IUBMB Life最新文献

{"title":"MicroRNAs in HPV-Associated Carcinogenesis: Potential Biomarkers in Oropharyngeal and Cervical Cancers","authors":"Rabab S. Hamad,&nbsp;Ahmed S. Doghish,&nbsp;Sherif S. Abdel Mageed,&nbsp;Nehal I. Rizk,&nbsp;Osama A. Mohammed,&nbsp;Khaled M. Alam-Eldein,&nbsp;Khaled Abuelhaded,&nbsp;Haidy Adel Fahmy,&nbsp;Heba A. Saad,&nbsp;Gehad Elhadad,&nbsp;Asmaa M. Farahat,&nbsp;Reda M. Mansour","doi":"10.1002/iub.70117","DOIUrl":"10.1002/iub.70117","url":null,"abstract":"<div>\u0000 \u0000 <p>High-risk human papillomavirus (HPV) infection is a key etiological factor in cervical cancer (CC) and oropharyngeal squamous cell carcinoma (OPSCC). Increasing evidence indicates that host microRNAs (miRNAs) are central regulators in HPV-induced carcinogenesis and represent promising molecular biomarkers for diagnosis and prognosis. In cervical cancer, deregulated expressions of miRNAs such as miR-21, miR-27a, miR-34a, miR-155, and miR-218 have been consistently reported. These miRNAs influence critical pathways controlling apoptosis, cell proliferation, and immune evasion. The oncoproteins E6 and E7 from HPV can disrupt normal miRNA biogenesis, leading to the suppression of tumor-suppressor genes such as PTEN and PDCD4 and the activation of oncogenic signaling networks. Circulating miRNAs detected in serum and plasma, including miR-205 and miR-196a, show potential as non-invasive biomarkers for early detection and disease monitoring in cervical cancer (CC). In oropharyngeal cancer (OPC), particularly HPV-positive OPSCC, altered miRNAs such as miR-21, miR-31, miR-375, and miR-9 have been implicated in tumor initiation and progression. Distinct miRNA profiles have been observed between HPV-positive and HPV-negative tumors, suggesting a role for these molecules in differentiating subtypes with different clinical outcomes. Salivary and serum miRNA assays have shown potential for early detection, reflecting tumor-specific molecular changes in a minimally invasive manner. Overall, miRNA profiling offers a promising approach for stratifying HPV-associated cervical and OPCs. Integrating miRNA panels with HPV genotyping and epigenetic data may enhance precision in risk assessment and therapeutic targeting. Future longitudinal studies with standardized methodologies are needed to validate these miRNAs as reliable clinical biomarkers.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054584","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":"PGAM1 Orchestrates Cell Cycle Progression, Glycolytic Reprogramming, and Immunosuppressive Microenvironment in Triple-Negative Breast Cancer","authors":"Shunshun Zhang,&nbsp;Xuewei Zheng,&nbsp;Siya Tang,&nbsp;Yalin Zhang,&nbsp;Li Zeng,&nbsp;Jingjing Wang,&nbsp;Yanan Ouyang,&nbsp;Yanbin Du,&nbsp;Junxiang Wang,&nbsp;Youyou Chen,&nbsp;Yun Xue,&nbsp;Qinan Yin","doi":"10.1002/iub.70109","DOIUrl":"10.1002/iub.70109","url":null,"abstract":"<div>\u0000 \u0000 <p>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by uncontrolled cell cycle progression, profound metabolic reprogramming, and immune evasion, yet effective therapeutic targets remain limited. In this study, we integrated bulk and single-cell transcriptomic analyses to identify phosphoglycerate mutase 1 (PGAM1) as a central regulator of TNBC progression. Functional assays revealed that PGAM1 is significantly upregulated in TNBC tissues and cell lines, particularly associated with enhanced G2/M phase activity. Silencing PGAM1 suppressed TNBC cell proliferation and migration and induced cell cycle arrest at the G2/M phase. Mechanistically, PGAM1 knockdown impaired glycolytic flux by reducing the activity of rate-limiting enzymes, attenuating pyruvate entry into the TCA cycle, and consequently diminishing lactate production. Notably, this metabolic disruption extended beyond tumor-intrinsic effects: reduced lactate secretion inhibited M2-type tumor-associated macrophage polarization in co-culture systems, thereby alleviating immunosuppressive signaling in the tumor microenvironment. These findings highlight PGAM1 as a critical node linking three cancer hallmarks—cell cycle dysregulation, metabolic reprogramming, and immune evasion. By bridging intracellular metabolic control with immune modulation via lactate signaling, PGAM1 emerges as a promising therapeutic target that could simultaneously inhibit TNBC cell proliferation and remodel the tumor immune landscape.