{"title":"Unravelling the interplay of antimicrobial resistance and stress response in the saline desert metagenomes of Gujarat, India","authors":"R. Sahana , Vishal Mevada , Urvisha Beladiya , Dhaval Prajapati , Himani Gandhi , Rajesh Patel","doi":"10.1016/j.genrep.2025.102216","DOIUrl":"10.1016/j.genrep.2025.102216","url":null,"abstract":"<div><div>The metagenomic analysis of the present study states the intricate community of salt-tolerant bugs living in saline soils from Kutch, Gujarat. Metagenomics sequencing has already been explored in this region for community analysis. However, we analyzed the metagenome of a saline desert and compared it with publicly available published metagenomes to identify common antimicrobial resistance found in the saline desert. The bioinformatics-based analysis revealed the presence of various antibiotic resistance (AMR) genes in <em>Escherichia coli</em> EF-Tu mutants, which confer resistance to several compounds, including Pulvomycin, FosG, rsmA, qacJ, and qacG. Additionally, the vanW gene in the vanI cluster and the vanY gene in the vanM cluster were identified. These mutants exhibit different resistance mechanisms, such as antibiotic inactivation (VanA — VIM-VIA), alteration of antibiotic targets (cfr and VanB), and the involvement of antibiotic efflux pumps, etc. The prevalence of AMR genes related to efflux pump indicates the importance of this genes (copR, bcrA, cesC, merA, narA, tetA, trxLHR and yfeB) toward salt tolerance and antibiotic resistance. This effect was robust even when human impacts were not substantial, illustrating the overwhelming adaptability of these organisms. The variable presence of these genes throughout the samples highlights an environmental effect on their distribution, suggesting a resistance mechanism. This work paves the way to understanding antimicrobial resistance genes produced in these pristine, human-untouched places.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102216"},"PeriodicalIF":1.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767804","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}
Gene ReportsPub Date : 2025-04-02DOI: 10.1016/j.genrep.2025.102214
Haidar J. Muhammed , Marwa M. Al-Attar , Zainab Fayadh Shubrem , Mohanad Kareem Aneed Al-Saedi , Maryam Qasim Mohammed
{"title":"Quantitative real-time PCR analysis of circulating MicroRNA levels in blood samples from pediatric patients with epilepsy","authors":"Haidar J. Muhammed , Marwa M. Al-Attar , Zainab Fayadh Shubrem , Mohanad Kareem Aneed Al-Saedi , Maryam Qasim Mohammed","doi":"10.1016/j.genrep.2025.102214","DOIUrl":"10.1016/j.genrep.2025.102214","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy in childhood is common in the first year and its incidence decreases with age increase. The prevalence of epilepsy in Iraq was 1.0 per 1000 children according to a previous investigation. MicroRNAs play crucial roles in various biological processes, including brain development and function, and have emerged as potential key players in the complex pathophysiology of epilepsy. This study aimed to investigate the expression levels of miRNAs in their mature forms including <em>miR-30a-5p</em> and <em>miR-577</em>, in epilepsy patients and to explore their potential as biomarkers for the disease.</div></div><div><h3>Methods</h3><div>Eighty participants were enrolled in the study classified as (<em>n</em> = 40) Epilepsy patients along with (n = 40) as healthy controls (HCs). The miRNA was extracted from whole blood, converted to complementary DNA (cDNA) using a specialized kit, and quantified using quantitative real-time PCR (qRT-PCR) for <em>miR-30a-5p, miR-577,</em> and the reference gene <em>snRNA-U6</em>.</div></div><div><h3>Results</h3><div>The results revealed a significant upregulation of <em>miR-30a-5p</em> in epilepsy patients compared to healthy controls with (<em>p</em>-value, 0.01). The <em>miR-577</em> expression did not differ between groups (<em>p</em>-value, 0.2). A weak negative correlation between the two miRNAs was observed, suggesting a potential inverse correlation. Receiver Operating Characteristic (ROC) curve analysis indicated that <em>miR-30a-5p</em> may serve as a biomarker for epilepsy.</div></div><div><h3>Conclusion</h3><div>This study suggests that <em>miR-30a-5p</em>, showing upregulation and according to the ROC curve may act as an early epilepsy detection biomarker. Conversely, miR-577, despite a decrease in expression, is deemed unsuitable as a biomarker due to its lack of statistical significance and poor diagnostic performance.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102214"},"PeriodicalIF":1.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767803","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}
