Biochimica et biophysica acta. Molecular basis of disease最新文献

{"title":"Hydroxysafflor yellow A inhibits neuronal ferroptosis and ferritinophagy in ischemic stroke","authors":"Yige Wu ,&nbsp;Lijun Yin ,&nbsp;Zeqian Wang ,&nbsp;Shuwen Yuan ,&nbsp;Dong Ma ,&nbsp;Chunli Wen ,&nbsp;Hao Tian ,&nbsp;Baoguo Xiao ,&nbsp;Cungen Ma ,&nbsp;Lijuan Song","doi":"10.1016/j.bbadis.2025.167867","DOIUrl":"10.1016/j.bbadis.2025.167867","url":null,"abstract":"<div><div>Ischemic stroke is a significant cause of disability and mortality on a global scale, with neuronal dysfunction playing a critical role in its pathogenesis. Conventional treatment approaches for ischemic stroke involve surgical interventions and thrombolytic therapy, yet these methods frequently result in ischemia/reperfusion (I/R) injury. Recent studies have underscored the implication of diverse programmed cell death mechanisms, including ferroptosis, in the progression of ischemic stroke. Ferroptosis, a newly recognized form of cell death reliant on iron, is intricately linked to various neurological conditions. Despite the existing body of research on ferritinophagy and neuronal ferroptosis in the context of cerebral ischemia-reperfusion injury, there is a lack of understanding regarding the mechanisms involved in neuronal ferroptosis. This study seeks to explore the relationship between neuronal autophagy and neuronal ferroptosis using in vivo and in vitro models of cerebral ischemia/reperfusion. The findings of our study reveal a significant upregulation of the ferritinophagy-associated protein NCOA4 following cerebral ischemia/reperfusion, concomitant with the initiation of ferroptosis in neuronal cells. This observation offers compelling support for a direct association between neuronal ferritinophagy and ferroptosis. Hydroxysafflor Yellow A (HSYA), a traditional Chinese herb, shows promise in reducing brain ischemia/reperfusion injury, but its exact protective mechanism is still unknown. Our study reveals a new way HSYA protects the brain by preventing neuronal ferroptosis after a stroke, a mechanism not previously reported.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167867"},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of DRD5P2 in hypoxia attenuates Rock2 degradation to promote EMT and gastric cancer metastasis","authors":"Zhenjia Yu ,&nbsp;Tao Pan ,&nbsp;Xiaofeng Wang ,&nbsp;Zhijian Jin ,&nbsp;Yifan Lu ,&nbsp;Xiongyan Wu ,&nbsp;Junyi Hou ,&nbsp;Airong Wu ,&nbsp;Zhen Li ,&nbsp;Xinyu Chang ,&nbsp;Quan Zhou ,&nbsp;Jianfang Li ,&nbsp;Wentao Liu ,&nbsp;Zhentian Ni ,&nbsp;Zhongyin Yang ,&nbsp;Chen Li ,&nbsp;Min Yan ,&nbsp;Bingya Liu ,&nbsp;Chao Yan ,&nbsp;Zhenggang Zhu ,&nbsp;Liping Su","doi":"10.1016/j.bbadis.2025.167858","DOIUrl":"10.1016/j.bbadis.2025.167858","url":null,"abstract":"<div><h3>Background</h3><div>Metastasis is the leading cause of gastric cancer (GC)-related death. However, the molecular mechanisms underlying GC metastasis are not well understood. In this study, we focused on dopamine receptor 5 pseudogene 2 (DRD5P2), a novel long non-coding RNA, in GC metastasis.</div></div><div><h3>Methods</h3><div>Expression of DRD5P2 in GC was detected by real-time PCR (RT-PCR) and fluorescence in situ hybridization (FISH). The effect of DRD5P2 in GC cells was examined by transwell invasion and migration assays. The pathways underlying DRD5P2/Rock2 signaling were studied by Western blot, co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP) and RNA immunoprecipitation (RIP) analysis. Regulatory mechanism between hypoxia and DRD5P2 expression was explored in vitro by ChIP and Dual-luciferase reporter assays.</div></div><div><h3>Results</h3><div>DRD5P2 expression is downregulated in advanced human GC and is associated with poor clinical outcomes. Gain- and loss-of-function studies showed that DRD5P2 inhibits GC cell migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, as well as peritoneal dissemination in vivo. Mechanistic analysis revealed that DRD5P2 binds with Rock2 and recruits the E3 ubiquitin ligase KAP1 to mediate Rock2 degradation, thus suppressing the Ezrin/HRAS/ERK/CREB pathway and ultimately attenuating Snail-mediated EMT and GC metastasis. Furthermore, DRD5P2 transcription is inhibited by hypoxia in a HIF-1α/ZNF263-dependent manner in GC cells.