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042397","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":"Low SFXN1 Expression Predicts Poor Clinical Outcomes and Promotes Tumor Aggressiveness in Colon Adenocarcinoma","authors":"Jie Zhu,&nbsp;Yuchen Huang,&nbsp;Xiaoqin Wu,&nbsp;Liusuyu Zhu,&nbsp;Jiahao Liu,&nbsp;Jinhuan Wei,&nbsp;Xilin Sha","doi":"10.1002/iub.70107","DOIUrl":"10.1002/iub.70107","url":null,"abstract":"<div>\u0000 \u0000 <p>Sideroflexin 1 (SFXN1), predominantly localized in the inner mitochondrial membrane, exhibits differential expression across various tumor types. However, its specific role in colon adenocarcinoma (COAD) remains unclear. This study aimed to investigate the diagnostic and prognostic significance of SFXN1 in COAD. The expression and prognostic value of SFXN1 in COAD were evaluated using the Cancer Genome Atlas (TCGA) database. Bioinformatics analyses were conducted to assess the relationships between SFXN1 expression and clinical stage, prognosis, and immune infiltration in COAD. The biological role of SFXN1 in COAD was further validated through in vivo and in vitro experiments. SFXN1 was found to be expressed at low levels in COAD. Reduced SFXN1 expression was significantly associated with poor clinical outcomes in COAD patients. Furthermore, SFXN1 expression correlated with immune infiltration and immune checkpoint regulation in COAD. Functional experiments demonstrated that SFXN1 inhibition enhanced the proliferation, migration, and invasion of COAD cells, whereas SFXN1 overexpression suppressed tumor growth in vivo. Low SFXN1 expression is associated with an unfavorable clinical prognosis in COAD. Targeting SFXN1 may offer a promising avenue for developing personalized and more effective therapeutic strategies for patients with COAD.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815547","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":"Single-Cell Dissection of Malignant Cell Heterogeneity Reveals Functional Programs and Clinically Relevant Subtypes in Head and Neck Squamous Cell Carcinoma","authors":"Ahmed Osman Mohamed,&nbsp;Yin He,&nbsp;Xiaosheng Wang","doi":"10.1002/iub.70104","DOIUrl":"10.1002/iub.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis and limited predictive biomarkers for therapy response. Characterizing malignant cell heterogeneity may improve prognostic and therapeutic stratification. We integrated single-cell RNA sequencing (scRNA-seq) data from 58 HNSCC patients (181,003 cells) to define malignant cell subpopulations, their differentiation states, developmental trajectories, cell–cell interactions, and spatial localization. Coexpression gene modules and meta-programs were identified using hdWGCNA and NMF. These programs were projected onto bulk RNA-seq datasets to classify HNSCC subtypes and examine associations with clinical outcomes, tumor microenvironment (TME), genomic instability, and predicted response to immune checkpoint inhibitors (ICIs). Twelve malignant clusters were identified with distinct clinical and molecular features. MC-5 exhibited a stem-like phenotype associated with poor prognosis, while MC-7 and MC-11 showed high TME communication and immune engagement. Coexpression analysis revealed 16 modules and eight meta-programs encompassing proliferation, differentiation, stress response, and immune activity. Translation to bulk RNA-seq defined three HNSCC subtypes (MS-1, MS-2, MS-3) with divergent survival, immune infiltration, stromal composition, and genomic features. MS-2, an immune-enriched subtype, demonstrated superior survival, high HPV positivity, and predicted ICI responsiveness. A 25-gene malignant cell score (MCScore) robustly predicted both prognosis and immunotherapy response. This study provides a comprehensive map of malignant cell heterogeneity in HNSCC, identifies key functional expression programs, and defines molecular subtypes with clinical and therapeutic relevance. Malignant cell-specific signatures, such as MCScore, offer promising tools for patient stratification and precision immunotherapy.