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Sanguinarine targets the catalytic domain of MMP-9: Molecular dynamics and in vitro studies in MDA-MB 468 breast cancer cells 血氨酸靶向MMP-9的催化结构域:MDA-MB 468乳腺癌细胞的分子动力学和体外研究
IF 1
Gene Reports Pub Date : 2025-04-02 DOI: 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,&nbsp;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}
引用次数: 0
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 健康人、牙龈炎和牙周炎合并和不合并2型糖尿病患者唾液中巨噬细胞极化标志物一氧化氮、sCD163和miRNA-21的比较评价:一项病例对照研究
IF 1
Gene Reports Pub Date : 2025-03-31 DOI: 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,&nbsp;Dhayanand John Victor,&nbsp;Devapriya Appukuttan,&nbsp;Santhosh Venkadassalapathy,&nbsp;Sangeetha Subramanian,&nbsp;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> &lt; 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 &lt; 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> &lt; 0.05). sCD163 and NO showed a significant positive correlation with each other, whereas miRNA-21 CT showed significant negative correlation with sCD163 (p &lt; 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}
引用次数: 0
MicroRNA-34a enhances immune response and suppresses PI3K/AKT signaling through targeting PD-L1 in triple-negative breast cancer MicroRNA-34a在三阴性乳腺癌中通过靶向PD-L1增强免疫应答,抑制PI3K/AKT信号
IF 1
Gene Reports Pub Date : 2025-03-30 DOI: 10.1016/j.genrep.2025.102211
Vahid Tavakolpour , Mahboubeh Safari-Kharkeshi , Hamid Reza Soleimanpour-Lichaei , Mossa Gardaneh , Fatemeh Kouhkan
{"title":"MicroRNA-34a enhances immune response and suppresses PI3K/AKT signaling through targeting PD-L1 in triple-negative breast cancer","authors":"Vahid Tavakolpour ,&nbsp;Mahboubeh Safari-Kharkeshi ,&nbsp;Hamid Reza Soleimanpour-Lichaei ,&nbsp;Mossa Gardaneh ,&nbsp;Fatemeh Kouhkan","doi":"10.1016/j.genrep.2025.102211","DOIUrl":"10.1016/j.genrep.2025.102211","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) remains a significant clinical challenge due to its aggressive nature and limited therapeutic options. PD-L1 and the PI3K/AKT signaling pathway have previously been shown to form a feed-forward loop that promotes tumor progression and immune evasion. This study investigates miR-34a as a key regulator of this interaction, integrating comprehensive bioinformatics analysis with experimental validation. Weighted gene co-expression network analysis (WGCNA) of 255 TNBC samples revealed regulatory links between PD-L1 and PI3K signaling, while the analysis of 50 paired clinical samples confirmed an inverse correlation between miR-34a and PD-L1 expression. Luciferase reporter assays validated miR-34a as a direct regulator of PD-L1, leading to its downregulation and suppression of the PI3K/AKT signaling pathway in MDA-MB-231 cells transduced with a miR-34a-expressing lentivirus, as confirmed by Western blot analysis. Functional assays showed that miR-34a reduces cell viability, induces apoptosis, and causes G1 cell cycle arrest while also downregulating the stemness-associated transcription factors Nanog and Oct-4, suggesting a loss of tumor plasticity. Furthermore, co-culture experiments with PBMCs demonstrated that miR-34a enhances anti-tumor immune responses, as indicated by increased IL-2, IFN-γ, and TNF-α expression and IL-10 downregulation. Our results characterize miR-34a as a potential tumor-suppressor miRNA in TNBC that regulates both immune responses and key cancer hallmarks by targeting PD-L1 and suppressing the PI3K/AKT signaling pathway. These findings underscore miR-34a as a promising candidate for developing a multifaceted, miRNA-based immunotherapeutic approach for TNBC.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"40 ","pages":"Article 102211"},"PeriodicalIF":1.0,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886153","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}
引用次数: 0
CRISPR interference for blaNDM-1 and blaOXA-48 genes suppression in carbapenemase-resistant Klebsiella pneumoniae strains CRISPR干扰对碳青霉烯酶耐药肺炎克雷伯菌blaNDM-1和blaOXA-48基因的抑制
IF 1
Gene Reports Pub Date : 2025-03-28 DOI: 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 ,&nbsp;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}
引用次数: 0
Bioinformatic tools for CRISPR-mediated genome editing crispr介导的基因组编辑的生物信息学工具
IF 1
Gene Reports Pub Date : 2025-03-26 DOI: 10.1016/j.genrep.2025.102204