</div></div><div><h3>Conclusions</h3><div>DRD5P2 acts as a tumor suppressor in GC metastasis by suppressing Rock2/ERK/Snail signaling, and DRD5P2 is transcriptionally suppressed under hypoxia via the HIF-1α/ZNF263 axis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167858"},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GDF15 drives de novo lipogenesis and contributes to ovarian cancer metastasis","authors":"Chenxi Wang ,&nbsp;Zhengjie Ou ,&nbsp;Hongming Deng ,&nbsp;Ying Zhang ,&nbsp;Xiaoyang Li ,&nbsp;Xiaobing Wang ,&nbsp;Dan Zhao","doi":"10.1016/j.bbadis.2025.167868","DOIUrl":"10.1016/j.bbadis.2025.167868","url":null,"abstract":"<div><div>Ovarian cancer is frequently diagnosed at an advanced stage, characterized by extensive metastasis. Recent studies indicate that metastatic and primary tumors exhibit similar mutational landscape, suggesting that non-mutational factors significantly contribute to the metastatic process. Enhanced lipid metabolism has been implicated across various stages of cancer progression, making the targeting of metabolic vulnerabilities a promising therapeutic strategy. In this study, we demonstrate that growth differentiation factor 15 (GDF15), a member of the TGF-β superfamily, which has been Indicated to be associated with several metabolic diseases, is significantly elevated in the serum of ovarian cancer patients, particularly in metastatic lesions compared to primary tumors. Elevated GDF15 levels correlate with reduced overall survival and progression-free survival. Furthermore, we found that GDF15 facilitates tumor metastasis by regulating de novo lipogenesis through the PI3K/AKT signaling pathway. These findings suggest that targeting GDF15-mediated lipid metabolism could provide a novel therapeutic approach to inhibit ovarian cancer metastasis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167868"},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variant-specific disruption to notch signalling in PAX6 microphthalmia and aniridia patient-derived hiPSC optic cup-like organoids","authors":"Philippa Harding ,&nbsp;Nicholas Owen ,&nbsp;Jonathan Eintracht ,&nbsp;Dulce Lima Cunha ,&nbsp;Brian Chan ,&nbsp;Joe Rainger ,&nbsp;Mariya Moosajee","doi":"10.1016/j.bbadis.2025.167869","DOIUrl":"10.1016/j.bbadis.2025.167869","url":null,"abstract":"<div><div>The homeobox-containing transcription factor PAX6 is a key regulator of eye development. Pathogenic heterozygous <em>PAX6</em> variants lead to variable ocular phenotypes, most commonly haploinsufficiency-induced aniridia. Missense variants are typically associated with milder ocular conditions, although variants in the DNA-binding paired domain which alter target binding lead to severe ocular phenotypes including bilateral microphthalmia, similar to <em>SOX2</em>-anophthalmia syndrome. However, the variant-specific pathway disruption resulting in phenotypic heterogeneity is not well understood. To investigate pathogenic mechanisms of <em>PAX6</em> variants, transcriptomic and chromatin accessibility analysis was performed on hiPSC derived 3D optic cup-like organoids generated from patients with variants (i) PAX6^N124K displaying combined microphthalmia, aniridia and optic nerve coloboma, and (ii) PAX6^R261X exhibiting typical aniridia. Total RNA sequencing analysis revealed downregulation of <em>SOX2</em> in missense PAX6^N124K cups compared to both wildtype and PAX6^R261X haploinsufficient aniridia controls, along with Notch signalling components and markers of proliferation and differentiation. Transcription factor binding motifs of Notch-related genes were also found to be differentially bound in PAX6^N124K cups through ATACseq footprinting