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815568","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":"Integration of Single-Cell and Spatial Transcriptomics With Experimental Validation Uncovers Macrophage Diversity and Spatial Landscape in Carotid Atherosclerosis","authors":"Rongxing Qin,&nbsp;Caiqi Li,&nbsp;Hongyu Xu,&nbsp;Xinyu Lai,&nbsp;Li Chen","doi":"10.1002/iub.70105","DOIUrl":"10.1002/iub.70105","url":null,"abstract":"<div>\u0000 \u0000 <p>The core pathogenesis of carotid atherosclerosis (CAS) lies in the rupture of vulnerable plaques, with macrophages (MC) playing a critical role in plaque progression and destabilization. However, the functional characteristics of MC subpopulations in CAS remain poorly understood. This study systematically investigates the cellular composition of CAS and the regulatory mechanisms of MC by integrating single-cell RNA sequencing (scRNA-seq), in vitro models, and spatial transcriptomics. Differentially expressed genes upregulated in MC were significantly enriched in multiple signaling pathways, including Lipid and Atherosclerosis, Lysosome, and Antigen Processing and Presentation. Gene Set Variation Analysis (GSVA) revealed higher MC scores for Angiogenesis and Lipid Metabolism in the atherosclerotic core (AC). A total of seven distinct MC subtypes were identified. Pseudotime analysis indicated that IGSF21+ MC constitute the initial cell population, while FABP4+ MC represent the terminal cells along the trajectory. An in vitro atherosclerosis model was established to validate the diagnostic value of <i>SPP1</i>, <i>FTH1</i>, and <i>FTL</i>. Spatial transcriptomics further revealed the spatial connection patterns of the SPP1 signaling pathway network across different cell types. This study provides novel molecular insights into the pathogenesis of CAS and lays the groundwork for developing diagnostic biomarkers and therapeutic targets.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771854","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":"HIF Signalling Modulates p53/miR-145-5p Axis in Hypoxia-Driven Tumorigenesis of HepG2 Tumourspheres","authors":"Sakunie Sawai,&nbsp;Pooi-Fong Wong,&nbsp;Thamil Selvee Ramasamy","doi":"10.1002/iub.70103","DOIUrl":"10.1002/iub.70103","url":null,"abstract":"<div>\u0000 \u0000 <p>Hypoxia is associated with increased tumour aggressiveness and relapses in hepatocellular carcinoma (HCC) through HIF signalling. Tumour suppressor p53, its deacetylase SIRT1 and liver-specific miRNAs are deregulated in hypoxia, further driving HCC tumorigenesis. The role of HIFs-p53-SIRT1-miRNAs in tumorigenesis of HepG2 tumourspheres under hypoxic conditions remains unexplored, hence is the focus of this study. HepG2 tumourspheres cultured under hypoxic and serum-free conditions for 19 days showed reduced proliferation and apoptosis, and increased pro-survival autophagy, CSC features and resistance. HIF-1α and HIF-2α proteins were stabilised in HepG2 tumourspheres cultured in hypoxia for up to 15 days compared to only up to 24 h in monolayer cells. p53 was activated in hypoxia, evidenced by significant increase in Ace-p53 expression and Ace-p53/total-p53 ratio, which were negatively correlated with HIF-1α/HIF-2α throughout hypoxia. Concurrently, nuclear p53 localisation was reduced in hypoxia, suggesting HIFs-suppression of p53 transcriptional activity. SIRT1 however, showed no correlation with p53 acetylation and HIF-1α/HIF-2α, with no notable changes in its nuclear-cytoplasmic localisation. Among the six selected miRNAs, miR-145-5p, -26a-5p and -375-3p were upregulated, miR-22-3p was downregulated, while miR-29c-3p and miR-34a-5p remained unchanged. miR-145-5p showed a negative correlation with p53 expression in hypoxia. Pharmacological inhibition of HIFs resulted in significant upregulation of p53 and miR-375-3p, while SIRT1, miR-145-5p and miR-26a-5p were downregulated. miR-145-5p was negatively correlated with p53 protein when HIFs were stabilised but positively correlated when HIFs were inhibited. This study highlights the role of HIFs/p53/miR-145-5p-associated regulation under hypoxic conditions in HepG2 tumourspheres, providing insights for future therapeutic exploration in HCC.