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

{"title":"SREBP1a induced PINK1-Parkin mediated mitophagy facilitates ovarian cancer progression","authors":"Sk. Eashayan Tanbir ,&nbsp;Sib Sankar Roy","doi":"10.1016/j.bbadis.2025.168043","DOIUrl":"10.1016/j.bbadis.2025.168043","url":null,"abstract":"<div><div>Sterol regulatory element binding protein 1 (SREBP1) has emerged as a central regulator of lipid metabolism, playing a pivotal role in cancer progression. However, the oncogenic potential of SREBP1a is still underexplored. This study investigates the multifaceted contributions of SREBP1a on tumorigenesis, with a particular focus on ovarian cancer. Elevated expression of the SREBP1a isoform was found to enhance proliferation, migration, and invasion of ovarian cancer cells. Mechanistically, SREBP1a induces mitochondrial fission by upregulating DRP1 expression and promoting its activation through ser616 phosphorylation, resulting in a fragmented mitochondrial network that supports enhanced bioenergetic flexibility. In parallel, SREBP1a drives PINK1-Parkin-mediated mitophagy. This coupling of mitochondrial fission and mitophagy possibly ensures mitochondrial quality control, enhances cellular bioenergetics, and increases ATP production, supporting rapid cell proliferation and migration. Experimental evidences reveal that SREBP1 directly regulates DRP1 and PINK1 transcription, reinforcing its role in regulating mitochondrial dynamics. Furthermore, targeting SREBP1 using Fatostatin, a small-molecule inhibitor, effectively disrupts mitochondrial fission, impairs mitophagy, and attenuates tumor progression. These findings highlight the novel role of SREBP1a as a key regulator of mitochondrial dynamics, establishing it as a promising therapeutic target in ovarian cancer. Future studies should explore combinatorial strategies integrating SREBP1a inhibition with existing therapies to improve treatment outcomes.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168043"},"PeriodicalIF":4.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061222","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":"Single-cell multi-omics reveals SLC2A1-driven glycolytic reprogramming of pulmonary endothelial cells in sepsis-associated lung injury","authors":"Dingde Long ,&nbsp;Ziyun Lu ,&nbsp;Bei Fang ,&nbsp;Ying Tian ,&nbsp;Huan Fu ,&nbsp;Yang Dong ,&nbsp;Tianyuan Li","doi":"10.1016/j.bbadis.2025.168050","DOIUrl":"10.1016/j.bbadis.2025.168050","url":null,"abstract":"<div><div>Sepsis-induced lung injury is driven by pathological remodeling of pulmonary microvascular endothelial cells (PMVECs), yet the metabolic underpinnings of endothelial dysfunction remain poorly understood. Using single-cell multi-omics analysis of PMVECs from septic patients, we identified profound metabolic reprogramming dominated by glycolysis upregulation, orchestrated through the HIF-1/PI3K-Akt signaling axis. Integrated bioinformatics (Seurat/WGCNA) and experimental validation in a murine sepsis model revealed that SLC2A1-mediated glycolytic flux sustains PMVEC dysfunction, exacerbating tissue inflammation, apoptosis, and fibrosis. Targeted inhibition of glycolysis via SLC2A1 siRNA attenuated metabolic stress, evidenced by reduced extracellular acidification rate (Seahorse) and tricarboxylic acid cycle suppression (metabolomics), while restoring endothelial proliferation, migration, and VEGF/HIF1A homeostasis. Mechanistically, glycolytic inhibition decreased leukocyte infiltration (IHC) and alveolar damage, correlating with improved lung repair metrics. This study establishes PMVEC glycolysis as a keystone of sepsis-associated acute lung injury (ALI), where metabolic reprogramming transitions from adaptive survival signaling to maladaptive tissue injury. Our findings highlight SLC2A1-driven glycolytic pathways as actionable targets for mitigating endothelial dysfunction and advancing metabolic intervention strategies in septic ALI.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168050"},"PeriodicalIF":4.