analysis. Our analysis of <em>PAX6</em>-related oculopathies using in vitro models reveals disruption to DNA binding perturbs <em>SOX2</em> and Notch signalling, contributing to severe ocular phenotypes in patients with missense changes in the paired domain. This work reveals a previously unestablished role for PAX6 in SOX2 and Notch signalling regulation during early oculogenesis, as well as illuminating disease mechanisms underlying variant-specific ocular phenotypes and genotype-phenotype correlations. These novel insights can influence clinical care, and provide valuable data on potential therapeutic targets, which can guide future translational research.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167869"},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of ALDH2 accelerates the progression of pulmonary arterial hypertension through the 4-HNE/ERK1/2-p16INK4a signaling pathway","authors":"Zhengyu Sun ,&nbsp;Wendi Jiang ,&nbsp;Guoqing Lu ,&nbsp;Yangyang Ding ,&nbsp;Lei Wang ,&nbsp;Jiayi Geng ,&nbsp;Ningning Zhang ,&nbsp;Hongju Wang ,&nbsp;Pinfang Kang ,&nbsp;Bi Tang","doi":"10.1016/j.bbadis.2025.167863","DOIUrl":"10.1016/j.bbadis.2025.167863","url":null,"abstract":"<div><div>Senescence is an important causative factor in the development of pulmonary arterial hypertension (PAH). Aldehyde dehydrogenase 2 (ALDH2), an enzyme involved in aldehyde detoxification, plays a role in cardiovascular diseases associated with aldehyde accumulation. This study aimed to investigate the role of ALDH2 in hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs) and PAH. ALDH2 knockout (ALDH2^−/−) mice and wild-type (WT) mice were exposed to a hypoxic environment with 10 ± 0.5 % oxygen concentration for 4 weeks to develop a chronic hypoxia-induced PAH (HPH) mouse model. We found that right ventricular hypertrophy and pulmonary arteriole muscularization were more severe in ALDH2^−/− mice compared to WT mice. Additionally, ALDH2^−/− mice exhibited elevated expression levels of 4-HNE, p-ERK1/2, the senescence-related protein p16^INK4a, and the senescence-associated secretory phenotype (SASP) compared to WT mice. Similarly, treatment with the ALDH2 inhibitor (Daidzin) significantly increased 4-HNE, p-ERK1/2, p16^INK4a, and SASP levels in PASMCs under hypoxia. Conversely, overexpression of ALDH2 reduced 4-HNE, p-ERK1/2, and PASMC senescence. Furthermore, exogenous 4-HNE, used to simulate hypoxia conditions, activated the ERK signaling pathway and induced PASMC senescence. However, ERK-specific inhibitors (PD98059) blocked hypoxia-induced PASMC senescence. These results demonstrate that ALDH2 deficiency induces PASMC senescence and promotes pulmonary vascular remodeling through the 4-HNE/ERK1/2-p16^INK4a signaling pathway in HPH, providing a novel target for PAH treatment.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167863"},"PeriodicalIF":4.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-10 alleviates aTCMR by inhibiting NFATc1 signaling pathway of T cells after kidney transplantation","authors":"Sheng-Li Liu ,&nbsp;Peng Zhao ,&nbsp;Yan-Man Zhou ,&nbsp;Zhi-Guo Peng ,&nbsp;Ning Guo ,&nbsp;Huai-Bin Sun ,&nbsp;Xian-Quan Cui","doi":"10.1016/j.bbadis.2025.167857","DOIUrl":"10.1016/j.bbadis.2025.167857","url":null,"abstract":"<div><div>The cause of acute T cell-mediated rejection (aTCMR) is believed to be immune hyperfunction of T cells after kidney transplantation. Nowadays, calcineurin inhibitors are widely used to inhibit the proliferation of T cells when aTCMR occurs. However, the therapeutic dose window of these drugs is relatively narrow and long time use of these drugs may lead to serious side effects. Besides, whether IL-10, a new immune tolerance mediator, playing a therapeutic role on aTCMR remains unclear. The level of IL-10 decreased in patients with aTCMR, suggesting that IL-10 may be involved in the progression of aTCMR. IL-10 could inhibit the proliferation and metabolism of T cells in vitro and in vivo, accompanied by reducing the levels of IL-2, IFN-γ, and TNF-α. Moreover, we confirmed that IL-10 exerts immunosuppressive effects by inhibiting the NFATc1 signaling pathway of T cells. This viewpoint may provide a new therapeutic idea for clinical application.