Gene最新文献

{"title":"Identification of genetic variants in MTHFD1 associated with risk of hypertension.","authors":"Yi Zhong, Xiaobo Li, Zhenbo Wang, Yixiu Yang, Pingdong Xie, Yunjun Zhang, Xiaoli Zhou, Qi Lin, Chanyi He, Shuli Du, Tianbo Jin, Quanni Li, Yipeng Ding","doi":"10.1016/j.gene.2025.149310","DOIUrl":"https://doi.org/10.1016/j.gene.2025.149310","url":null,"abstract":"<p><strong>Background: </strong>MTHFD1, involved in folate metabolism, has been associated with various health outcomes, including cardiovascular diseases. This study aimed to investigate the association between four single nucleotide polymorphisms (SNPs) in MTHFD1 and the risk of hypertension.</p><p><strong>Methods: </strong>We conducted a case-control study involving 838 hypertensive patients and 438 controls. Genotyping for four MTHFD1 SNPs was performed using the Agena MassARRAY platform. The association between these SNPs and hypertension risk was evaluated using logistic regression, adjusting for age and sex. Stratified analysis was conducted and visualized using Sangerbox software. The Multifactor Dimensionality Reduction (MDR) method was applied to assess SNP-SNP interactions.</p><p><strong>Results: </strong>Our results analysis revealed a significant correlation between the rs1950902 SNP and an increased risk of hypertension in overall, males and individuals aged 69 years or younger; rs8016556 was associated with a decreased risk of hypertension, particularly in females; and rs11849530 was also linked to a reduced risk of hypertension, especially in older individuals. SNP-SNP interaction analysis revealed significant interactions between the four SNPs, suggesting a joint effect on hypertension risk.</p><p><strong>Conclusions: </strong>Our findings suggest that certain MTHFD1 polymorphisms (rs1950902, rs8016556, and rs11849530) are associated with the risk of hypertension, and these associations may be influenced by gender and age.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149310"},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in gene activation and regulation.","authors":"Sukesh R Bhaumik","doi":"10.1016/j.gene.2025.149306","DOIUrl":"10.1016/j.gene.2025.149306","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149306"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between genotypes of ABCB1 and ABCG2 and the risk of atrial fibrillation","authors":"Tzu-Yu Pan ,&nbsp;Tzu-Yen Lin ,&nbsp;Wei-Chung Tsai ,&nbsp;Ming-Tsang Wu","doi":"10.1016/j.gene.2025.149307","DOIUrl":"10.1016/j.gene.2025.149307","url":null,"abstract":"<div><h3>Aims</h3><div>Atrial fibrillation (AF) is a prevalent clinical condition worldwide, with a high global incidence that significantly impacts disease burden and mortality rates. Single nucleotide polymorphisms in <em>ABCB1</em> and <em>ABCG2</em> are common, but the clinical outcomes are poorly understood. This study examines the association between the genetic variations of <em>ABCB1</em> and <em>ABCG2</em> and the risk of AF in a Taiwanese population.</div></div><div><h3>Methods and results</h3><div>This case-control study recruited 216 AF patients from two hospitals in Taiwan between 2021 and 2023. Control groups were matched by age (± one year), gender, and AF-related variables from the Taiwan Biobank. Logistic regression analyzed the association between three genetic variants and AF risk. A significant association was noted between <em>ABCG2 rs2231142</em> and AF risk. Those with <em>ABCG2 rs2231142 G/T</em> and <em>T/T</em> genotypes had a 1.91-fold (95 % CI = 1.04–3.53) increased risk of AF compared to those with the G/G genotype. This association was particularly pronounced in males in those carrying <em>ABCG2 rs2231143 T/T</em> genotype having a 4.47-fold (95 % CI = 1.02–19.67) increased risk after adjusting for covariates. There were no overall significant associations between AF risk and the polymorphisms of <em>ABCB1 rs4148738</em> and <em>rs1128503.</em></div></div><div><h3>Conclusion</h3><div>A robust risk association between the <em>ABCG2 rs2231142 T allele</em> and AF in Asian populations, particularly in male adults, suggests that genetic testing for this polymorphism could be integrated into risk assessment models for AF.