Gene Reports最新文献

{"title":"Manool modulates Keap1/Nrf2/ARE pathway to protect against CCl₄-induced hepatotoxicity in mice","authors":"Hafiza Adeena Saleem Khan ,&nbsp;Imtiaz Mustafa ,&nbsp;Nimra Aziz ,&nbsp;Khalil Ahmad ,&nbsp;Syed Ali Raza Shah ,&nbsp;Jaweria Nisar ,&nbsp;Mirza Muhammad Suleman","doi":"10.1016/j.genrep.2025.102341","DOIUrl":"10.1016/j.genrep.2025.102341","url":null,"abstract":"<div><h3>Background</h3><div>Liver diseases are a major health concern, with oxidative stress being a key contributor to hepatocellular injury. Manool, a diterpene from Salvia species, has reported antioxidant activity, but its hepatoprotective role remains underexplored.</div></div><div><h3>Objective</h3><div>To evaluate the protective effects of Manool against CCl4-induced hepatotoxicity in mice, focusing on the Keap1/Nrf2/ARE pathway.</div></div><div><h3>Methods</h3><div>Forty albino mice (n = 10 per group) were divided into negative control (NC; healthy mice), positive control (PC; CCl4 induced mice without treatment), standard control (SC; CCl4 induced mice treated with silymarin at dose 100 mg/kg body weight), and two treatment groups (Mn-1 and Mn-2; CCl4 induced mice treated with manool at dose of 1 and 2 mg/kg body weight respectively). Treatments were administered for 21 days. Serum liver function markers, oxidative stress indices, apoptotic proteins (Bcl-2, Bax, Caspase-3, Caspase-9), inflammatory mediators (NF-κB, TNF-α, IL-1β, IL-6, COX-2), and gene expression (Keap1, Nrf2, HO-1, NQO1) were assessed. Histopathological examination was performed to confirm liver protection.</div></div><div><h3>Results</h3><div>Manool restored ALT, AST, and protein profiles in a dose-dependent manner. It increased TAC and GST, while reducing TOS. Gene expression analysis showed downregulation of Keap1 and upregulation of Nrf2, HO-1, and NQO1. Manool also reduced pro-apoptotic (Bax, Caspase-3, Caspase-9) and inflammatory markers (NF-κB, TNF-α, IL-1β, IL-6, COX-2), while enhancing anti-apoptotic Bcl-2. Histological analysis confirmed attenuation of CCl₄-induced hepatic damage.</div></div><div><h3>Conclusion</h3><div>Manool exerts hepatoprotective effects by modulating oxidative stress, apoptosis, inflammation, and the Keap1/Nrf2/ARE pathway. These findings support its potential as a natural candidate for managing oxidative liver injury, though further mechanistic and translational studies are warranted.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102341"},"PeriodicalIF":0.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The oncogenic role of TRIP13 in clear cell renal cell carcinoma and the synergistic inhibitory effect of combined DCZ0415 and TI17 therapy","authors":"Sen Wang ,&nbsp;Boyu Zhang ,&nbsp;Mengwei Song ,&nbsp;Ying Zhou,&nbsp;Kadirya Asan,&nbsp;Zihao Yang,&nbsp;Jian Wang,&nbsp;Haiyan Lin,&nbsp;Xiaoxue Song,&nbsp;Xudong Yu,&nbsp;Jing Ji","doi":"10.1016/j.genrep.2025.102336","DOIUrl":"10.1016/j.genrep.2025.102336","url":null,"abstract":"<div><div>This study integrated transcriptomic analysis with multidimensional bioinformatics approaches to systematically elucidate the regulatory roles of AAA+ ATPase family members in clear cell renal cell carcinoma (ccRCC). Through differential expression analysis of TCGA and GEO databases and construction of weighted gene co-expression networks (WGCNA), the key gene TRIP13 was identified. Experimental validation revealed that TRIP13 is significantly upregulated in ccRCC tissues and closely associated with poor patient prognosis, with high expression correlating with markedly reduced overall survival and progression-free survival. Molecular mechanism studies demonstrated that TRIP13 promotes tumor proliferation and migration by activating cell cycle-related pathways (e.g., G2/M checkpoint, E2F targets, normalized enrichment score &gt; 3.0, <em>p</em> &lt; 0.01). Single-cell RNA sequencing further revealed its specific enrichment during the S/G2M phase and regulation of proliferation marker genes such as PCNA. Inhibitor interaction analysis confirmed that DCZ0415 and TI17 synergistically suppress TRIP13 function by targeting critical residues like SER-187. Additionally, TRIP13 expression was positively correlated with the infiltration of effector memory T cells in the tumor microenvironment, suggesting its potential role in immunoregulation. This study identifies TRIP13 as a novel therapeutic target and prognostic biomarker for ccRCC, offering insights into targeted therapy and personalized treatment strategies.