Gene ReportsPub Date : 2025-04-02DOI: 10.1016/j.genrep.2025.102215
Rahul Kumar Vempati, Rama Rao Malla
{"title":"Sanguinarine targets the catalytic domain of MMP-9: Molecular dynamics and in vitro studies in MDA-MB 468 breast cancer cells","authors":"Rahul Kumar Vempati, Rama Rao Malla","doi":"10.1016/j.genrep.2025.102215","DOIUrl":"10.1016/j.genrep.2025.102215","url":null,"abstract":"<div><div>Matrix metalloproteinase 9 (MMP9) belongs to a group of endopeptidases. It is functionally involved in the proteolytic degradation of extracellular matrix proteins in various pathophysiological conditions. MMP9 is overexpressed in several cancers and is crucial for metastatic progression of triple negative breast cancer (TNBC). Because of its etiological significance in TNBC, it is considered a potential therapeutic target. In this study, our <em>in silico</em> studies demonstrated that Sanguinarine (SAN) could directly binds to catalytic domain (CD) of MMP9 <em>via</em> key amino acid residues involved in its enzymatic function. Docking studies using CB Dock, PyRx, Seam Dock, and 1-click docking have predicted that SAN binds the MMP9-CD with a binding affinity of −8.5 kcal/mol. Further, our docking studies also showed that structural derivatives of SAN bind to the CD of MMP9 with almost the same affinity as SAN. Structural derivatives 10-hydroxydihydrosanguinarine, dihydrosanguinarine, ethoxysanguinarine, and norsanguinarine were found to bind the MMP9-CD with binding affinities −8.3 kcal/mol,-8.2 kcal/mol,-7.5 kcal/mol, and -8.3 kcal/mol, respectively. Molecular dynamics simulation studies strongly validated our docking results showing that SAN forms stable interactions with critical amino acid residues Leu188, Tyr393, and Met 422 within the catalytic site of MMP9. Further, the effect of SAN on activity and expression of MMP9 was validated in MDA-MB 468, a TNBC cell line, along with known MMP9 inhibitor, Amentoflavone (AMF). Both SAN and AMF reduced the viability and proliferation of TNBC cells by damaging the cell integrity. On the whole, our study shows that SAN can directly inhibit MMP9 by binding to its CD and viability of breast cancer cells.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102215"},"PeriodicalIF":1.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777249","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}
Gene ReportsPub Date : 2025-03-31DOI: 10.1016/j.genrep.2025.102213
J. Akshaya, Dhayanand John Victor, Devapriya Appukuttan, Santhosh Venkadassalapathy, Sangeetha Subramanian, P.S.G. Prakash
{"title":"Comparative evaluation of macrophage polarization markers- nitric oxide, sCD163 and miRNA-21 in the saliva of healthy, gingivitis and periodontitis patients with and without type 2 diabetes mellitus: A case-control study","authors":"J. Akshaya, Dhayanand John Victor, Devapriya Appukuttan, Santhosh Venkadassalapathy, Sangeetha Subramanian, P.S.G. Prakash","doi":"10.1016/j.genrep.2025.102213","DOIUrl":"10.1016/j.genrep.2025.102213","url":null,"abstract":"<div><h3>Background</h3><div>M1/M2 macrophage phenotypes are crucial for periodontal tissue homeostasis, and their balance is modulated by micro-RNAs. This study sought to assess the potential of nitric oxide (NO), sCD163, and miRNA-21 to serve as diagnostic biomarkers.</div></div><div><h3>Materials and methods</h3><div>52 subjects categorised into 4 groups - Group A: systemically and periodontally healthy; Group B: systemically healthy with gingivitis; Group C: Stage- III or IV Periodontitis without Type 2 Diabetes Mellitus(T2DM) and Group D: stage III/IV periodontitis with T2DM.Saliva was analyzed for sCD163 using ELISA, NO by colorimetric assay and miRNA-21 by real time qPCR.</div></div><div><h3>Results</h3><div>Group C and D had higher concentration of sCD163 and NO, when compared to Groups A and B with the difference being statistically significant (<em>p</em> < 0.001). The miRNA-21 CT values were highest in group B while it was lowest in group D, with this difference being significant (p < 0.001). Higher miRNA-21 fold change was seen in group C which however was not statistically significant on comparing between the groups. sCD163 and NO values showed a positive correlation and miRNA-21 CT values showed a negative correlation with clinical parameters which was statistically significant (<em>p</em> < 0.05). sCD163 and NO showed a significant positive correlation with each other, whereas miRNA-21 CT showed significant negative correlation with sCD163 (p < 0.05).