Gene最新文献

{"title":"The role of the NEAT1/miR410-3p axis in the invasion of breast cancer cells","authors":"Cihangir Dogan,&nbsp;Ibrahim Acikbas,&nbsp;Buket Er Urganci,&nbsp;Zahra Azizi","doi":"10.1016/j.gene.2025.149379","DOIUrl":"10.1016/j.gene.2025.149379","url":null,"abstract":"<div><div>Breast cancer, which is the most common cancer among women in Türkiye and throughout the world, is also one of the leading causes of cancer-related deaths. A significant factor in these deaths is metastatic breast cancer, which spreads to distant organs. The metastasis of the breast tumor follows a series of steps. Many proteins and signal molecules are in charge of these processes. In addition, NEAT1, a long noncoding RNA (lncRNA), was reported to play a key role in breast cancer cell proliferation and survival. Numerous cancer kinds were also shown to have extraordinary miR-410-3p expression levels. NEAT1 and miR-410-3p expression patterns in MCF-7 and MCF-10A cell lines were investigated using quantitative real-time polymerase chain reaction (qRT-PCR) in this study. The results demonstrated that NEAT1 was elevated by 2.30-fold in cancer cells in comparison to normal cells, whereas miR-410-3p was diminished by −2.85-fold. Furthermore, the transwell invasion experiment demonstrated the invasive potential of the MCF-7 cell line, whereas the MCF-10A cells could not invade. The target analysis revealed that functions of the targets were associated with biological adhesion and cel growth. In conclusion, a correlation was found between overexpression of NEAT1 and increased invasiveness of target cells, as well as inhibition of miR-410-3p, which is a regulatory target of NEAT1.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"951 ","pages":"Article 149379"},"PeriodicalIF":2.6,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556485","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 nature and pathological impact of the c.1748A > G variant of the neurofibromin 1 gene","authors":"Ji-young Lee ,&nbsp;Eun Sook Kim ,&nbsp;Su Yeon Kim ,&nbsp;Yun-jung Cho ,&nbsp;Kwan Hoon Jo ,&nbsp;Je Ho Han ,&nbsp;Sung-dae Moon","doi":"10.1016/j.gene.2025.149381","DOIUrl":"10.1016/j.gene.2025.149381","url":null,"abstract":"<div><div>Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, and mutations in the <em>NF1</em> gene lead to RAS overactivation, which stimulates abnormal cell proliferation and can cause various tumors. The c.1748A &gt; G mutation in the <em>NF1</em> gene was initially classified as a missense mutation, but has also been suggested to be a splice mutation. It is thought that the substitution of A for G generates a cryptic splice site, resulting in a 27 bp deletion in the mRNA transcript, but this conclusion has not been documented in currently available databases. The present study was conducted to establish whether the <em>NF1</em> c.1748A &gt; G mutation induces a splicing error, and to determine whether it is pathogenic i.e. activates RAS and increases the expression of NF1-related downstream signaling molecules. We have confirmed by RT-PCR analysis of NF1 transcripts produced in the patient’s peripheral blood lymphocytes as well as in a minigene construct and in iPSCs harboring the c.1748A &gt; G mutation that this mutation creates a cryptic splice site which has the effect of deleting the first 27 bases of exon 16, and leading to transcriptional haploinsufficiency. Additionally, NPCs expressing the splicing mutant exhibited increased phosphorylation of NF1-related AKT/mTOR and Raf/MEK/Erk, as well as more effective wound healing and chemotaxis. We conclude that the <em>NF1</em> c.1748A &gt; G mutation acts as a splice mutation forming a novel cryptic site, causing a 27 bp deletion in the mRNA. This leads to increased expression of NF1-related downstream signaling molecules through RAS activation, inducing cell proliferation and potential tumor formation.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"952 ","pages":"Article 149381"},"PeriodicalIF":2.6,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556483","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":"miRNA-1229-5p promotes migration and invasion and suppresses apoptosis of endometrial cells via the STMN1/p38 MAPK axis in endometriosis","authors":"Lusha Liu ,&nbsp;Lixian Wang ,&nbsp;Na Hao ,&nbsp;Naiyi Du ,&nbsp;Yan Li ,&nbsp;Shan Kang","doi":"10.1016/j.gene.2025.149385","DOIUrl":"10.1016/j.gene.2025.149385","url":null,"abstract":"<div><h3>Background</h3><div>Emerging evidence suggests that aberrantly expressed microRNAs (miRNAs) participate in endometriosis pathogenesis. miR-1229-5p participates in the pathogenesis of several disease, but its precise role and mechanism in endometriosis is unclear.