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771907","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148087832","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":"Hypoxia-Inducible Factors as Guardians of Cancer Stem Cell Fate: Implications for Novel Therapies","authors":"Qamar Abuhassan,&nbsp;Hamzeh J. Al-Ameer,&nbsp;Hani Moslem Ahmed,&nbsp;Jasur Rizaev,&nbsp;Azizbek Togaev,&nbsp;Rasim M. Salih,&nbsp;Mohaned Adil","doi":"10.1002/iub.70092","DOIUrl":"10.1002/iub.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer stem cells (CSCs) represent a dynamic, therapy-refractory subpopulation that fuels tumor initiation, metastasis, and relapse through remarkable self-renewal capacity and phenotypic plasticity. Extensive evidence has established that hypoxia-inducible factors (HIFs), especially HIF-1α and HIF-2α, are key regulators of CSC behavior within the hypoxic tumor microenvironment (TME) across diverse malignancies, including breast cancer, glioblastoma, and colorectal carcinoma. Under hypoxic conditions, HIFs stabilization orchestrates stemness maintenance, epithelial-mesenchymal transition (EMT), immune evasion, and metabolic reprogramming. Concurrently, HIF activity upregulates efflux transporters and anti-apoptotic genes, thereby contributing to resistance against chemotherapy and radiotherapy. This review integrates recent advances in HIF-CSC crosstalk, with particular emphasis on interactions with core pluripotency networks (Oct4, Sox2, Nanog), therapy-induced CSC enrichment, and hypoxia-driven immune suppression. We further highlight current limitations and prospects of HIF-targeted strategies, including isoform-specific inhibitors and combination regimens. By addressing existing knowledge gaps, this work provides a comprehensive framework to guide the development of next-generation therapies aimed at durable CSC eradication and improved clinical outcomes in hypoxia-driven cancers.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722785","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148084751","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":"Nanocurcumin in Oral Disease Therapy: A Review of Innovations and Future Prospects","authors":"Quanbing Wang,&nbsp;Ke Jiang,&nbsp;Xiaofei Lan,&nbsp;Lan Zhang,&nbsp;Yuyan Duan,&nbsp;Jinxing Gao,&nbsp;Hong Chen","doi":"10.1002/iub.70099","DOIUrl":"10.1002/iub.70099","url":null,"abstract":"<div>\u0000 \u0000 <p>Curcumin exhibits strong anti-inflammatory, antioxidant, and anticancer activities. However, its clinical use is limited due to poor solubility, low gastrointestinal absorption, and rapid systemic metabolism. Nanocurcumin offers enhanced solubility, bioavailability, and targeted delivery through systems such as nanoparticles, liposomes, micelles, and nanoemulsions. In oral health, nanocurcumin has shown significant therapeutic promise. In periodontitis models, it attenuates pro-inflammatory cytokines and oxidative stress markers. In radiation- and chemotherapy-induced oral mucositis, randomized clinical trials report reduced lesion severity and pain scores with nanomicellar curcumin compared to placebo. Studies on oral lichen planus and aphthous ulcers have demonstrated superior symptom control and lesion resolution with nanocurcumin compared to conventional curcumin or corticosteroids. Preclinical data in oral squamous cell carcinoma reveal antiproliferative, pro-apoptotic, and anti-angiogenic effects mediated through the NF-κB, STAT3, and MAPK pathways. This review explores nanoformulation strategies, their physicochemical advantages, and therapeutic outcomes across in vitro, in vivo, and clinical studies. It also addresses translational challenges like stability, cost, and regulatory hurdles and discusses future perspectives including personalized nanomedicine and multifunctional nanocarriers. Nanocurcumin represents a promising advancement in oral therapeutics with potential to bridge current gaps in treatment efficacy and drug delivery.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698685","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}