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"945 ","pages":"Article 149307"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs as behind-the-scenes molecules in breast cancer metastasis and their therapeutic role through novel microRNA-based delivery strategies","authors":"Mohamed J. Saadh ,&nbsp;Ashok Kumar Bishoyi ,&nbsp;Suhas Ballal ,&nbsp;Abhayveer Singh ,&nbsp;Radhwan Abdul Kareem ,&nbsp;Anita Devi ,&nbsp;Girish Chandra Sharma ,&nbsp;K.Satyam Naidu ,&nbsp;Fadhil Faez Sead","doi":"10.1016/j.gene.2025.149272","DOIUrl":"10.1016/j.gene.2025.149272","url":null,"abstract":"<div><div>Breast cancer is the primary cause of cancer-related death and the most frequent malignancy among women in Western countries. Although there have been advancements in combination treatments and targeted therapies for the metastatic diseases management, metastatic breast cancer is still the second most common cause of cancer-related deaths among U.S. women. The routes of metastasis encompass invasion, intravasation, circulation, extravasation, infiltration into a remote location to establish a metastatic niche, and the formation of micro-metastases in a new environment. Each of these processes is regulated by changes in gene expression. MicroRNAs (miRNAs) are widely expressed by a variety of organisms and have a key role in cell activities including suppressing or promoting cancer through regulating various pathways. Target gene expression is post-transcriptionally regulated by miRNAs, which contribute to the development, spread, and metastasis of breast cancer. In this study, we comprehensively discussed the role of miRNAs as predictors of breast cancer metastasis, their correlation with the spread of the disease to certain organs, and their potential application as targets for breast cancer treatment. We also provided molecular mechanisms of miRNAs in the progression of breast cancer, as well as current challenges in miRNA-based therapeutic approaches. Furthermore, as one of the primary issues with the treatment of solid malignancies is the efficient delivery of miRNAs, we examined a number of cutting-edge carriers for miRNA-based therapies and CRISPR/Cas9 as a targeted therapy for breast cancer.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"944 ","pages":"Article 149272"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of mitochondrial solute carrier family 25 (SLC25) identifies member 19 (SLC25A19) as a regulatory factor in hepatocellular carcinoma","authors":"Xueke Gao ,&nbsp;Yangtao Xu ,&nbsp;Xinyao Hu,&nbsp;Jiayu Chen,&nbsp;Daoming Zhang,&nbsp;Ximing Xu","doi":"10.1016/j.gene.2025.149299","DOIUrl":"10.1016/j.gene.2025.149299","url":null,"abstract":"<div><h3>Background</h3><div>The mitochondrial solute carrier family 25 (SLC25) is known to play a pivotal role in oncogenesis, yet its specific involvement in hepatocellular carcinoma (HCC) remains poorly elucidated.</div></div><div><h3>Methods</h3><div>In this study, we performed a clustering analysis of HCC patients in the Cancer Genome Atlas database based on the expression levels of SLC25 members, and conducted clinical feature analysis for each patient within the clusters. Subsequently, we developed a prognostic model using a Lasso regression approach with SLC25A19, SLC25A49, and SLC25A51 as features, and generated a risk score for each HCC patient. We then identified SLC25A19 as a potential prognostic marker for HCC through single-cell analysis, and validated this finding using <em>in vitro</em> and <em>in vivo</em> experiments.</div></div><div><h3>Results</h3><div>Our results revealed significant differences in the expression of most SLC25 family members in HCC patients, enabling the stratification of patients into three clusters, with those in cluster 1 exhibiting the most favorable prognosis and showing a correlation with enhanced immune infiltration. The risk scores derived from the features SLC25A19, SLC25A49, and SLC25A51 effectively predicted the prognosis of HCC patients, with area under the curve (AUC) values exceeding 0.7 in the test group. Single-cell analysis further demonstrated h eightened expression of SLC25A19 in the immune microenvironment of HCC, and <em>in vitro</em> experiments indicated that SLC25A19 may regulate the proliferation, migration, invasion, cycle, and apoptosis of liver cancer cells through the Wnt pathway. In the HepG2 animal model, overexpression of SLC25A19 significantly promotes tumor growth, while knockdown inhibits tumor growth. Analysis of patient tumor tissues shows that SLC25A19 is highly expressed in liver cancer tissues and is associated with CD8⁺ T cell infiltration.</div></div><div><h3>Conclusions</h3><div>In conclusion, our comprehensive analysis of the role of SLC25 in HCC unveiled SLC25A19 as a potential regulatory factor in HCC.