Critical Reviews in Eukaryotic Gene Expression最新文献

{"title":"Identification and Validation of a Novel Prognostic Signature of Gastric Cancer Based on Seven Complement System-Related Genes: An Integrated Analysis.","authors":"Jiaxing Zhang, Weijing Zhu, Shengrui Yang, Jie Liu, Futian Tang, Yumin Li","doi":"10.1615/CritRevEukaryotGeneExpr.2024057000","DOIUrl":"10.1615/CritRevEukaryotGeneExpr.2024057000","url":null,"abstract":"<p><p>The complement system (CS) is linked to the progression of gastric cancer (GC), which has a high mortality rate, though its mechanisms in GC remain unclear. This study aims to identify CS-related prognostic genes with causal links to GC, and to investigate their mechanisms. The intersection between differentially expressed genes (DEGs) obtained from the TCGA-STAD dataset and CS-related genes (CRGs) was defined as differentially expressed CRGs (DCRGs). Prognostic genes with a causal association with GC (pCDCRGs) were sequentially identified via Mendelian randomization (MR) analysis and Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, followed by expression analysis. A gene signature and a nomogram were then established based on pCDCRGs and independent prognostic factors. Subsequent analyses focused on functional enrichment, immune relevance, drug sensitivity, gene interactions, and molecular regulatory networks. Eventually, reverse transcription-quantitative PCR (RT-qPCR) was employed to validate expression of pCDCRGs. DCRGs were obtained from the intersection of 8,418 DEGs and 241 CRGs. Among 12 DCRGs with causal association (CDCRGs) with GC, 7 genes were identified as pCDCRGs, including FANCG, FANCF, F2R, C4BPA, SERPINF2, PROC, and CD59. Notably, CD59 was markedly highly expressed in the normal group, whereas the other genes were markedly highly expressed in the GC group. Afterward, an accurate pCDCRG signature was developed. Risk score, age, and stage were recognized as independent risk factors, and the constructed nomogram demonstrated strong predictive accuracy. Additionally, analyses indicated that these 7 pCDCRGs may influence GC by affecting pathways such as complement and coagulation cascades, immune cell infiltration, immune characteristics, immunotherapy responses, and drug sensitivity. These effects may be linked to gene interactions and the regulatory roles of lncRNAs like RMRP and miRNAs such as hsa-mir-613. RT-qPCR showed C4BPA, PROC, F2R, and SERPINF2 were markedly up-regulated, whereas CD59 was markedly down-regulated in GC tissues. This study identified seven complement system-related prognostic genes with causal links to GC, based on which we developed a highly predictive 7-pCDCRG signature, providing valuable insights for clinical prognostic prediction and immunotherapy in GC patients.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 3","pages":"1-22"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of T Cell-Related Hub Biomarkers for Early Diagnosis of Diabetic Kidney Disease Using Single-Cell and Bulk Dataset Analysis.","authors":"Zhenhua Wu, Meifang Ren, Miao Tan, Bing Yang, Suzhi Chen, Fengwen Yang, Guodong Yuan, Jinchuan Tan","doi":"10.1615/CritRevEukaryotGeneExpr.2025056960","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2025056960","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is the most common complication of diabetes and a leading cause of chronic kidney disease that frequently leads to end-stage renal disease (ESRD). The pathogenesis of DKD is complex and is not fully understood. This study was designed to identify key targets for DKD diagnosis and explore the underlying molecular mechanisms.</p><p><strong>Methods: </strong>DKD-specific clusters were selected from single-cell datasets. Gene modules were identified using hairpin-dynamic weighted gene co-expression network analysis (hdWGCNA). Multiple machine learning algorithms were applied to model and screen hub genes from two bulk datasets. Rat model of DKD was built using optical microscopes to observe the histopathological changes in the kidney by HE, PAS, and Masson staining. The expression of RASGRP3, PDE3B, and CD247 in DKD-Rat was verified by RT-PCR, and the expression of RASGRP3, PDE3B, and CD247 in the serum samples of DKD patients was verified by ELISA. The results of sex and age, RASGRP3, PDE3B, CD247 were calculated by multivariate logistic regression analysis.