IUBMB Life最新文献

{"title":"Cellular Mechanisms and Therapeutic Targeting of Long Noncoding RNAs in Atherosclerotic Disease","authors":"Rasha Abu-Khudir,&nbsp;Ahmed S. Doghish,&nbsp;Mai A. Abd-Elmawla,&nbsp;Heba R. Ghaiad,&nbsp;Nora M. Aborehab,&nbsp;Mohamed Bakr Zaki,&nbsp;Hend H. Mohamed,&nbsp;Osama A. Mohammed,&nbsp;Rabab S. Hamad,&nbsp;Hanan Elimam","doi":"10.1002/iub.70090","DOIUrl":"10.1002/iub.70090","url":null,"abstract":"<div>\u0000 \u0000 <p>To effectively combat atherosclerotic diseases, it is essential to identify novel biomarkers and therapeutic targets that can detect early-stage atherosclerosis before the development of high-risk, unstable plaques. Due to their distinct chemical and biological characteristics, long noncoding RNAs (lncRNAs) have emerged as promising biomarkers for various diseases. This review highlights the potential therapeutic intervention targeting lncRNAs in atherosclerosis. Recent research has pointed out the significant role of lncRNAs in the pathogenesis and progression of atherosclerosis, influencing endothelial dysfunction in both proliferation and migration, lipid metabolism, and plaque stability through diverse molecular mechanisms such as NEAT1, lincRNA-p21, MALAT1, H19, GAS5, MEG3, HOTAIR, and TUG1. This study also emphasizes the role of lncRNAs in the diagnosis and prognosis of atherosclerosis, such as APPAT, MALAT1, MIAT, SOX2-OT, HIF1A-AS1, lncRNA-ATB, PVT1, NORAD, HOTAIR, H19, LIPCAR, and DANCR. The research highlighted the therapeutic intervention targeting various lncRNAs in atherosclerosis via different signaling pathways, such as TNF-<i>α</i>, JAK/STAT, IFN-<i>γ</i> signaling, ROCK1, AP1, and NF-κB signaling, PI3K/AKT/mTOR, which holds a new class of RNA-based therapeutics. The research aims to elucidate the crucial roles of lncRNAs in regulating gene expression and cellular processes involved in atherosclerosis development, which could emerge as potential therapeutic targets for atherosclerosis.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180024","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 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148061511","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":"ADAM15 Is a Potential Biomarker for Pan-Cancer Prognosis and Immunotherapy: Validation in HCC and COAD","authors":"Wenjia Guo,&nbsp;Yu’e Liu,&nbsp;Wencong Ma,&nbsp;Lieying Fan,&nbsp;Bingdi Chen,&nbsp;Jinghan Wang","doi":"10.1002/iub.70086","DOIUrl":"10.1002/iub.70086","url":null,"abstract":"<div>\u0000 \u0000 <p>A Disintegrin and metalloprotease (ADAM) family encompasses a diverse array of widely expressed proteases functioning in pathological processes. ADAM15 stands out as a pivotal mediator in multiple tumor types, responding to immune checkpoint inhibitors (ICI) significantly. By promoting pro-angiogenic genes, potentiating integrin binding as well as modulating the inflammatory response, ADAM15 orchestrates cellular adhesion and migration, thereby fostering tumor progression. Despite these compelling insights, the intricate roles of ADAM15 in prediction, immune modulation, and therapeutic targeting among malignant disorders remain largely unexplored. To decipher the pan-cancer landscape of ADAM15, we integrated data from multiple databases. Immunohistochemical profiles of ADAM15 were retrieved from the human protein atlas (HPA) database. Furthermore, the tumor immune estimation resource (TIMER) and the ESTIMATE (Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data) algorithm were harnessed to dissect the immune infiltration patterns and immune checkpoint genes associated with ADAM15. The tumor immune single-sample gene set enrichment analysis (TISMO) was employed to explore the impact of ADAM15 on the tumor immune microenvironment. Additionally, drug sensitivity analysis and subsequent molecular docking studies were conducted to identify potential therapeutic compounds targeting ADAM15. These findings were rigorously validated through reverse transcription-polymerase chain reaction (RT-PCR), western blotting (WB), and immunohistochemistry (IHC) by cell lines and clinical samples from hepatocellular carcinoma (HCC) as well as colon adenocarcinoma (COAD). Our comprehensive analysis revealed that ADAM15 is markedly upregulated in diverse cancer types. IHC, WB, and RT-PCR assays of HCC and COAD confirmed these findings. Notably, elevated ADAM15 correlates with adverse prognosis in pan-cancer, positioning it as a promising novel biomarker. Drug sensitivity profiling unveiled a positive and statistically significant association between ADAM15 and AZD-8055 and Nitazoxanide, whereas a negative correlation was observed with Oxaliplatin and Ponatinib. These findings were further corroborated by molecular docking simulations, highlighting the potential of these compounds as therapeutic targets for ADAM15-driven cancers. Our study underscores the multifaceted role of ADAM15 in cancer progression, immune evasion, and response to therapy. By elucidating the intricate interplay between ADAM15 and the tumor microenvironment (TME), we have identified novel diagnostic biomarkers and potential therapeutic avenues.