</div></div><div><h3>Methods</h3><div>Endometrial tissues were obtained from patients with endometriosis and healthy controls. RT-qPCR and western blotting were employed to detect the expression levels of genes and proteins, respectively. Transcriptome sequencing and luciferase reporter assay were utilized to identify the target of miR-1229-5p. CCK-8, transwell assay, wound healing assay and flow cytometry assay were performed to evaluate the functional roles of miR-1229-5p. Finally, the clinical significance of miR-1229-5p was furtherly analyzed.</div></div><div><h3>Results</h3><div>MiR-1229-5p was upregulated in ectopic endometrium of ovarian endometriosis patients (n = 60) compared to normal endometria of controls (n = 40), and its expression also served as an indicator for endometriosis severity. STMN1 was identified as the target of miR-1229-5p by luciferase experiments, and its expression was significantly downregulated in ectopic endometrium. Functionally, miR-1229-5p overexpression promoted migration, invasion, and inhibited apoptosis of ESCs and Ishikawa cells. Meanwhile, upregulation of miR-1229-5p also facilitated the protein expression of Bcl-2, MMP2, MMP9, N-cadherin, and ZEB1, and repressed the protein levels of Bax and E-cadherin. Whereas downregulation of miR-1229-5p exerted opposite effects. Importantly, STMN1 overexpression could partially reverse the effects of miR-1229-5p upregulation. Mechanistically, miR-1229-5p activates the p38 mitogen-activated protein kinase (p38 MAPK) signaling via targeting STMN1.</div></div><div><h3>Conclusion</h3><div>The newly identified miR-1229-5p-STMN1-p38 MAPK axis illustrates the molecular mechanism of endometriosis progression and offers a potential therapeutic target for treating endometriosis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"950 ","pages":"Article 149385"},"PeriodicalIF":2.6,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535267","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":"Heritable Genetic Variability in Ovarian Tumours: Exploring Venous Thromboembolism Susceptibility and Cancer Prognosis in a Hospital-Based Study","authors":"Valéria Tavares ,&nbsp;Joana Savva-Bordalo ,&nbsp;Mariana Rei ,&nbsp;Joana Liz-Pimenta ,&nbsp;Joana Assis ,&nbsp;Deolinda Pereira ,&nbsp;Rui Medeiros","doi":"10.1016/j.gene.2025.149378","DOIUrl":"10.1016/j.gene.2025.149378","url":null,"abstract":"<div><div>Venous thromboembolism (VTE) is a frequently encountered paraneoplastic syndrome in patients with ovarian cancer (OC), an inflamm-aging entity. VTE is known to exacerbate their already poor prognosis, which is partially attributed to the contribution of the haemostatic system to ovarian tumourigenesis. In the past decade, numerous single-nucleotide polymorphisms (SNPs) implicated in VTE pathways have been proposed to influence tumour susceptibility and progression. These SNPs represent potential tools to improve the prognosis accuracy of OC patients. Hence, this study explored the influence of 12 haemostasis-associated SNPs on the risk for VTE, risk of OC progression and related death among 98 OC patients. The findings revealed a 20.5 % incidence of VTE, which was associated with more rapid disease progression and shorter survival times (log-rank test, <em>p</em> &lt; 0.05). <em>PROCR</em> rs10747514 (AA/AG vs. GG; odds ratio (OR) = 3.67, <em>p</em> = 0.037) and <em>SERPINE1</em> rs2070682 (CC/CT vs. TT; OR = 9.28, <em>p</em> = 0.040) were predictors of OC-related VTE development. Regarding patients’ prognosis regardless of venous thrombogenesis, <em>RGS7</em> rs2502448, <em>F3</em> rs1361600, <em>FGG</em> rs2066865, and <em>SERPINE1</em> rs2070682 were the most relevant biomarkers in different patient groups. These genetic variants might constitute attractive prognostic indicators among OC patients, offering insights to refine disease management strategies. However, due to the small cohort size and the study’s retrospective nature, external validation is necessary to assess the generalisation of the findings.