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102336"},"PeriodicalIF":0.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a computational whole model of Lacticaseibacillus casei ATCC 393","authors":"Kanganwiro Mugwanda ,&nbsp;Mutsa Takundwa ,&nbsp;Leon M.T. Dicks ,&nbsp;Deepak B. Thimiri Govinda Raj","doi":"10.1016/j.genrep.2025.102335","DOIUrl":"10.1016/j.genrep.2025.102335","url":null,"abstract":"<div><div>Genome-scale metabolic models (GEMs) are important tools for predicting the metabolic behaviour of microorganisms, including probiotics, under diverse environmental conditions and assessing the impact of genome modifications. In this study, a draft genome-scale metabolic model for <em>Lacticaseibacillus casei</em> ATCC 393 was constructed using the ModelSEED pipeline. The draft model was validated through simulations in OptFlux 3. The resulting ilcaseidsm20011 model includes 555 genes, 73 metabolic pathways, 950 reactions, and 1095 compounds. This model provides a foundational framework for understanding <em>L. casei</em> ATCC 393 metabolism, serving as a valuable resource for further studies on probiotic functionality and rational metabolic engineering.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102335"},"PeriodicalIF":0.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Survey of long non-coding RNA HOTTIP expression level in endometriosis","authors":"Parisa Vesal ,&nbsp;Amirhossein Rezvani Rezvandeh ,&nbsp;Namdar Razmavar ,&nbsp;Zivar Salehi ,&nbsp;Farhad Mashayekhi ,&nbsp;Kiana Sojoudi ,&nbsp;Ziba Zahiri ,&nbsp;Zakieh Siahpoosh","doi":"10.1016/j.genrep.2025.102338","DOIUrl":"10.1016/j.genrep.2025.102338","url":null,"abstract":"<div><h3>Background</h3><div>Recent researches have highlighted the promising potential of long non-coding RNA (lncRNAs) as an important regulator in endometriosis. Accumulating shreds of evidence has shown an important role of HOTTIP (HOXA transcript at the distal tip) in cell proliferation, differentiation, and migration. The function of HOTTIP in relation to endometriosis is still not well understood.</div></div><div><h3>Materials and methods</h3><div>The goal of this research was to examine the expression profile of HOTTIP and HOXA genes in 70 matched eutopic endometrium (EU) and ectopic endometrium (EC) samples from women with endometriosis, with 85 normal endometrium control samples (C) from healthy women. Quantitative real-time PCR (qRT-PCR) assay was performed to measure the level of gene expression. Cell viability was assessed using the CCK-8 assay. Two endometriotic cell lines were transfected with siRNA against HOTTIP (si-HOTTIP) and then used to monitor the effect of HOTTIP on the expression of HOXA13. Bioinformatic tools and the Cytoscape platform were utilized to perform network analysis and gene enrichment analysis.</div></div><div><h3>Results</h3><div>Results indicated that the expression of HOXA13 and HOTTIP was elevated in EC and EU samples in comparison to the C group (<em>p</em> &lt; 0.05). However, HOXA9, HOXA10, and HOXA11 showed decreased expression in EC samples compared to their levels in the C and EU samples. The expression levels of HOTTIP RNA showed a positive correlation with HOXA13 in patients with endometriosis. qRT-PCR data exhibited that si-HOTTIP triggered the reduction of both HOTTIP and HOXA13 expression levels and cell viability, and bioinformatics analysis in the Cytoscape platform helped us to make our laboratory results more reliable. In conclusion, the dysregulation of <em>HOXA</em> genes by HOTTIP lncRNA, characterized by the upregulation of <em>HOXA13</em> and the downregulation of <em>HOXA9</em>, <em>HOXA10</em> and <em>HOXA11</em>, suggests its significant role in the development of endometriosis and its potential as a therapeutic target.