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"944 ","pages":"Article 149299"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancer RNA from STAT3 locus affects temozolomide chemoresistance of glioblastoma cells","authors":"Ekaterina Mikhailovna Stasevich ,&nbsp;Anastasiia Vladimirovna Simonova ,&nbsp;Anastasiya Valeryevna Poteryakhina ,&nbsp;Elvina Andreevna Bogomolova ,&nbsp;Aksinya Nikolaevna Uvarova ,&nbsp;Elina Alekseevna Zheremyan ,&nbsp;Kirill Viktorovich Korneev ,&nbsp;Anton Markovich Schwartz ,&nbsp;Dmitry Vladimirovich Kuprash ,&nbsp;Denis Eriksonovich Demin","doi":"10.1016/j.gene.2025.149297","DOIUrl":"10.1016/j.gene.2025.149297","url":null,"abstract":"<div><div>Less than ten percent of glioblastoma tumors are sensitive to temozolomide, the primary drug for treating this type of cancer. STAT3 is a well-known regulator of glioblastoma resistance to temozolomide, suppression of its activity sensitizes cells to the treatment. However, systemic suppression of STAT3 may lead to immune dysregulation, possibly interfering with the antitumor effect. Non-coding RNAs expressed from enhancers (enhancer RNA or eRNA) can guide the direction of various cellular processes by controlling the expression of key genes. In this work, we found eRNA from the STAT3 locus (TMZR1-eRNA) that controls the sensitivity of glioblastoma cells to temozolomide. Knockdown of TMZR1-eRNA decreased STAT3 mRNA and protein expression, resulting in a profound reduction in the abundance of temozolomide-treated cells. Using the reporter assay, we showed that eRNA suppression reduced the activity of STAT3 promoter. Patient glioblastoma cells with higher eRNA expression also showed enhanced sensitivity to temozolomide upon eRNA knockdown. Expression of the eRNA in healthy brain tissue and PBMC was observed at markedly lower levels. Taken together, our results suggest TMZR1-eRNA suppression as a more targeted approach to STAT3 inhibition, potentially with minimal side effects.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"944 ","pages":"Article 149297"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes-mediated CRISPR/Cas delivery: A cutting-edge frontier in cancer gene therapy","authors":"Bhavanisha Rithiga S ,&nbsp;Rajib Dhar ,&nbsp;Arikketh Devi","doi":"10.1016/j.gene.2025.149296","DOIUrl":"10.1016/j.gene.2025.149296","url":null,"abstract":"<div><div>Cancer is considered the second most common disease globally. In the past few decades, many approaches have been proposed for cancer treatment. One among those is targeted therapy using CRISPR/Cas system which plays a significant role in translational research through gene editing. However, due to its inability to cope with specific targeting, off-target effects, and limited tumor penetration, it is very challenging to use this approach in cancer studies. To increase its efficacy, CRISPR components are engineered into the extracellular vesicles (EVs), especially exosomes (a subpopulation of EVs). Exosomes have a significant role in cellular communication. Exosomes-based CRISPR/Cas system transport for gene editing enhances specificity, reduces off-target effects, and improves the therapeutic potential. This review highlights the role of exosomes and the CRISPR/Cas system in cancer research, exosomes-based CRISPR delivery for cancer treatment, and its future orientation.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"944 ","pages":"Article 149296"},"PeriodicalIF":2.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of genetic polymorphisms in KCNN2 in cardiovascular complications in patients with renal failure","authors":"Azza A. Gomaa ,&nbsp;Amany M. Zeid ,&nbsp;Ibrahim M. Nagy","doi":"10.1016/j.gene.2025.149269","DOIUrl":"10.1016/j.gene.2025.149269","url":null,"abstract":"<div><div>Patients with end-stage renal disease (ESRD) are at a higher risk of cardiovascular (CV) complications and mortality compared to the general population. This study aimed to investigate the genetic polymorphisms of <em>KCNN2</em>, a key gene encoding a subtype of small-conductance calcium-activated potassium (SK) channels, which regulate an important SK current pathway potentially involved in the development of CV complications, particularly arrhythmias, in ESRD patients. A total of 169 ESRD patients were enrolled in this study. The patients were divided into two groups based on the presence of CV complications: Group I, consisting of 84 patients without CV complications, and Group II, comprising 85 patients with CV complications. Twelve tagging single nucleotide polymorphisms (tSNPs) in <em>KCNN2</em> were examined. Polymerase chain reaction (PCR) was performed, and genotyping was correlated with CV complications in each group. The TC and CC genotypes of rs10076582, and the GT and TT genotypes of rs11738819 in the <em>KCNN2</em> gene, were