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"950 ","pages":"Article 149378"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540909","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":"Proteomic profiling of kars knockout zebrafish larvae","authors":"Jingjing Wang ,&nbsp;Xiao Yu ,&nbsp;Ying Wang ,&nbsp;Shiyuan Li ,&nbsp;Wenxin Shen ,&nbsp;Zhuang Jiang ,&nbsp;Jiping Wang","doi":"10.1016/j.gene.2025.149377","DOIUrl":"10.1016/j.gene.2025.149377","url":null,"abstract":"<div><h3>Background</h3><div><em>KARS</em> encodes both mitochondrial and cytoplasmic lysyl-tRNA synthetase, which is one of the aminoacyl-tRNA synthetases (ARSs) necessary for protein translation. Pathogenic variants in <em>KARS</em> have been reported to be involved in hearing loss, visual disorders, neuropathology, and diseases combined with multisystem phenotypes. <em>In vitro</em> studies have shown that <em>KARS</em> mutations cause a decrease in aminoacylation. However, the pathogenetic mechanisms underlying the complex neurological phenotypes remain largely unknown.</div></div><div><h3>Methods</h3><div>We developed <em>kars</em> knockout zebrafish and proteomic analyses on larvae with different genotypes at five days post-fertilization were performed using isobaric tags for relative and absolute quantitation (iTRAQ). Then the differentially abundant proteins (DAPs) analyzed by iTRAQ were validated by parallel reaction monitoring (PRM).</div></div><div><h3>Results</h3><div>420 differentially abundant proteins were identified between the knockout and wildtype groups, of which, 138 were up-regulated and 282 down-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses showed the greatest DAP cluster enrichment in ribosome (<em>P</em> = 2.1 × 10^-6, 28 genes), aminoacyl-tRNA biosynthesis (<em>P</em> = 7.34 × 10^-6, 13 genes), and hypertrophic cardiomyopathy (<em>P</em> = 7.45 × 10^-6, 28 genes). A further PRM-based analysis identified changes in <em>nars</em>, <em>mybphb</em>, <em>atp2a1l</em>, <em>col6a1</em> and <em>rps3a</em> that were specially linked to <em>kars</em>-deficency.</div></div><div><h3>Conclusions</h3><div>This work provides new valuable <em>in vivo</em> data for understanding the molecular mechanism of <em>KARS</em> deficiency-associated diseases, and will give us comprehensive insights into ARS-related disorders.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"950 ","pages":"Article 149377"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540914","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":"Glucose transporter-1 (GLUT-1) upregulation in vitiligo: A possible link to skin depigmentation","authors":"Amira A.M. Emam ,&nbsp;Moustafa M.K. Eyada ,&nbsp;Amal H.A. Gomaa ,&nbsp;Noha M. Abd El-Fadeal ,&nbsp;Gehan H. Ibrahim ,&nbsp;Mohamed K. El-Kherbetawy ,&nbsp;Noha Z. Tawfik","doi":"10.1016/j.gene.2025.149383","DOIUrl":"10.1016/j.gene.2025.149383","url":null,"abstract":"<div><h3>Background</h3><div>Vitiligo is a prevalent autoimmune skin disorder characterized by progressive depigmented patches of the skin and/or mucosa. Lately, extensive research has been investigating molecular pathogenesis underlying vitiligo, epidermal-immune cell crosstalk, structural aberrations in cellular skin components and immune cell metabolism derangements. Glucose transporter-1 (<em>GLUT-1</em>) has recently proved to be increased in proinflammatory conditions and autoimmune diseases. <em>GLUT-1</em> expression is upregulated in rheumatoid arthritis, systemic lupus erythematosus, psoriasis and chronic spongiotic dermatitis.</div></div><div><h3>Objective</h3><div>To investigate <em>GLUT-1</em> expression in vitiligo.</div></div><div><h3>Subjects and methods</h3><div>The study included 30 vitiligo patients “vitiligo vulgaris” and 30 healthy individuals. Biopsies of the patients’ lesional vitiligo skin and the control group’s normal skin were obtained. They were all tested for <em>GLUT-1</em> mRNA expression using real-time polymerase chain reaction (RT-PCR) and <em>GLUT-1</em> antibody expression using immunohistochemistry (IHC). Hematoxylin and eosin (H&amp;E) staining for the specimens was additionally done for histopathological assessment.</div></div><div><h3>Results</h3><div><em>GLUT-1</em> expression was upregulated in lesional skin of vitiligo patients compared to normal control skin (<em>P</em>-value &lt; 0.001). Also, lesional specimens from stable disease showed more <em>GLUT-1</em> expression than active disease but without a significant difference (<em>P</em>-value = 0.283). There was no significant correlation between the proposed vitiligo histological scoring system and vitiligo signs of the disease activity score.</div></div><div><h3>Conclusion</h3><div><em>GLUT-1</em> could play a crucial role in vitiligo disease onset, persistence and progression, through keratinocyte-melanocyte-fibroblast-immune cell crosstalk, being the initially deranged metabolic pathway for all these cells giving an insight into vitiligo metabolomics.