellular functions of circRNAs, highlighting specific circRNAs, such as circANRIL, circHIPK, and circRSF1, which influence atherosclerosis progressions and development. CRISPR-Cas technology, specifically Cas9 and Cas13, has transformed the way atherosclerosis is studied and potentially treated. Targeting PCSK9, LDLR, and APOB to modify lipid metabolism, including lowering LDL cholesterol and repairing mutations in familial hypercholesterolemia, has been made possible using CRISPR-Cas9 in atherosclerosis models. In parallel, CRISPR-Cas13 offers a novel approach for RNA-level intervention by selectively editing circRNAs, providing a dynamic approach to regulate atherosclerosis-related pathways. In order to convert these findings into therapeutic treatments, future research should focus on elucidating the mechanics of circRNA, which in turn determines CRISPR-Cas13, and designing specific delivery systems. This review paper demonstrates the revolutionary promise of circRNA research and CRISPR innovation in the treatment of atherosclerosis and underscores the need for extensive preclinical validation to bridge the gap towards clinical use.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497481","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}
Fragile X syndrome (FXS) is the most common single gene cause of inherited intellectual disability and autism spectrum disorder (ASD). FMR1, the gene associated with FXS, is located on chromosome X. Accordingly, males with loss-of-function (full) mutations are more severely affected than females. Strategies for therapeutic intervention for this disorder have included behavioral and medication therapy. To date, no management strategies have been shown to be curative. Gene therapy that aims to supply the functional protein product of the gene FMR1 to the brain is an attractive concept for curative treatment. Experiments aimed at activating the mutant FMR1, modifying its abnormal RNA product, or supplying functional FMR1 copies to the CNS have been conducted. The delivery of the FMR1 gene and its product to animal models of FXS have been primarily conducted with intrathecal applications because of the low efficiency of the gene therapy vectors to cross the blood–brain barrier (BBB). This delivery approach is associated with a higher risk of complications and appears to distribute the gene product unevenly across different brain regions. We have explored the efficiency of a recently developed adeno-associated virus (AAV) vector with increased BBB crossing in certain strains of mice to deliver FMR1 with peripheral IV administration. Our experiments demonstrated very high delivery efficiency and also highlighted the risk of oversupplying the brain with FMRP, the protein product of the FMR1 gene. Other AAV vectors with enhanced crossing of the BBB in primates have been developed, providing an attractive option for further experiments involving peripheral administration. Providing the gene product to specific brain cells remains a difficult challenge for future experiments. It may also be important or even necessary to regulate the gene expression to mimic physiological expression patterns since the levels of FMRP change dramatically during development, with maximum levels early in the postnatal period and a decline across early life. In addition, there are 12 identified mouse isoforms of FMRP due to alternative RNA splicing, and an even higher number of isoforms is found in humans. It may thus be a challenge to determine what FMR1 isoform or set of isoforms would have the optimum efficiency in correcting the phenotype. Despite these challenges, the recent developments establish the basis for future research to develop efficient and minimally invasive gene therapy protocols for FXS.