</div></div><div><h3>Conclusions</h3><div>Dysregulated macrophage polarization may play a prime role in the pathogenesis of periodontitis with or without diabetes mellitus. sCD163, NO, and miRNA-21 could be potential diagnostic biomarkers for evaluating macrophage polarization and periodontitis severity, which will however need to be confirmed through longitudinal trials.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102213"},"PeriodicalIF":1.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791837","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}
Gene ReportsPub Date : 2025-03-28DOI: 10.1016/j.genrep.2025.102210
Yeganeh Hajizadeh , Mana Oloomi
{"title":"CRISPR interference for blaNDM-1 and blaOXA-48 genes suppression in carbapenemase-resistant Klebsiella pneumoniae strains","authors":"Yeganeh Hajizadeh , Mana Oloomi","doi":"10.1016/j.genrep.2025.102210","DOIUrl":"10.1016/j.genrep.2025.102210","url":null,"abstract":"<div><div>One treatment option for multidrug-resistant strains, such as carbapenemase-producing <em>Klebsiella pneumoniae</em>, is the CRISPR interference (CRISPRi) technique, developed to address issues caused by these pathogens. This system includes a gRNA and a dCas9. This study investigates the effectiveness of the CRISPRi system in reducing meropenem resistance in <em>K. pneumoniae</em> harboring β-lactamase strains, specifically the <em>bla</em><sub>NDM-1</sub> and <em>bla</em><sub>OXA-48</sub> genes, both separately and simultaneously, by optimizing sgRNA designs. We designed and incorporated two optimal sgRNAs, which were then cloned into a pJMP1363 plasmid with the CRISPRi system to target the expression of the <em>bla</em><sub>NDM-1</sub> and <em>bla</em><sub>OXA-48</sub> genes separately and simultaneously. Antimicrobial resistance was evaluated using the MIC test, and gene expression was measured with qRT-PCR. The MIC test results showed a decrease in meropenem resistance in <em>K. pneumoniae</em> strains carrying the pJMP1363 construct (sgRNA+). The qRT-PCR analysis indicated a reduction in mRNA expression for strains carrying the construct (sgRNA+), with a 67-fold and 31-fold decrease for <em>bla</em><sub>OXA-48</sub> and <em>bla</em><sub>NDM-1</sub>, respectively, and a 100-fold decrease for strains with both <em>bla</em><sub>OXA-48</sub> and <em>bla</em><sub>NDM-1</sub>. The decrease in meropenem resistance was more noticeable in strains harboring both resistance genes compared to strains with either gene alone. The study also demonstrated that both sgRNA<sub>OXA-48</sub> and sgRNA<sub>NDM-1</sub>, targeting the non-template and template strands of the respective genes, effectively lowered transcription levels of the target genes. Notably, sgRNA<sub>OXA-48</sub> significantly reduced the expression of the <em>bla</em><sub>OXA-48</sub> gene.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102210"},"PeriodicalIF":1.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726171","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":"Bioinformatic tools for CRISPR-mediated genome editing","authors":"Fatemeh Gila , Shayan Shakeri , Somayeh Khoddam , Zahra Jamali , Ali Saber Sichani , Zeinab Dehghan , Jafar Fallahi","doi":"10.1016/j.genrep.2025.102204","DOIUrl":"10.1016/j.genrep.2025.102204","url":null,"abstract":"<div><div>The groundbreaking gene-editing tool CRISPR-Cas9 has revolutionized molecular biology. It is a method that enables scientists to precisely alter the DNA of living cells, which holds great promise for treating genetic illnesses. The Cas9 protein and a guide RNA (gRNA) are the two critical parts of the CRISPR-Cas9 system. While the gRNA guides the Cas9 protein to the appropriate region in the genome, the Cas9 protein functions as a pair of molecular scissors, cutting the DNA at a specific location. In recent years, several databases have been created to assist researchers in designing efficient gRNAs. These databases provide information on the specificity and efficiency of various gRNAs and tools for designing custom gRNAs. This review article will go over the most beneficial and recent databases for gRNA design that are now accessible. These databases are crucial for attaining effective and precise gene editing and therapy using the CRISPR-Cas9 system.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102204"},"PeriodicalIF":1.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143716067","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}