</p><p><strong>Results: </strong>Three hub genes were obtained through screening single-cell and two bulk datasets. In-depth exploration of the potential molecular mechanisms of the hub genes was conducted using gene set variation analysis (GSVA), immune infiltration analysis, and single-cell correlation analysis. Receiver operating characteristic (ROC) curve confirmed a high diagnostic value of the hub biomarkers, and a high-efficiency diagnostic model was constructed and mutually validated in the two datasets. We found that damaged tubular number and interstitial fibrotic percentage were significantly increased in DKD rat. As shown by HE, PAS and Masson staining, the mRNA levels of PDE3B and CD247 were markedly upregulated in DKD rat compared with those in the control group. Lower expression levels of RASGRP3 mRNA were manifested in DKD. The levels of RASGRP3, PDE3B, CD247 in DKD patients by ELISA were statistically significant (p < 0.05). PDE3B and CD247 had an AUC value greater than 0.9,RASGRP3 had an AUC value greater than 0.7.</p><p><strong>Conclusion: </strong>This study identified 3 T cell-related hub biomarkers, providing references for the early diagnosis of DKD and changes in T cells during DKD progression.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 4","pages":"65-84"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specific Non-Coding RNAs Involve in and Regulate the Transcriptional Network during Keloid Formation.","authors":"Xun Zhang, Linlin Song, Yong Ma, Zifu Zhou, Qiyun Luo, Juan Zhang, Yaozhu Yang, Lei Liu, Lifeng Guan","doi":"10.1615/CritRevEukaryotGeneExpr.2025056805","DOIUrl":"10.1615/CritRevEukaryotGeneExpr.2025056805","url":null,"abstract":"<p><p>Keloid formation is an undesirable outcome of wound healing and is detrimental to patients' physical and mental health, while the molecular regulators of its pathogenesis, especially non-coding RNAs (ncRNAs), are largely unknown. In this study, we integrated and analyzed RNA-seq and miRNA microarray datasets of skin samples from keloid-prone and healthy normal individuals to detect the dysregulated long ncRNAs (lncRNAs) and miRNAs. We excavated 583 and 104 keloid-specific lncRNAs and miRNAs, respectively. Moreover, the molecular functions of these ln-cRNAs and miRNAs are all related to ossification. Next, we constructed the relationship between lncRNAs and immune cell infiltration, and found the macrophages, NK cells, and dendritic cells were specifically dysregulated in keloid-prone or normal groups during wound healing. We constructed the potential regulatory network between these cell types and 20 dysregulated lncRNAs, suggesting their regulatory function in keloid formation. At last, we constructed the competitive endogenous RNA network and found two hub lncRNAs and five miRNAs, including DLEU1 and SLC25A21-AS1, miR-197-5p, miR-940, miR-6765-5p, miR-711, and miR-4284, which were highly dysregulated during keloid formation. In summary, these results demonstrate that lncRNAs and miRNAs play important roles and form a regulatory network in the pathogenesis, immune infiltration, and development of keloid formation.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 3","pages":"63-74"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Network Macromolecules.","authors":"George L Eliceiri","doi":"10.1615/CritRevEukaryotGeneExpr.2025055921","DOIUrl":"10.1615/CritRevEukaryotGeneExpr.2025055921","url":null,"abstract":"<p><p>The members of the network (interactome) that controls cancer needs to be known. This network consists of proteins and non-coding, single-stranded RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and transfer RNAs (tRNAs). miRNAs are 21-23 nucleotides-long, and degrade messenger RNAs (mRNAs) and lncRNAs. lncRNAs are longer than 200 nucleotides, and sponge (sequester) miRNAs.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 3","pages":"75-84"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and gene analysis in 7 Chinese children with cystic fibrosis.","authors":"Chunyan Guo, Xing Chen, Fengqin Liu, Yan Liang, Juan Yang, Fangfang Dai, Ning Ding, Ke Wang, Jing Zhang","doi":"10.1615/CritRevEukaryotGeneExpr.2025057731","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2025057731","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) is common genetic disorder in Europe and North America but rarer in Asian populations.</p><p><strong>Objective: </strong>To explore the clinical manifestations and gene mutations of cystic fibrosis.</p><p><strong>Methods: </strong>This case series study enrolled children with CF diagnosed in the pediatric respiratory department of Shandong Provincial Hospital affiliated to Shandong First Medical University between June 2016 and August 2022.