{"title":"Gene Therapy for Fragile X Syndrome, Challenges, and Promises","authors":"Milen Velinov","doi":"10.1002/jgm.70049","DOIUrl":"10.1002/jgm.70049","url":null,"abstract":"<p>Fragile X syndrome (FXS) is the most common single gene cause of inherited intellectual disability and autism spectrum disorder (ASD). <i>FMR1</i>, the gene associated with FXS, is located on chromosome X. Accordingly, males with loss-of-function (full) mutations are more severely affected than females. Strategies for therapeutic intervention for this disorder have included behavioral and medication therapy. To date, no management strategies have been shown to be curative. Gene therapy that aims to supply the functional protein product of the gene <i>FMR1</i> to the brain is an attractive concept for curative treatment. Experiments aimed at activating the mutant <i>FMR1</i>, modifying its abnormal RNA product, or supplying functional <i>FMR1</i> copies to the CNS have been conducted. The delivery of the FMR1 gene and its product to animal models of FXS have been primarily conducted with intrathecal applications because of the low efficiency of the gene therapy vectors to cross the blood–brain barrier (BBB). This delivery approach is associated with a higher risk of complications and appears to distribute the gene product unevenly across different brain regions. We have explored the efficiency of a recently developed adeno-associated virus (AAV) vector with increased BBB crossing in certain strains of mice to deliver <i>FMR1</i> with peripheral IV administration. Our experiments demonstrated very high delivery efficiency and also highlighted the risk of oversupplying the brain with FMRP, the protein product of the <i>FMR1</i> gene. Other AAV vectors with enhanced crossing of the BBB in primates have been developed, providing an attractive option for further experiments involving peripheral administration. Providing the gene product to specific brain cells remains a difficult challenge for future experiments. It may also be important or even necessary to regulate the gene expression to mimic physiological expression patterns since the levels of FMRP change dramatically during development, with maximum levels early in the postnatal period and a decline across early life. In addition, there are 12 identified mouse isoforms of FMRP due to alternative RNA splicing, and an even higher number of isoforms is found in humans. It may thus be a challenge to determine what <i>FMR1</i> isoform or set of isoforms would have the optimum efficiency in correcting the phenotype. Despite these challenges, the recent developments establish the basis for future research to develop efficient and minimally invasive gene therapy protocols for FXS.</p>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12597487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483972","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}
Diabetes mellitus (DM) is a chronic metabolic disease, and some diabetic patients develop diabetic foot ulcers (DFU), which are one of the most prevalent and serious complications among diabetic patients. These ulcers can lead to neuropathy, vasculopathy and severe infections. LncRNAs, a class of long-stranded noncoding RNAs that regulate gene expression, have been shown to play a critical regulatory role in diabetic foot ulcer wound healing. These molecules have been demonstrated to modulate numerous facets of the inflammatory response, cell proliferation and angiogenesis, which collectively influence the outcome of wound healing. A substantial body of research has emerged in recent years, highlighting the critical role of these noncoding transcripts in DFU. This paper reviews recent research advances on the regulatory functions and potential mechanisms of noncoding transcripts in the healing of diabetic foot ulcers, based on a literature search of databases such as PubMed and Web of Science over the past decade.
糖尿病（DM）是一种慢性代谢性疾病，部分糖尿病患者发生糖尿病足溃疡（DFU），是糖尿病患者最常见、最严重的并发症之一。这些溃疡可导致神经病变、血管病变和严重感染。LncRNAs是一类调节基因表达的长链非编码rna，已被证明在糖尿病足溃疡创面愈合中发挥关键的调节作用。这些分子已被证明可以调节炎症反应、细胞增殖和血管生成的许多方面，这些方面共同影响伤口愈合的结果。近年来出现了大量的研究，强调了这些非编码转录本在DFU中的关键作用。本文通过对PubMed、Web of Science等数据库近十年的文献检索，综述了近年来非编码转录本在糖尿病足溃疡愈合中的调控作用及其潜在机制的研究进展。
{"title":"Mechanisms of lncRNA in Diabetic Foot Ulcer Wound Healing","authors":"Yiming Chen, Mengting Wang, Xiaoliang Cao, Shengfeng Gao, Yasu Jiang, Zhenhua Gong","doi":"10.1002/jgm.70050","DOIUrl":"10.1002/jgm.70050","url":null,"abstract":"<p>Diabetes mellitus (DM) is a chronic metabolic disease, and some diabetic patients develop diabetic foot ulcers (DFU), which are one of the most prevalent and serious complications among diabetic patients. These ulcers can lead to neuropathy, vasculopathy and severe infections. LncRNAs, a class of long-stranded noncoding RNAs that regulate gene expression, have been shown to play a critical regulatory role in diabetic foot ulcer wound healing. These molecules have been demonstrated to modulate numerous facets of the inflammatory response, cell proliferation and angiogenesis, which collectively influence the outcome of wound healing. A substantial body of research has emerged in recent years, highlighting the critical role of these noncoding transcripts in DFU. This paper reviews recent research advances on the regulatory functions and potential mechanisms of noncoding transcripts in the healing of diabetic foot ulcers, based on a literature search of databases such as PubMed and Web of Science over the past decade.</p>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12597133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483988","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}
Hatem M. Hadeed, Maarib N. Rasheed, Ahmed AbdulJabbar Suleiman
Introduction
Breast cancer is a malignant tumor that originates in breast tissue and the most common cause of malignant tumors-related death in women worldwide. Long noncoding RNA (LncRNA) is a transcribed RNA with more than 200 nucleotides in length but has no notable potential for protein coding. Hypoxia is a common occurrence in tumor microenvironments due to an imbalance in oxygen supply and consumption by rapidly growing tumors. The aim of study is to analyze the gene expression of different types of lncRNAs (lnc.4.2, lnc.4.3) as a molecular tumor marker in relation with hypoxia-inducible factor 1alpha (HIF-1α) gene and main clinic pathological characters for patients and healthy control group.