Gene ReportsPub Date : 2025-03-26DOI: 10.1016/j.genrep.2025.102202
Doha El-sayed Ellakwa , Ahmed Said Mansour , Rimon Gorgui , Hala Mohamed Banksle
{"title":"Cerebrolysin in post-TBI recovery: Pharmacology and clinical evidence","authors":"Doha El-sayed Ellakwa , Ahmed Said Mansour , Rimon Gorgui , Hala Mohamed Banksle","doi":"10.1016/j.genrep.2025.102202","DOIUrl":"10.1016/j.genrep.2025.102202","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) affects millions of individuals globally on an annual basis, with present therapeutic approaches primarily concentrating on the management of symptoms and the prevention of secondary injuries. Affected individuals frequently encounter enduring cognitive and functional deficits, which substantially diminish their overall quality of life. Nonetheless, in spite of progress made in acute medical care, efficacious treatments aimed at facilitating neurorecovery and enhancing long-term outcomes remain limited. Consequently, researchers are investigating innovative therapeutic interventions, with cerebrolysin emerging as a notable candidate. This neuropeptide formulation has exhibited neuroprotective and neurorestorative capabilities in preclinical investigations, fostering neuroplasticity, augmenting neurogenesis, and mitigating neuronal injury in TBI models. Furthermore, clinical trials have revealed potential advantages for human patients. This review aims to elucidate the mechanisms of action of cerebrolysin and its prospective function in TBI recovery, scrutinizing preclinical evidence pertaining to its neuroprotective effects and facilitation of brain repair. Additionally, we assess clinical findings from randomized controlled trials, which indicate enhancements in motor skills, cognitive abilities, and overall functional outcomes among TBI patients administered cerebrolysin. While preliminary results are promising, we examine existing evidence deficiencies and domains necessitating additional inquiry, encompassing the identification of patient subpopulations that are most likely to derive benefit, the optimization of dosage protocols, and the execution of more extensive, multi-center clinical trials. This thorough analysis aspires to clarify the potential of cerebrolysin as a therapeutic modality and to inform subsequent research endeavors in this vital domain.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102202"},"PeriodicalIF":1.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767802","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}
Gene ReportsPub Date : 2025-03-26DOI: 10.1016/j.genrep.2025.102207
Uroosa Ejaz , Hassan Ghayas , Sabiha Yousuf , Ayaz Taj , Muhammad Sohail
{"title":"Decoding whole genome of an industrially important thermophilic bacterium Anoxybacteroides rupiense","authors":"Uroosa Ejaz , Hassan Ghayas , Sabiha Yousuf , Ayaz Taj , Muhammad Sohail","doi":"10.1016/j.genrep.2025.102207","DOIUrl":"10.1016/j.genrep.2025.102207","url":null,"abstract":"<div><div><em>Anoxybacteroides</em> (previously <em>Anoxybacillus)</em> is a relatively new genus, proposed in the year 2000, and comprised of many species which are reported to play a vital role in bioprocessing and bioremediation. Very few reports described the whole genome sequence (WGS) of this genus. Therefore, in this study, WGS of a new strain, UE27, was analyzed. This thermophilic strain was previously isolated from the crocodile pond of Manghopir, Karachi. The genome of <em>A. rupiense</em> (previously <em>Anoxybacillus rupiensis</em>) UE27 was submitted to NCBI GenBank with the accession number JBHLFH010000000.1. Genome size was found to be 3,771,980 bp with 76 contigs and 42.33 % GC content. Among 3789 genes, 3708 were found as protein coding genes. Interestingly, intake prophage genome was found which has not been previously reported in <em>A. rupiense</em>. The prophage region contained 68 coding sequence among which 48 were identified as phage-related genes with 40.09 % GC content. The xylan degradation genes were also annotated in the genome. Moreover, many genes responsible for azo dye degradation, heavy metal detoxification and hydrocarbon removal were found in the genome. Conclusively, this study provided insight into gene repertoire of <em>A. rupiense</em> and a basis for the potential application of this thermophilic bacterium in bioremediation and bioprospecting.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102207"},"PeriodicalIF":1.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739019","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}