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"950 ","pages":"Article 149383"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540960","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":"Analysis of ferroptosis-related key genes and regulatory networks in diabetic foot ulcers","authors":"Jianxiong Qiao ,&nbsp;Hanghang Zhou ,&nbsp;Jiale Wang ,&nbsp;Juan Wang ,&nbsp;Lin Zhong ,&nbsp;Jianguo Chen ,&nbsp;Xuanfen Zhang","doi":"10.1016/j.gene.2025.149375","DOIUrl":"10.1016/j.gene.2025.149375","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Diabetic foot ulcers (DFUs) is a severe complication of diabetes. Recent evidence suggests that ferroptosis, a form of regulated necrosis, may play a significant role in the progression of DFU. However, the precise molecular mechanisms remain elusive.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study aims to identify ferroptosis-related genes (FRGs) and the signaling pathways involved in DFU progression by analyzing the gene expression profiles of DFU.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Differentially expressed genes (DEGs) were identified by analyzing gene expression data from two DFU-related datasets (GSE38396, and GSE143735). FRGs were collected from both datasets and the literature. DEGs were then intersected with FRGs to identify ferroptosis-related differentially expressed genes (FRDEGs) in DFU. Functional enrichment analysis, protein–protein interaction (PPI) network analysis, receiver operating characteristic (ROC) curve analysis, and regulatory network interaction analysis (including mRNA-miRNA, mRNA-transcription factor (TF), and mRNA-drug interactions) were performed on the FRDEGs. Additionally, immune infiltration analysis was conducted using CIBERSORTx. Finally, skin tissue samples from clinical patients were collected, and the expression levels of FRDEGs in DFU samples were validated through reverse transcription quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC) and Immunofluorescence (IF), to uncover potential new targets for the diagnosis and treatment of DFU.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 14 DFUs samples (non-healing group) and 12 control samples (healing group) were obtained in this study. We identified 276 DEGs in DFUs samples compared to controls, with 121 up-regulated and 155 down-regulated genes. By intersecting DEGs with ferroptosis-related genes, we identified 10 FRDEGs (AURKA, CTH, FBLN1, FTL, GLS2, KDM5C, MYH9, PCNA, PYCR1, and SPARC). The GO and KEGG analysis results showed that FRDEGs were mainly enriched in biological processes such as amino acid biosynthesis and tight junction pathways. Further analysis of FRDEGs identified ten hub genes closely associated with 112 TFs, 34 miRNAs, and 50 drugs or molecular compounds. Additionally, RT-qPCR validation of skin tissue samples from 8 DFU patients and 8 controls showed that AURKA were significantly up-regulated in DFU, IHC and IF analysis further demonstrated elevated AURKA protein expression in DFU samples. Moreover, AURKA was identified as a potential diagnostic marker for diabetic wound healing, with high diagnostic accuracy based on ROC curve analysis (AUC = 0.950 in the combined dataset, and AUC = 0.881 in the validation dataset). These findings highlight AURKA as a key gene involved in ferroptosis and a potential target for the diagnosis and monitoring of DFUs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study identified FRDEGs associated with DFUs, highlighting AURKA as a key diagnostic marker. These f","PeriodicalId":12499,"journal":{"name":"Gene","volume":"950 ","pages":"Article 149375"},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537059","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":"Exploring the dual role of SIVA1 in cancer biology","authors":"Natália Sudan Parducci,&nbsp;Anali Del Milagro Bernabe Garnique,&nbsp;Bruna Oliveira de Almeida,&nbsp;João Agostinho Machado-Neto","doi":"10.1016/j.gene.2025.149365","DOIUrl":"10.1016/j.gene.2025.149365","url":null,"abstract":"<div><div>The intricate molecular mechanisms associated with cancer development continue to engage researchers due to the significant impact of the disease on global mortality. This review delves into the role of the apoptosis regulatory protein SIVA1, which has emerged as a significant player in cellular homeostasis. SIVA1, initially characterized as a pro-apoptotic protein interacting with the TNF receptor