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102338"},"PeriodicalIF":0.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From fibrosis to malignancy: Insights into the genetic landscape linking idiopathic pulmonary fibrosis and lung cancer","authors":"Sanjukta Dasgupta","doi":"10.1016/j.genrep.2025.102333","DOIUrl":"10.1016/j.genrep.2025.102333","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) markedly increases the risk of developing lung cancer, particularly non-small cell lung cancer (NSCLC); however, the molecular mechanisms underlying this progression remain poorly understood. This review indicates current findings on shared genetic alterations and mechanistic pathways that link chronic fibrotic remodeling with oncogenesis. By systematically analyzing recent transcriptomic and in silico studies, key molecular drivers were identified across five functional domains: extracellular matrix remodeling (e.g., <em>MMP1</em>, <em>SPP1</em>), chronic inflammation (e.g., <em>C1q</em>, <em>CCL13</em>), oxidative stress and genomic instability (e.g., <em>TP53</em>, <em>SETD2</em>), surfactant dysfunction (e.g., SFTPC, SFTPB), and dysregulated growth factor signaling (e.g., <em>EGFR</em>, <em>PIK3CA</em>). Emerging candidates such as <em>PLA2G7</em> and <em>SEMA6B</em> show potential roles in immune modulation and epithelial plasticity. Enrichment analyses confirm the involvement of these genes in extracellular matrix (ECM) remodeling, collagen degradation, integrin signaling, receptor tyrosine kinase signaling, and cytokine signaling. Although the findings remain correlative, they point to a shared molecular landscape underlying fibrotic and neoplastic transformation. Future studies integrating longitudinal cohorts and functional validation are essential to refine biomarker strategies and therapeutic targets for patients with fibrotic lung disease at risk of malignancy.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102333"},"PeriodicalIF":0.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arylamine N-acetyltransferase 1 knockout in immortalized human bronchial cells results in a reduction of cellular growth","authors":"Sandra S. Diven ,&nbsp;Kate Tarvestad-Laise ,&nbsp;David W. Hein ,&nbsp;James T.F. Wise","doi":"10.1016/j.genrep.2025.102332","DOIUrl":"10.1016/j.genrep.2025.102332","url":null,"abstract":"<div><div>Arylamine <em>N</em>-acetyltransferase 1 (NAT1) is a xenobiotic metabolizing enzyme. NAT1 has recently been proposed to have a non-canonical role in cancer cells, where NAT1 knockout (KO) results in reduced cell growth, cancer properties, and altered mitochondria metabolism. The non-canonical role of NAT1 in human lung cells remains unknown. This study aimed to understand if the loss of NAT1 in human bronchial cells, both epithelial (BEP2D) and fibroblast (WTHBF-6), impacted cell growth. We constructed cell lines stably expressing Cas9 and then inserted two different guide RNA (gRNA) sequences for NAT1 into BEP2D cells and WTHBF-6 cells. We expanded colonies of both cell lines for each gRNA and confirmed the loss of NAT1 by measuring the <em>N</em>-acetylation of a NAT1 selective substrate (p-aminobenzoic acid). We measured cell growth via growth curves and colony formation. We also screened the karyotype of each clone to determine if NAT1 had an impact on genomic stability. We found a reduction in the growth of NAT1 KO cells compared to parental cells. Interestingly, there was no change in colony number for NAT1 KO cells, but there was a reduction in the colony cell density (qualitatively observed) for these cells. NAT1 knockout did not induce genomic instability. These data provide further evidence suggesting that NAT1 has a non-canonical role outside of substrate acetylation, and results indicate that NAT1 KO reduces cell growth of non-tumorigenic human lung cells.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102332"},"PeriodicalIF":0.