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105480","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 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148061510","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 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148092430","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":"Punicalagin Targets FDX1 to Induce Cuproptosis for the Treatment of Gastric Cancer","authors":"Yuan-yuan Fang,&nbsp;Si-yi Zhang,&nbsp;Chuan-yu Leng,&nbsp; Jing-Lv,&nbsp;Shu-fen Zhao,&nbsp;Xue-ying Sun,&nbsp; Xin-Li,&nbsp;Yang-yang Lu,&nbsp; Bing-Wang,&nbsp;Wei-wei Qi","doi":"10.1002/iub.70088","DOIUrl":"10.1002/iub.70088","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;p&gt;Gastric cancer represents the fifth most common malignancy globally and the third leading cause of cancer-related deaths. Due to its insidious early symptoms and frequent metastasis at diagnosis, the survival rate remains dismal. There is thus an urgent clinical need for novel therapeutic agents. Innovative strategies combining traditional chemotherapy with interventions that induce novel cell death pathways represent a promising translational direction for improving patient outcomes. Punicalagin (PUN), a natural polyphenol derived from pomegranate, exhibits potent antioxidant and broad-spectrum antitumor activities, yet its role in gastric cancer remains understudied. Three gastric cancer cell lines (AGS, HGC27, MFC) and one normal gastric mucosal epithelial cell line (GES-1) were initially selected for in vitro experiments. The effects of PUN on gastric cancer cells and normal gastric mucosal epithelial cells were assessed through MTT assay, propidium iodide (PI) staining, and cell colony formation assays, while cell migration ability was evaluated using a scratch wound healing assay. The inhibitory effect of PUN on gastric cancer was tested in a subcutaneous tumor model in nude mice, with pathological changes in vital tissues and organs observed via hematoxylin and eosin (H&amp;E) staining. Subsequently, transcriptome sequencing was performed, and JC-1, H2DCFDA, and DHE staining methods were employed to measure mitochondrial function and reactive oxygen species (ROS) levels in PUN-treated cells. Western blotting was used to detect the expression of apoptosis- and cell cycle-related proteins. Next, two gastric cancer cell lines (AGS, HGC27) were selected for in vitro experiments to assess the combined effects of PUN and the copper ionophore elesclomol (ES) (hereafter referred to as ES-Cu, representing the combination of ES and Cu&lt;sup&gt;2+&lt;/sup&gt;). Cell viability was assessed using the MTT assay, and morphological changes were observed under a microscope. Cell proliferation and migration abilities were assessed via colony formation and scratch wound healing assays, respectively. Fluorescence staining was used to examine mitochondrial function and ROS levels in cells co-treated with PUN and ES-Cu. Laser confocal microscopy and Western blotting were employed to determine the oligomerization level of DLAT protein by quantifying soluble and insoluble protein expression, along with the expression of ACO2, ETFDH, FDX1, and LIAS proteins. Molecular docking, molecular dynamics simulations, immunofluorescence staining, and transfection techniques were utilized to confirm the critical role of FDX1 in copper-induced cell death following co-treatment with PUN and ES-Cu. We found that PUN could suppress the viability, proliferation, and migration of gastric cancer cells in a concentration- and time-dependent manner. Subsequent in vivo experiments demonstrated that PUN inhibited tumor growth in nude mice at a safe dosage. Besides, tra","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052303","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 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148084641","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":"Balancing Promise and Peril: Hemophilia Gene Therapy Insights","authors":"Saicharan Akula,&nbsp;Ester Borroni,&nbsp;Alessia Cottonaro,&nbsp;Antonia Follenzi,&nbsp;Simone Merlin","doi":"10.1002/iub.70087","DOIUrl":"10.1002/iub.70087","url":null,"abstract":"<p>Hemophilia is an inherited disorder characterized by impaired blood clotting caused by mutations in the genes responsible for producing coagulation factor (F) VIII (hemophilia A, HA) or FIX (hemophilia B, HB). Current treatment primarily relies on replacement therapy, involving frequent and costly infusions of FVIII or FIX concentrates. While effective, these treatments come with the risk of developing neutralizing antibodies (inhibitors) against the infused factor. In recent years, non-factor replacement therapies have emerged as innovative