CD27, has since been implicated in various cellular contexts, revealing its complex functional dynamics. The <em>SIVA1</em> gene, located on chromosome 14, encodes a protein containing distinctive structural features, including an amphipathic helix and a death domain homology region. Localization studies show that SIVA1 is present in both the cytoplasm and nucleus, with its expression linked to tumor differentiation. Investigations into SIVA1′s interactions have uncovered its pro-apoptotic mechanisms, such as binding to anti-apoptotic proteins from the BCL2 family, thus promoting apoptosis under stress conditions. Interestingly, SIVA1 also exhibits tumor-promoting properties in specific cancer types, suggesting a dual role in apoptosis induction and tumor progression. As research progresses, understanding the regulatory mechanisms governing SIVA1′s multifaceted functions could pave the way for novel therapeutic strategies aimed at manipulating its activity for improved cancer treatment outcomes. Future studies are warranted to clarify SIVA1′s contextual roles and explore its potential clinical implications.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"950 ","pages":"Article 149365"},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535266","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":"GALR1 and PENK serve as potential biomarkers in invasive non-functional pituitary neuroendocrine tumours","authors":"Zerui Wu ,&nbsp;Changjun Rao ,&nbsp;Yilin Xie ,&nbsp;Zhen Ye ,&nbsp;Yichao Zhang ,&nbsp;Zengyi Ma ,&nbsp;Zhipeng Su ,&nbsp;Zhao Ye","doi":"10.1016/j.gene.2025.149374","DOIUrl":"10.1016/j.gene.2025.149374","url":null,"abstract":"<div><h3>Background</h3><div>Some nonfunctioning pituitary neuroendocrine tumor (NFPitNET) can show invasive growth, which increases the difficulty of surgery and indicates a poor prognosis. However, the molecular mechanism related to invasiveness remains to be further studied. This study is to screen and identify the characteristic biomarkers of invasive NFPitNETs.</div></div><div><h3>Methods</h3><div>Based on the data of 73 NFPitNETs microarray chips in the GSE169498 dataset, this study used weighted gene co-expression network (WGCNA), differential expression analysis, protein–protein interaction (PPI) network analysis and various machine learning methods (XGBOOST, LASSO regression, random forest, support vector machine) to screen candidate biomarkers for invasive NFPitNET. Then, using gene set enrichment analysis (GSEA) to explore the differences in biological activities and signaling pathways between invasive NFPitNET and non-invasive NFPitNET. Single-sample GSEA (ssGSEA) was used to analyze key biomarkers-related signaling pathways. Finally, the expression and function of the key biomarkers were verified by q-RT PCR, immunohistochemical (IHC) experiments and in vitro experiments.</div></div><div><h3>Results</h3><div>Combined with WGCNA and differential expression analysis, 128 high-expression and 85 low-expression candidate biomarkers were preliminarily obtained. PPI analysis and four machine learning algorithms further identified GALR1, PENK and HOXD9. The receiver operating characteristic (ROC) curve results showed that the three biomarkers had good predictive ability of invasiveness. After combining the validation set data, GALR1 and PENK were the final key biomarkers. Finally, PCR and IHC results verified the decreased expression of GALR1 and PENK in invasive NFPitNET and promotes proliferation and invasive ablity of pituitary tumor cells.</div></div><div><h3>Conclusion</h3><div>This study confirmed that the reduced expression of GALR1 and PENK is an important molecular feature of invasive NFPitNETs, which may play an important role in inhibiting the development of NFPitNET.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"950 ","pages":"Article 149374"},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537061","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":"Corrigendum to “PWWP2A/B: Prominent players in the proteomic landscape” [Gene 942 (2025) 149245]","authors":"Saravanaraman Ponne ,&nbsp;Raj Kumar Chinnadurai ,&nbsp;Rajender Kumar ,&nbsp;Aman Kumar Mohanty ,&nbsp;Raimunda Sâmia Nogueira Brilhante ,&nbsp;Trinh Thi Trang Nhung ,&nbsp;Sudhakar Baluchamy","doi":"10.1016/j.gene.2025.149344","DOIUrl":"10.1016/j.gene.2025.149344","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"948 ","pages":"Article 149344"},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537060","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}