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF2BP2 gene showed immunophenotype-dependent overexpression in acute myeloid leukemia patients","authors":"Mustafa A. Bashi ,&nbsp;Noor W. Ali ,&nbsp;Dhay A. Azeez ,&nbsp;Maryam H. Ibrahem ,&nbsp;Mohammed K. Al-Qayyim ,&nbsp;Ali H. Ad'hiah","doi":"10.1016/j.genrep.2025.102331","DOIUrl":"10.1016/j.genrep.2025.102331","url":null,"abstract":"<div><div><em>IGF2BP2</em> (insulin-like growth factor 2 mRNA-binding protein 2) is a gene that encodes a protein (IGF2BP2) involved in promoting RNA stability, facilitating RNA translation, and regulating post-transcriptional processes. Recent evidence indicates that <em>IGF2BP2</em> is overexpressed in acute myeloid leukemia (AML). However, the association between <em>IGF2BP2</em> expression and genetic abnormalities in AML remains poorly understood. Furthermore, <em>IGF2BP2</em> expression across AML subtypes and immunophenotypes has yet to be characterized. In this retrospective study, <em>IGF2BP2</em> mRNA expression was evaluated in 106 AML patients, with a focus on understanding the relationship between <em>IGF2B</em>P2 expression and disease subtype, genetic abnormalities, and peripheral blood immunophenotypes. <em>IGF2BP2</em> expression (relative fold change; 2^−ΔΔCt) in peripheral blood was determined using quantitative PCR analysis. Results revealed that <em>IGF2BP2</em> was overexpressed in AML patients (median: 1.20; interquartile range 25–75 %: 0.73–2.39; range: 0.51–4.25). <em>IGF2BP2</em> overexpression was more pronounced in cases positive for cluster of differentiation (CD) 4, CD11b, CD35, CD36, cTdT (cytoplasmic terminal deoxynucleotidyl transferase), and IREM2 (immune receptor expressed by myeloid cells 2) than in cases negative for the corresponding markers, but the adjusted probability for multiple comparisons was not statistically significant (0.14, 0.07, 0.21, 0.07, 0.112, and 0.07, respectively). <em>IGF2BP2</em> expression levels also showed variations based on gender, age, genetic abnormality, and disease subtype, but without statistical significance. In conclusion, expression of <em>IGF2BP2</em> showed up-regulated levels in AML, particularly in patients positive for the immunophenotypic markers CD4, CD11b, CD35, CD36, cTdT, and IREM2. <em>IGF2BP2</em> expression may be affected by gender, age, genetic abnormalities, and AML subtypes.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102331"},"PeriodicalIF":0.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the genetic implications of TAGAP 3′UTR non-coding polymorphism in rheumatoid arthritis: A case-control and bioinformatics approach","authors":"M. Shri Preethi ,&nbsp;V. Shamala ,&nbsp;N. Balaji ,&nbsp;S. Asha Devi","doi":"10.1016/j.genrep.2025.102330","DOIUrl":"10.1016/j.genrep.2025.102330","url":null,"abstract":"<div><div>Rheumatoid Arthritis (RA) is a chronic inflammatory disease that affects joints and causes bone deformities. Single Nucleotide Polymorphisms (SNPs) within the T-cell activation Rho GTPase-activating protein (TAGAP) gene increase the risk of RA development. High expression of the TAGAP gene has been observed in RA patients. High-Resolution Melting Analysis (HRMA) technique was used to genotype TAGAP rs4709267 (A/G) SNP, located in the 3′Untranslated Region (UTR). Further, to investigate the impact of the rs4709267 SNP on the TAGAP gene expression level, the TAGAP 3′UTR sequences with wild (A) and variant (G) alleles were cloned into the pGL3-SV40 vector. The cloned vectors were transfected into HeLa cells, and the luciferase reporter assay was performed using the pRL-SV40 (Renilla plasmid) vector as an internal control. The HRMA result reveals that the TAGAP 3′UTR rs4709267 SNP-G allele was statistically associated with RA in the Indian population. Also, a significant increase (<em>p</em> &lt; 0.05) in the expression of luciferase level suggests that the rs4709267 SNP may be associated with RA by affecting the TAGAP gene expression levels.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102330"},"PeriodicalIF":0.