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167857"},"PeriodicalIF":4.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling heart failure by induced pluripotent stem cell-derived organoids.","authors":"Irene Bissoli ,&nbsp;Francesco Alabiso ,&nbsp;Cristina Cosentino ,&nbsp;Aleksandra Seragnoli Chystyakova ,&nbsp;Fabrizio Ferré ,&nbsp;Francesco Alviano ,&nbsp;Pasquale Marrazzo ,&nbsp;Carla Pignatti ,&nbsp;Giulio Agnetti ,&nbsp;Romano Regazzi ,&nbsp;Flavio Flamigni ,&nbsp;Stefania D’Adamo ,&nbsp;Silvia Cetrullo","doi":"10.1016/j.bbadis.2025.167861","DOIUrl":"10.1016/j.bbadis.2025.167861","url":null,"abstract":"<div><div>Cardiac organoids offer significant advantages for in vitro studies, as their 3D structure and cellular composition more closely replicate tissue complexity compared to 2D models. This is particularly relevant for studying complex diseases like heart failure (HF), which involve multiple cell types and cardiac structures. Thus, the primary aim of this study was to produce self-assembled, scaffold-free cardiac organoids from induced pluripotent stem cells (iPSCs), capable of simulating key aspects of HF in vitro. Gene expression analysis confirmed a transition from stemness markers (OCT4, NANOG) to cardiac markers (TNNT2, DES), validating their cardiac phenotype. To induce hallmark HF features, endothelin-1 (ET-1) treatment was applied.</div><div>Key findings indicate that this experimental model successfully reproduced HF pathological markers, including the upregulation of genes encoding atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and the cytoskeletal protein α-skeletal actin (ACTA1), along with changes in microRNA (miR) expression profiles. Functionally, ET-1 treatment reduced organoid contractility, indicating a decline in contractile function—a hallmark of HF. Furthermore, histological analyses by Thioflavin T (ThT) staining, ThT fluorescence assay and filter trap assay on protein extracts demonstrated protein aggregation following ET-1 treatment. Co-administration of various nutraceuticals was shown to mitigate these effects. These findings underscore the value of this ET-1-stimulated cardiac organoid model as a powerful platform for studying HF mechanisms and evaluating novel therapeutic approaches.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167861"},"PeriodicalIF":4.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The improvement in diagnostic yield of developmental and epileptic encephalopathy by the multi-omics sequential testing method","authors":"Shuang-Hao Yang ,&nbsp;Jiatong Liu ,&nbsp;Yuan Quan ,&nbsp;Guangyu Lin ,&nbsp;Xiaohua Zhou ,&nbsp;Hua He ,&nbsp;Xianfeng Gan ,&nbsp;Tuanfeng Yang ,&nbsp;Ming-Yang Cui ,&nbsp;Xilong Du ,&nbsp;Xiaofang Quan ,&nbsp;Weiyue Gu ,&nbsp;Hong-Yu Zhang ,&nbsp;Hua Wang ,&nbsp;WenZheng Guan","doi":"10.1016/j.bbadis.2025.167854","DOIUrl":"10.1016/j.bbadis.2025.167854","url":null,"abstract":"<div><div>Despite traditional panel and Whole Exome Sequencing (WES) assays, the causative factors for 60 % of epilepsy cases remain elusive, mainly due to incomplete detection of variant spectrums, and limited ability to interpret variants. Our research developed the multi-omics method of a comprehensive sequential testing methodology, to enhance the diagnostic yield for the etiology. In this study, we performed sequential multi-omics analyses on a cohort of 236 Chinese patients exhibiting recurrent seizures along with developmental delay or intellectual disability. Our study had devised a comprehensive multi-omics variant analysis methodology in a sequential mode. The initial analytical strategy included WES, CNV-seq and in-house cases evidence. If no pathogenic cause was identified, the subsequent analytical approach in the sequential