Methods
The study included 100 newly diagnosed cases of bc divided into four groups: (n = 25) low grade before treatment (LBT), (n = 25) low grade after treatment (LAT), (n = 25) high grade before treatment (HBT), and (n = 25) high grade after treatment (HAT). In addition, (n = 25) as a control group.
Results
The results of this study showed that lncRNA 4.2 and lncRNA 4.3 exhibited strong discriminatory ability specifically in the LBT versus control and HAT versus control comparisons, with AUC values exceeding 0.70. This indicates that these lncRNAs may be particularly useful for distinguishing LBT and HAT samples indicate potential role in treatment response or the pretreatment state. HIF1A also exhibited moderate diagnostic potential in the HBT versus control and HAT versus control comparisons, with AUC values greater than 0.60. Its performance was notably better in the HBT group, where it achieved an AUC of 0.774, indicating good discriminatory ability in this specific context. This suggests that HIF1A may be a useful diagnostic marker for conditions associated with HBT samples, potentially reflecting its role in cellular stress response.
{"title":"Long Noncoding RNAs (LncRNA-4.2, LncRNA-4.3) and Their Correlation With Hypoxia-Related Biomarkers in Breast Cancer","authors":"Hatem M. Hadeed, Maarib N. Rasheed, Ahmed AbdulJabbar Suleiman","doi":"10.1002/jgm.70047","DOIUrl":"https://doi.org/10.1002/jgm.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Breast cancer is a malignant tumor that originates in breast tissue and the most common cause of malignant tumors-related death in women worldwide. Long noncoding RNA (LncRNA) is a transcribed RNA with more than 200 nucleotides in length but has no notable potential for protein coding. Hypoxia is a common occurrence in tumor microenvironments due to an imbalance in oxygen supply and consumption by rapidly growing tumors. The aim of study is to analyze the gene expression of different types of lncRNAs (lnc.4.2, lnc.4.3) as a molecular tumor marker in relation with hypoxia-inducible factor 1alpha (HIF-1α) gene and main clinic pathological characters for patients and healthy control group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 100 newly diagnosed cases of <span>bc</span> divided into four groups: (<i>n</i> = 25) low grade before treatment (LBT), (<i>n</i> = 25) low grade after treatment (LAT), (<i>n</i> = 25) high grade before treatment (HBT), and (<i>n</i> = 25) high grade after treatment (HAT). In addition, (<i>n</i> = 25) as a control group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results of this study showed that lncRNA 4.2 and lncRNA 4.3 exhibited strong discriminatory ability specifically in the LBT versus control and HAT versus control comparisons, with AUC values exceeding 0.70. This indicates that these lncRNAs may be particularly useful for distinguishing LBT and HAT samples indicate potential role in treatment response or the pretreatment state. HIF1A also exhibited moderate diagnostic potential in the HBT versus control and HAT versus control comparisons, with AUC values greater than 0.60. Its performance was notably better in the HBT group, where it achieved an AUC of 0.774, indicating good discriminatory ability in this specific context. This suggests that HIF1A may be a useful diagnostic marker for conditions associated with HBT samples, potentially reflecting its role in cellular stress response.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443020","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}
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