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066736","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":"Multi-omics integrative analysis elucidates the molecular characteristics of SMARCA4-deficient lung adenocarcinoma and the derived therapeutic options","authors":"Deyu Guo ,&nbsp;Kai Wang ,&nbsp;Shijie Sun ,&nbsp;Yuxiang Chi ,&nbsp;Jiajun Du ,&nbsp;Wei Dong","doi":"10.1016/j.bbadis.2025.168051","DOIUrl":"10.1016/j.bbadis.2025.168051","url":null,"abstract":"<div><div>SMARCA4-deficient lung adenocarcinoma (LUAD) is highly aggressive with multiple oncogene mutations, and has low sensitivity to chemotherapy, targeted therapy and immunotherapy. By integrating multi-omics analysis and machine learning analysis on 20 lung adenocarcinoma datasets, we characterized SMARCA4 mutation in clinical prognosis, metabolic level, immune infiltration and pathway enrichment. The key role of SMARCA4 in LUAD development was confirmed by several <em>in vitro</em> and <em>in vivo</em> experiments. SMARCA4 is highly expressed in LUAD tissues compared with adjacent tissues, and SMARCA4 mutation is a poor prognostic factor. Although SMARCA4-deficient LUAD patients are not sensitive to common chemotherapeutic drugs, immunotherapy is an alternative treatment for lung adenocarcinoma. SMARCA4 deletion is associated with a high rate of oncogene co-mutation. Co-mutation of KRAS was found to have a significant impact on the response to multiple types of chemotherapy. Unique metabolic profiles, abnormal cell cycle and hyperactivation of oxidative phosphorylation were hallmarks of SMARCA4 mutant LUAD. We screened four chemotherapeutic agents targeting MTOR pathway, oxidative stress, DNA replication or cell cycle, including rapamycin and ribociclib, as potential chemotherapeutic agents for SMARCA4-deficient lung adenocarcinoma. <em>In vitro</em> assays showed that SMARCA4 knockdown significantly inhibited DNA replication, cell cycle and cell proliferation in lung adenocarcinoma cells, and significantly promoted oxidative stress and apoptosis in lung adenocarcinoma cells. Our comprehensive findings advance our understanding of SMARCA4 mutant LUAD gene mutation and immune microenvironment, providing insights into potential therapeutic approaches and research directions for SMARCA4-deficient LUAD.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168051"},"PeriodicalIF":4.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066759","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":"Engineered oncolytic herpes simplex virus expressing interleukin 12 suppresses tumorigenicity of hepatocellular carcinoma","authors":"Jingwen Lv ,&nbsp;Wei Zhu ,&nbsp;Xin Xie ,&nbsp;Chao Tian ,&nbsp;Chengyang Zhu ,&nbsp;Zongfeng Hu ,&nbsp;Yixiao Li ,&nbsp;Mingxia Shao ,&nbsp;Wenqi Liu ,&nbsp;Di Ma ,&nbsp;Shengrun Wang ,&nbsp;Xiaopeng Li ,&nbsp;Jingfeng Li","doi":"10.1016/j.bbadis.2025.168033","DOIUrl":"10.1016/j.bbadis.2025.168033","url":null,"abstract":"<div><div>Oncolytic viruses (OVs) mediate anticancer effects through direct oncolytic activity and the expression of immunomodulatory transgenes. Talimogene laherparepvec (T-VEC), a genetically modified oncolytic herpes simplex virus type 1 (HSV-1) engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF), has received United States Food and Drug Administration (FDA) approval for melanoma treatment. However, the clinical efficacy of early generation OVs like T-VEC remains limited, highlighting the need to enhance their antitumor potency and immune activation capacity. Interleukin-12 (IL-12) is a potent immunostimulatory cytokine that promotes Th1-type responses, triggering interferon-γ production by natural killer (NK) cells, CD4⁺ T cells and CD8⁺ T cells, thereby exhibiting robust antitumor activity. In this study, we constructed two recombinant HSV-1, oHSV-GMCSF and oHSV-IL12, and evaluated their antitumor effects, alone or in combination, in H22 murine hepatocellular carcinoma (HCC) model. Strikingly, oHSV-IL12 monotherapy achieved complete tumor eradication, surpassing the efficacy of oHSV-GMCSF. RNA sequencing analysis revealed that oHSV-IL12 treatment enhanced intratumoral lymphocyte infiltration and activation while upregulating immune-related genes and pathways. Notably, the oHSV-IL12 monotherapy showed comparable therapeutic outcomes to the combination of oHSV-GMCSF and oHSV-IL12 in both rechallenge and survival experiments. These findings position oHSV-IL12 as a promising novel candidate for HCC immunotherapy.