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome analysis of Pseudomonas spp. CPA-7, a strain with potential as a biocontrol agent","authors":"Cyrelys Collazo ,&nbsp;Jose Francisco Sanchez-Herrero ,&nbsp;Rui Alves ,&nbsp;Julio Rozas ,&nbsp;Isabel Alegre ,&nbsp;Abdelrhaman Eleiwa ,&nbsp;Inmaculada Viñas","doi":"10.1016/j.genrep.2025.102326","DOIUrl":"10.1016/j.genrep.2025.102326","url":null,"abstract":"<div><div>We report the whole genome sequence of CPA-7, a strain isolated from apple surface and classified as <em>Pseudomonas graminis,</em> that has shown antagonistic activity against pathogenic bacteria in several food matrices. Its genome comprises 5,786,948 bp, with 60.5 % average of C + G content. From the 5122 predicted protein coding sequences (CDSs), 4703 (91.8 %) were functionally annotated. Comparative genomic analyses using 366 fully sequenced <em>Pseudomonas</em> strains placed CPA-7 within the <em>P. lutea</em> group, more related to <em>P. graminis</em> UASWS1507. However, ANI values in respect to the other fully sequenced <em>P. graminis</em> (91–92 %)<em>,</em> including the type strain DSM11363, were below the intraspecific bacterial threshold (95 %). Whole genomic digital DNA-DNA hybridization in the Type Strain Genome Server also gave a below threshold score for <em>P. graminis</em> (47.7 %), suggesting the need for revision of this taxon. BLAST analyses of 16S rRNA showed &gt;99 % identity with other <em>Pseudomonas</em> spp. while the <em>rpoD</em> amplified sequence revealed a 100 % similarity with <em>Pseudomonas</em> sp. Irchel 1A17. Single orthologs analysis unraveled 341 CDSs unique to CPA-7 compared to the rest of <em>P. graminis</em> strains including genes involved in transport, adherence, and adaptability. Genome mining uncovered genes potentially involved in biological control, and plant growth promoting activities which corresponded to in vitro activities such as the production of siderophores, 1-aminocyclopropane-1-carboxylate deaminase, and Indole-3-acetic acid as well as Phosphorous solubilization. Furthermore, multiple genes associated with chemotaxis, colonization, and metabolic plasticity, unravel the genetic basis for the potentialities of CPA-7 as a biocontrol agent, opening several lines for further investigation.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102326"},"PeriodicalIF":0.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-silico analysis of non-synonymous SNPs in insulin binding site of insulin receptor and screening in Indian PCOS women","authors":"Prayukta Padelkar ,&nbsp;Himaja Kuppachi ,&nbsp;Anuradha V ,&nbsp;Deekshitha Dinakar ,&nbsp;Viswas Kathireshakumar ,&nbsp;Sharini S ,&nbsp;Monisha Mohan ,&nbsp;Usha Balasundaram","doi":"10.1016/j.genrep.2025.102327","DOIUrl":"10.1016/j.genrep.2025.102327","url":null,"abstract":"<div><div>Insulin resistance (IR) is one of the major patho-physiology of polycystic ovary syndrome (PCOS) among women of reproductive age. Generally, PCOS women with IR incur metabolic syndrome consisting of high blood glucose, cholesterol, and insulin levels due to mutations in the insulin receptor gene. Our study aimed at identifying putative deleterious nsSNPs on the insulin binding site of the <em>INSR</em> gene using in silico tools and screening these SNPs in the Indian PCOS women diagnosed with metabolic syndrome. The <em>INSR</em> gene with a total of 7142 SNPs were retrieved from dbSNP, with six non-synonymous SNPs found at the insulin-binding site. Three out of six nsSNPs (i.e. rs1294314902, rs1568448566, rs1353116498) were pathogenic as predicted using SIFT, PROVEAN, PolyPhen2, SNAP2 tools, whilst the stability and structural changes were validated using Project HOPE, MutPred2, and MuPro tools. Further, structural modelling, docking, and simulation were employed, which resulted in a wide difference between the docking scores of insulin ligand binding with wild-type and mutant proteins, indicating potential deleteriousness of the nsSNPs and their functional and structural implications. Further, SNPs were examined by utilizing Sanger sequencing using the primers specific to the insulin binding site of the <em>INSR</em> gene in sixty-three PCOS women diagnosed with high blood glucose and insulin resistance. However, none of these nsSNPs were found in the cohorts.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102327"},"PeriodicalIF":0.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}