associated with an increased risk of CV complications in ESRD patients. After adjusting for potential risk factors, these associations remained significant. Additionally, <em>KCNN2</em> haplotypes with the allele combinations GGCCCTCCGAG and AGTCCTCCGGT were significantly associated with a higher risk of CV complications in ESRD patients. In conclusion, our findings report that specific genetic polymorphisms in the <em>KCNN2</em> gene, particularly the rs10076582 and rs11738819 variants, as well as GGCCCTCCGAG and AGTCCTCCGGT haplotypes, are significantly associated with an increased risk of cardiovascular complications in ESRD patients. These genetic markers may serve as potential biomarkers for identifying individuals at high risk of cardiovascular complications in this vulnerable population.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"944 ","pages":"Article 149269"},"PeriodicalIF":2.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of fibrinogen-like 2 (FGL2) proteins in implantation: Potential implications and mechanism.","authors":"Yueying Wang, Mei Wang, Jiawei Kang, Yuanzhen Zhang","doi":"10.1016/j.gene.2025.149284","DOIUrl":"https://doi.org/10.1016/j.gene.2025.149284","url":null,"abstract":"<p><p>Fibrinogen-like (Fgl2) protein belongs to fibrinogen super family, which catalyzes the conversion of prothrombin to thrombin and is involved in the coagulation process. There are two different forms of functional Fgl2 protein: membrane associated Fgl2 (mFgl2) and soluble Fgl2 (sFgl2). mFgl2, as a type II transmembrane protein with property with prothrombinase activity from its N-terminal fragment, was extensively secreted or expressed by inflammatory macrophages, dendritic cells, Th1 cells and endothelial cells. While sFgl2 was mainly produced by regulatory T cells (Tregs) and then secreted into the vasculature, which contributes to autoimmune disease by regulating maturation of dendritic cells (DCs), polarization of macrophage, inhibiting T cell proliferation and differentiation and inducing apoptosis of B cells. In particular, emerging evidence has shown that Fgl2 is implicated in female reproductive system that contributes to embryo development, ovarian granulosa cells differentiation and implantation failure. This article summarizes the role and potential mechanisms of Fgl2 in reproduction and identifies research gaps and identifies research gaps along with the future directions.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149284"},"PeriodicalIF":2.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aldose reductase has a function in salt tolerance of wheat","authors":"Shasha Yang ,&nbsp;Zhishun Yu ,&nbsp;Tingting Yuan ,&nbsp;Mutong Li ,&nbsp;Cancan Zhang ,&nbsp;Qingqin Zhang ,&nbsp;Suqin Zhang ,&nbsp;Guangdong Geng","doi":"10.1016/j.gene.2025.149295","DOIUrl":"10.1016/j.gene.2025.149295","url":null,"abstract":"<div><div>Aldose reductase (ALR) is closely related to the plant’s response to abiotic stresses. Previous transcriptome data from the salt-tolerant <em>Tritipyrum</em> Y1805 indicated that an ALR-related gene was highly upregulated under salt stress. The gene, <em>TtALR1,</em> was successfully cloned from Y1805, with a coding sequence length of 960 bp. Bioinformatics analysis revealed that TtALR1 is hydrophilic and belongs to the AKR4C aldoketone reductase family. A phylogenetic tree grouped TtALR1 with ALRs of wheat and <em>Thinopyrum elongatum</em>. The <em>TtALR1</em> gene was transformed into common wheat 1718 using the coleoptile method. <em>TtALR1</em> expression in roots was highly sensitive to salt stress according to quantitative real-time PCR analysis. At the seedling stage, the degree of leaf wilting and yellowing in the <em>TtALR</em>-overexpression line was less than in wild-type (WT) plants under salt stress. Under salt stress and recovery conditions, root length, plant fresh weight, plant dry weight, and water content of the <em>TtALR</em>-overexpression line were significantly greater than those of WT plants. The <em>TtALR</em>-overexpression line had higher ALR, superoxide dismutase, catalase, and peroxidas activities, and sorbitol, proline, K⁺, and chlorophyll contents, but lower methylglyoxal, malondialdehyde, and Na⁺ contents, as well as lower Na⁺/K⁺ ratio than WT plants under salt stress and recovery conditions. TtALR1 contributes to osmotic regulation, detoxification, and chlorophyll stabilization, thereby enhancing wheat salt tolerance.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"944 ","pages":"Article 149295"},"PeriodicalIF":2.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}