mode included the analysis of WGS SVs, mitochondrial variations, dynamic mutations, and abnormalities in RNA-seq. Our results revealed that the initial step achieved a diagnostic detection rate of 44.1 % (104 cases). Subsequently, WGS and RNA-seq testing were performed, with 33 familial diagnoses tested positive, representing a 14 % increase. Meanwhile our pipeline has elucidated the pathogenicity classification of 72 variants which are either not yet recorded in the ClinVar database or are classified as VUS. Our study achieved an overall positive diagnostic rate of 58.1 % (137/236). In summary, our pipeline can detect comprehensive variant spectrums and provide a clear interpretation of variations with unclear clinical significance, the multi-omics sequential testing approach significantly improves the rate of genetic diagnosis for epileptic disorders.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167854"},"PeriodicalIF":4.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson's disease and gut microbiota metabolites: The dual impact of vitamins and functional amyloids","authors":"Fatemeh Mirab ,&nbsp;Mitra Pirhaghi ,&nbsp;Daniel E. Otzen ,&nbsp;Ali Akbar Saboury","doi":"10.1016/j.bbadis.2025.167862","DOIUrl":"10.1016/j.bbadis.2025.167862","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurodegenerative disorder characterized by the abnormal accumulation of alpha-synuclein (α-Syn). Recent research emphasizes the significant role of the gut microbiota, the diverse community of microbes living in the intestines, in modulating α-Syn pathology. This review explores the bi-directional communication along the microbiota-gut-brain axis, highlighting the paradoxical impact of two gut microbiota metabolites—functional bacterial amyloids (FuBA) and vitamins—on neurodegenerative diseases, particularly PD. FuBA contributes to PD pathogenesis by promoting α-Syn aggregation, while vitamins offer neuroprotection through their anti-amyloidogenic, antioxidant, and anti-inflammatory properties. Understanding these processes could lead to precision clinical approaches and novel strategies for managing and preventing PD.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167862"},"PeriodicalIF":4.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant protein glycosylation in the colon adenoma-cancer sequence: Colorectal cancer mechanisms and clinical implications","authors":"He Yingli ,&nbsp;Yang Ping ,&nbsp;Yan Jun ,&nbsp;Zhu Xingwang","doi":"10.1016/j.bbadis.2025.167853","DOIUrl":"10.1016/j.bbadis.2025.167853","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a leading contributor to global cancer-related morbidity and mortality. Glycosylation is a common post-translational protein modification. Aberrant protein glycosylation is a hallmark of cancer, affecting biological processes and driving malignant CRC phenotypes. Specifically, abnormal N-glycosylation manifests as structural alterations in high mannose, sialylated, and fucosylated structures, collectively promoting cancer stemness and invasiveness. Concurrently, O-GlcNAcylation facilitates tumorigenesis through metabolic reprogramming and oncogene activation. Dysregulated mucin-type O-glycans (e.g., Core-1/Core-3 imbalance) and elevated SLex/SLea antigen expression are significantly correlated with tumor adhesion, metastatic dissemination, and adverse clinical outcomes. Furthermore, protein glycosylation contributes to chemoresistance through anti-apoptotic mechanisms, aberrant signaling activation, and pro-angiogenic pathways. This review systematically examines the dynamic evolution of protein glycosylation during CRC progression from normal mucosa to adenoma to adenocarcinoma. It also evaluates the CRC diagnostic and therapeutic implications of glycoproteins and glycans. This review can provide a molecular understanding for advancing CRC diagnostics and treatment.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167853"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}