treatment options, offering enhanced efficacy especially for patients with inhibitors. Despite their advantages, these approaches still fall short of providing a definitive, long-term cure. Since hemophilia is a monogenic disease, it presents an excellent opportunity for cell and gene therapy approaches aimed at achieving durable treatment and potentially a cure. Over the past three decades, remarkable advancements have been made in hemophilia gene therapy, culminating in the approval of Valoctocogene roxaparvovec (ROCTAVIAN, AAV-FVIII) and Etranacogene dezaparvovec (HEMGENIX, AAV-FIX) for patients with severe HA and HB, respectively. Nevertheless, gene therapy poses questions regarding its long-term efficacy and safety. This review synthesizes findings from clinical trials, addresses persistent challenges in hemophilia gene therapy, and underscores the biological constraints and limitations inherent to viral vector-based approaches.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12813738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998214","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":"AdipoRon Suppresses Multiple Myeloma Proliferation Through AMPK-Mediated Metabolic Reprogramming and Apoptosis Induction","authors":"Zhaohui Wang,&nbsp;Xiaotian Su,&nbsp;Ruru Guo,&nbsp;Yanqiu Han,&nbsp;Jing Zhang","doi":"10.1002/iub.70084","DOIUrl":"10.1002/iub.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>Multiple myeloma (MM) remains an incurable hematologic malignancy, necessitating novel therapeutic strategies. This study investigates the clinical significance of adiponectin receptors and the anti-myeloma efficacy of their agonist, AdipoRon. Bioinformatic analysis of GEO datasets (GSE124489, GSE187009) revealed significant downregulation of ADIPOR1 and ADIPOR2 in MM patients. Low expression of ADIPOR1 correlated with poor prognosis. Functionally, AdipoRon exerted potent anti-proliferative effects on MM cell lines (U266, RPMI8226) in time- and dose-dependent manners. Mechanistic studies demonstrated that AdipoRon induced mitochondrial apoptosis, evidenced by increased cleavage of PARP and Caspase-9, and triggered G0/G1 cell cycle arrest. At the signaling level, AdipoRon activated the AMPK pathway while concurrently suppressing AKT phosphorylation. The critical role of AMPK was confirmed through pharmacological approaches: the AMPK activator AICAR mimicked AdipoRon's effects, whereas the AMPK inhibitor Compound C partially reversed them. Further investigation identified acetyl-CoA carboxylase (ACC) as a key downstream effector, with ACC inhibition (TOFA) recapitulating AdipoRon's anti-MM effects. Specifically, AdipoRon preferentially suppressed ACC1 expression and subsequently downregulated CPT1A, indicating disruption of fatty acid metabolism. These findings establish that AdipoRon suppresses MM progression through AMPK-driven metabolic reprogramming and apoptosis induction, positioning adiponectin receptor agonism as a promising therapeutic strategy for multiple myeloma.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917018","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":"Exosomal LncRNAs in Myocardial Ischemia: From Diagnostic Advantage to Therapeutic Targets","authors":"Mohammad Y. Alshahrani,&nbsp;Zahraa AlKhafaje,&nbsp;Uday Abdul-Reda Hussein,&nbsp;Zahraa Adel,&nbsp;Ola Kamal A. Alkadir,&nbsp;Ahmed Aldulaimi,&nbsp;Rafid Kamal Jameel,&nbsp;Rafid Jihad Albadr,&nbsp;Mariem Alwan,&nbsp;Aseel Smerat","doi":"10.1002/iub.70082","DOIUrl":"10.1002/iub.70082","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial ischemia (MI), which is a key form of ischemic heart disease, is still the most common cause of morbidity and mortality in the world. While reperfusion therapy has changed clinical management, many of the unmet needs for the early diagnosis and treatment of MI remain. Two rapid advances, namely, extracellular vesicle biology and the field of non-coding RNA genomics, have combined to identify a class of potent signaling molecules, exosomal long non-coding RNAs (lncRNAs). In this review, we characterize the specific functions of prominent exosomal lncRNAs in the core biological pathophysiological elements of MI, including apoptosis, inflammation, angiogenesis, autophagy, and fibrosis. Exosomal lncRNAs can either be involved in damaging – transmitting signals of injury—or restorative—driving repair and regeneration—and often play such roles based on their source and recipient. In addition to their therapeutic advantage, exosomal lncRNAs have enormous diagnostic capacity as stable, sensitive, and early-stage “liquid biopsy” diagnostics. By integrating core biology into clinical possibilities, we hope this review represents the field's current viewpoint and where it is heading to change the diagnosis and treatment of myocardial ischemia.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933385","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}