Gene ReportsPub Date : 2025-03-26DOI: 10.1016/j.genrep.2025.102201
Di Zhang , Xiaoping Ding , Wenyu Li , Lingling Li , Gongye Cheng , Jianghui Yu , Zhijun Wang , Houxiong Wu , Cheng Zheng , Ling Liu , Lanxin Liu , Meijuan Duan , Dingyang Yuan , Citao Liu
{"title":"Mechanisms underpinning cold tolerance in indica hybrid rice: Insights for northern adaptation","authors":"Di Zhang , Xiaoping Ding , Wenyu Li , Lingling Li , Gongye Cheng , Jianghui Yu , Zhijun Wang , Houxiong Wu , Cheng Zheng , Ling Liu , Lanxin Liu , Meijuan Duan , Dingyang Yuan , Citao Liu","doi":"10.1016/j.genrep.2025.102201","DOIUrl":"10.1016/j.genrep.2025.102201","url":null,"abstract":"<div><div>Cold tolerance is essential for rice cultivation in northern regions, where low temperatures limit yield potential. This study explores the cold tolerance mechanisms in Liyouyuchi (LYYC), an <em>indica</em> hybrid rice developed by crossing Ruifeng S with R1053, LYYC demonstrated superior cold tolerance, outperforming local varieties with a 16.5 % yield increase in Harbin and a yield of 12.35 t/ha in Jilin in 2023. Under cold stress, LYYC exhibited a lower levels of reactive oxygen species (ROS) accumulation and significantly higher survival rate compared to its parental lines. Genetic analysis identifies several key loci associated with cold tolerance in LYYC, including beneficial allelic variants in <em>GSTZ2</em>, <em>COG1</em>, <em>qCTB7</em> and <em>Ctb1</em>. Notably, <em>GSTZ2</em> and <em>Ctb1</em> exhibited high parent heterosis, while <em>qCTB7</em> displayed extreme parent heterosis under cold stress, with expression levels significantly higher than both the paternal and maternal lines. The favorable allelic variations in these genes position LYYC as a promising resource for breeding cold-resistant rice varieties. These findings provide valuable insights into the genetic mechanisms of cold tolerance, contributing to the development of rice cultivars better adapted to northern climates and cold-induced stress.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102201"},"PeriodicalIF":1.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735281","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}
Gene ReportsPub Date : 2025-03-25DOI: 10.1016/j.genrep.2025.102209
Shubhashree Parimita, Amitava Das, Sanjoy Samanta
{"title":"Reduced expression of insulin like growth factor-2 mRNA binding protein 2 (IMP2) elevates TAZ via IMP3 in triple-negative breast cancer","authors":"Shubhashree Parimita, Amitava Das, Sanjoy Samanta","doi":"10.1016/j.genrep.2025.102209","DOIUrl":"10.1016/j.genrep.2025.102209","url":null,"abstract":"<div><div>Insulin like growth factor-2 mRNA binding proteins IMP2 and IMP3 are usually expressed in aggressive triple-negative breast cancer (TNBC). Although, IMP3 plays a pro-tumorigenic role in breast tumors, function of IMP2 is less clear. Therefore, the objective of this study is to understand the functions of IMP2 in breast cancer. Using published mRNA and proteomic databases, we show that expressions of IMP2 and IMP3 correlate well in breast tumors. One of the important mechanisms by which IMP3 contributes to TNBC progression is its ability to activate TAZ oncoprotein via LATS1 and WNT5B. Surprisingly, short hairpin RNA (shRNA) mediated depletion of IMP2 protein increased TAZ and WNT5B expression in TNBC cells. We also noticed a decrease in phospho-LATS1. This observation is surprising because both IMP2 and IMP3 proteins are structurally very similar and are expressed together in TNBC. Moreover, we discovered that IMP2 depletion increased IMP3 expression which in turn enhanced TAZ and WNT5B level. Although both IMP2 & IMP3 interacts physically as evident from the co-immunoprecipitation experiment, the mechanism behind this reciprocal regulation is not clear at this point. Further, our analysis of a proteomic database identified proteins (notably SOX10, S100A9, SLC7A5 and ARG1) that are significantly elevated in TNBCs that express relatively higher IMP2 (IMP2<sup>high</sup>) compared to IMP2<sup>low</sup> tumors. Despite a strong positive correlation with IMP2, expressions of these genes are also increased in IMP2-depleted cells. Importantly, these genes are associated with poor patients survival. In conclusion, IMP2 seems to play a tumor suppressive role in TNBC cells.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102209"},"PeriodicalIF":1.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143716066","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}