</p><p><strong>Results: </strong>Seven children, including 6 girls and 1 boy, were enrolled. All 7 patients had recurrent wet cough and (chronic) pneumonia. Six patients suffered from chronic sinusitis, 4 patients had recurrent wheezing; 2 patients had chronic diarrhea, malnutrition and growth lag; 2 patients were complicated by allergic bronchopulmonary aspergillosis; and 1 patient had pancreatic insufficiency. Bronchiectasis, thickening of bronchial wall and mucous impaction, were seen in the chest CT of 7 children. Six patients showed a large amount of viscous sputum adhered to the bronchial wall by bronchoscopy. Infection of Pseudomonas aeruginosa was found in 6 cases, Staphylococcus aureus in 2 cases, and Aspergillus fumigatus in 2 cases by bronchoalveolar lavage fluid or sputum culture. Sweat sodium chloride test was performed in 3 cases, and the result showed that Cl-> 60 mmol/L. CFTR gene mutations were found in 7 cases, which were rare mutations of Caucasians, including 2 cases with new mutation sites (c.325T>G and 326A>G).</p><p><strong>Conclusions: </strong>The major clinical presentations of CF could be chronic and recurrent upper and lower respiratory tract infections, malnutrition, and digestive tract diseases. The rare and even new mutations of Caucasians on CFTR gene may occur in Chinese children.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 4","pages":"55-64"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircCNKSR2 Facilitates NSCLC Tumorigenesis and Warburg Effect via miRNA-138-5p/PLEK2 Axis.","authors":"Dongxiao Ding, Ke Shi, Junjie Ying, Wenjun Shang, Chengli Du","doi":"10.1615/CritRevEukaryotGeneExpr.2024055827","DOIUrl":"10.1615/CritRevEukaryotGeneExpr.2024055827","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) has a high global incidence and mortality rate. Although circRNAs have significant attention in tumor research, it's role in NSCLC is uncertain. QRT-PCR and Western blotting were utilized to quantify the expression of circCNKSR2, miR-138-5p, and PLEK2 in NSCLC tissues and cells. The characteristics and subcellular localization of circCNKSR2 were determined using RNase R analysis and qRT-PCR. In vitro functional experiments determined the biological functions of circCNKSR2. The specific binding interactions among circCNKSR2, miR-138-5p, and PLEK2 were evaluated through bioinformatics analysis, luciferase reporter, and rescue assays. In vivo xenograft model was established to examine the impact of circCNKSR2, which was significantly increased in NSCLC tissues and cells. Functional studies demonstrated that silencing circCNKSR2 significantly inhibited NSCLC malignant phenotype and Warburg effect. Bioinformatics analysis and rescue experiments verification indicated circCNKSR2 functioned as a miR-138-5p sponge, and inhibiting miR-138-5p reversed the suppressive effect of silencing circCNKSR2 in NSCLC. Additionally, PLEK2 identified as a miR-138-5p target gene. The potential regulatory role of circCNKSR2 in NSCLC progression and Warburg effect via the miR-138-5p/PLEK2 pathway was demonstrated.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 2","pages":"49-63"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HECW1 Gene's Role in Gastric Cancer Prognosis and Its Suppressive Effect on Cell Progression after Knockdown.","authors":"Jinchuan Wang, Baozhen Wang, Yichen Yin, Nan Tian, Tao Li","doi":"10.1615/CritRevEukaryotGeneExpr.2025058112","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2025058112","url":null,"abstract":"<p><strong>Background: </strong>The HECT, C2, and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) gene is a member of the HECT family of E3 ubiquitin ligases. While HECW1 has been implicated in various cancers, its role in gastric cancer (GC) remains unclear.</p><p><strong>Methods: </strong>Bioinformatics approaches were employed to investigate HECW1's role in GC. Functional assays, including the CCK-8, transwell migration, and wound healing assays, were performed to assess its impact on GC cell proliferation, invasion, and migration.