Fatemeh Gila , Shayan Shakeri , Somayeh Khoddam , Zahra Jamali , Ali Saber Sichani , Zeinab Dehghan , Jafar Fallahi
{"title":"Bioinformatic tools for CRISPR-mediated genome editing","authors":"Fatemeh Gila ,&nbsp;Shayan Shakeri ,&nbsp;Somayeh Khoddam ,&nbsp;Zahra Jamali ,&nbsp;Ali Saber Sichani ,&nbsp;Zeinab Dehghan ,&nbsp;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}
引用次数: 0
Cerebrolysin in post-TBI recovery: Pharmacology and clinical evidence 脑溶血素在脑外伤后恢复中的作用:药理学和临床证据
IF 1
Gene Reports Pub Date : 2025-03-26 DOI: 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 ,&nbsp;Ahmed Said Mansour ,&nbsp;Rimon Gorgui ,&nbsp;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}
引用次数: 0
Decoding whole genome of an industrially important thermophilic bacterium Anoxybacteroides rupiense 解码工业上重要的嗜热细菌红宝石无氧杆菌的全基因组
IF 1
Gene Reports Pub Date : 2025-03-26 DOI: 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 ,&nbsp;Hassan Ghayas ,&nbsp;Sabiha Yousuf ,&nbsp;Ayaz Taj ,&nbsp;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}
引用次数: 0
Mechanisms underpinning cold tolerance in indica hybrid rice: Insights for northern adaptation 杂交籼稻耐寒性的机制:对北方适应性的认识
IF 1
Gene Reports Pub Date : 2025-03-26 DOI: 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 ,&nbsp;Xiaoping Ding ,&nbsp;Wenyu Li ,&nbsp;Lingling Li ,&nbsp;Gongye Cheng ,&nbsp;Jianghui Yu ,&nbsp;Zhijun Wang ,&nbsp;Houxiong Wu ,&nbsp;Cheng Zheng ,&nbsp;Ling Liu ,&nbsp;Lanxin Liu ,&nbsp;Meijuan Duan ,&nbsp;Dingyang Yuan ,&nbsp;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}
引用次数: 0
Reduced expression of insulin like growth factor-2 mRNA binding protein 2 (IMP2) elevates TAZ via IMP3 in triple-negative breast cancer 胰岛素样生长因子-2 mRNA结合蛋白2 (IMP2)在三阴性乳腺癌中的表达减少通过IMP3升高TAZ
IF 1
Gene Reports Pub Date : 2025-03-25 DOI: 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,&nbsp;Amitava Das,&nbsp;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 &amp; 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}
引用次数: 0
miRNAs: Biosynthesis, mechanism of action, and applications in biological systems mirna:生物合成、作用机制及其在生物系统中的应用
IF 1
Gene Reports Pub Date : 2025-03-25 DOI: 10.1016/j.genrep.2025.102208
Kun Liu, Weiwei Cai
{"title":"miRNAs: Biosynthesis, mechanism of action, and applications in biological systems","authors":"Kun Liu,&nbsp;Weiwei Cai","doi":"10.1016/j.genrep.2025.102208","DOIUrl":"10.1016/j.genrep.2025.102208","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that are ubiquitously distributed across eukaryotic organisms. Through complementary base pairing with target mRNA, miRNAs have been demonstrated to regulate gene expression by inducing gene silencing. This comprehensive review provides an overview of the biosynthesis and pathways of miRNAs, their mechanisms of action in various organisms, and their diverse applications in animal diseases, agriculture, environmental toxicology, drug development, cellular repair, and nutritional sciences. The miRNA gene undergoes a sophisticated processing cascade, involving RNA polymerase, the microprocessor complex, transporter proteins, and Dicer, culminating in the production of mature miRNAs, which are then incorporated into AGO family proteins to form the RNA-induced silencing complex (RISC). This intricate machinery facilitates gene regulation by either cleaving target mRNA or inhibiting translation. miRNAs are integral to numerous biological processes, including intercellular communication, cell cycle control, immune responses, and host-microbe interactions. Furthermore, in recent years, the practical applications of miRNAs have rapidly expanded, encompassing disease diagnosis, therapeutic intervention, disease prognosis, enhancement of crop resilience to biotic and abiotic stress, environmental toxicology, drug development, cellular repair, and nutritional optimization. These research domains offer substantial promise for advancing our understanding of miRNA-mediated gene regulation and for developing innovative strategies to leverage their therapeutic and commercial potential.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102208"},"PeriodicalIF":1.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705590","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}
引用次数: 0
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