</p><p><strong>Results: </strong>HECW1 expression was significantly upregulated in GC tissues compared to normal controls, correlating with specific clinical characteristics. Cox regression analyses identified HECW1 as an independent prognostic factor for GC. Prognostic nomograms accurately predicted 1-, 3-, and 5-year survival rates, with calibration curves closely aligned with the ideal diagonal line. Elevated HECW1 expression was associated with poorer overall survival and disease progression outcomes. ROC analyses demonstrated that HECW1 had strong predictive power for outcomes (AUC = 0.746, CI = 0.683-0.808) and five-year survival rates (AUC = 0.734, CI = 0.600-0.869). Enrichment analysis suggested HECW1's involvement in protein processing and interactions with substrates such as SMAD4, TTF1, DVL1, and NEDD4. Functional assays showed that HECW1 knockdown significantly reduced GC cell proliferation, invasion, and migration.</p><p><strong>Conclusions: </strong>HECW1 acts as an oncogene in GC and represents a potential prognostic indicator. Targeting HECW1 may inhibit GC progression, providing a promising therapeutic strategy.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 5","pages":"1-16"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL16-Mediated Upregulation of FGD5-AS1 Promotes Progression of Osteosarcoma through Targeting of miR-195-5p/SLC7A2 Axis.","authors":"Weiqian Wu, Wenbiao Zheng, Weiwei Pan, Fanghu Chen, Langqing Jiang","doi":"10.1615/CritRevEukaryotGeneExpr.2025058118","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2025058118","url":null,"abstract":"<p><p>Dysregulated long noncoding RNAs (lncRNAs) promote the progression of osteosarcoma (OS). This study aimed to investigate the potential of lncRNA FGD5-AS1 in OS. Gene expression was determined using RT-qPCR. Protein expression was detected by western blot. N6-methyladenosine (m6A) modification was confirmed by MeRIP. Cell behaviors were detected using CCK-8, colony formation, and transwell assays. The interaction between miR-195-5p and the FGD5-AS1/SLC7A2 axis was confirmed by luciferase assays. FGD5-AS1 was upregulated in OS, induced by METTL16 via mediating m6A modification. However, FGD5-AS1 knockdown inhibited the proliferation and epithelial-mesenchymal transition (EMT) of OS cells. FGD5-AS1 sponged miR-195-5p to mediate the upregulation of SLC7A2, overexpression of which promoted aggressiveness of OS cells. In summary, METTL16-mediated upregulation of FGD5-AS1 promotes the aggressiveness of OS though targeting of miR-195-5p/SLC7A2 axis.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 5","pages":"17-31"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AKT Signals by Infrared Light in Cancer.","authors":"Ziv Radisavljevic","doi":"10.1615/CritRevEukaryotGeneExpr.2025059075","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2025059075","url":null,"abstract":"<p><p>Cancer cells are a complex and robust system dynamically interconnected by the signaling genes network through the up-regulated AKT gene. How signals are transmitted still is not clear. The hyperphosphorylated AKT locus during protein-protein interaction sends infrared (IR) light as a signal to the other molecules and cells for cancer proliferation, migration, and angiogenesis. The hyperactivated AKT locus in cancer transmits IR light with a wavelength different from that in normal cells that is mechanistically characteristic of AKT-mediated control of cancer, recommended for targeting therapy by IR resonance. Thus, signaling is achieved by IR light. Such signaling is the first response of the hyperactivated AKT gene, far ahead of any biochemical response, activating the interactome network and creating a robust cancer system.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 5","pages":"53-58"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multispectral Imaging of Intrinsic Metabolic Fluorophores: Detection of Human Breast Cancer in Fresh Ex Vivo Specimens.","authors":"Gary E Carver, Mark D Entwistle, Prachi N Ghule, Kyra C Lee, Donald L Weaver, Michelle M Sowden, Seth P Harlow, Jessica A Cintolo-Gonzalez, Janet L Stein, Gary S Stein","doi":"10.1615/CritRevEukaryotGeneExpr.2025057627","DOIUrl":"10.1615/CritRevEukaryotGeneExpr.2025057627","url":null,"abstract":"<p><p>A growing number of women develop breast cancer and require surgery. Many lumpectomies lead to follow-up procedures after the initial surgery. Advanced scanning technologies have reduced the number of second and third surgeries, but only by about 50%. This paper assesses the potential of using multispectral images of intrinsic fluorescence to detect breast cancer. Images and spectra of intrinsic fluorescence from fresh ex vivo human specimens are related to pathological analysis, and predict high sensitivity and specificity. A design for a hand-held surgical scanning tool is presented.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"35 3","pages":"43-50"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}