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168033"},"PeriodicalIF":4.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047038","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":"Unmasking the tumorigenic potential of cellular prion protein in cancer progression","authors":"Memoona Zahra ,&nbsp;Adi Idris ,&nbsp;Ming Q. Wei ,&nbsp;Nigel A.J. McMillan ,&nbsp;Alan L. Munn","doi":"10.1016/j.bbadis.2025.168049","DOIUrl":"10.1016/j.bbadis.2025.168049","url":null,"abstract":"<div><div>The cellular prion protein (PrP^C), altered forms of which are associated with neurological prion disorders, is overexpressed in gastric, breast, prostate, and colorectal cancer. Its overexpression affects cell proliferation, migration, and invasion, and confers resistance to chemotherapy. PrP^C is a prospective target for therapeutic and biomarker development and the study of PrP^C may offer new theoretical insights into cancer biology. This review explores the molecular mechanism by which PrP^C overexpression contributes to the promotion of cancer. We hypothesise that PrP^C may have a role in angiogenesis. We also consider the possible use of lipid nanoparticles as the therapeutic agent to target overexpressed PrP^C selectively in cancer. An improved knowledge of these molecular mechanisms may reveal additional targets for cancer treatment. Further research is required to elucidate these mechanisms and to formulate targeted interventions.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168049"},"PeriodicalIF":4.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042553","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":"Circadian regulation of vascular function: Metabolism as a link from molecular mechanisms to clinical implications","authors":"Fulin Wang ,&nbsp;Peng Yao ,&nbsp;Haifang Yu ,&nbsp;Lu Gan ,&nbsp;Yu Cao","doi":"10.1016/j.bbadis.2025.168048","DOIUrl":"10.1016/j.bbadis.2025.168048","url":null,"abstract":"<div><div>Circadian rhythms act as central coordinators of vascular physiology, synchronizing metabolic and hemodynamic processes across different vascular beds. Cell-autonomous clocks dynamically regulate vascular functions, including vasodilation and inflammatory responses, in endothelial cells, smooth muscle cells, and fibroblasts. Emerging evidence indicates extensive crosstalk with metabolic cell death pathways, particularly lipophagy-mediated lipid turnover, redox stress-triggered disulfidptosis, and glucotoxicity-induced metabolic collapse, all of which display circadian rhythmicity. Disruption of these pathways, such as in shift workers or individuals carrying clock gene mutation, significantly increases the risk of hypertension, atherosclerosis, and microvascular dysfunction. In this review, we highlight translational strategies that leverage circadian biology, including chronotherapy, pharmacological modulation of core circadian clock components, light-dark synchronization, and lifestyle interventions. We also emphasize that future research should aim to decode the spatiotemporal regulation of circadian-metabolic networks, which may offer novel insights for precision medicine approaches targeting vascular metabolic disorders.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168048"},"PeriodicalIF":4.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042591","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":"Piezo1 promotes M1 macrophage polarization and impairs osteogenic differentiation in bone infection","authors":"Rong-Shen Yang ,&nbsp;Shuan-Ji Ou ,&nbsp;Wei Zeng ,&nbsp;Yu-Dun Qu ,&nbsp;Jia-Xuan Li ,&nbsp;Jiang-Ping Wen ,&nbsp;Jia-Bao Liu ,&nbsp;Chang-Liang Xia ,&nbsp;Yong Qi ,&nbsp;Chang-Peng Xu","doi":"10.1016/j.bbadis.2025.168042","DOIUrl":"10.1016/j.bbadis.2025.168042","url":null,"abstract":"<div><h3>Background</h3><div>Bone infection induces a strong inflammatory response and leads to impaired bone regeneration, in which macrophages sense mechanistic signals and modulate immune responses in the inflammatory microenvironment through Piezo1. Nonetheless, the regulatory role of Piezo1 in macrophages during bone infection remains elusive.</div></div><div><h3>Methods</h3><div>Rat models of infected bone defects were established for bulk RNA sequencing and single-cell RNA sequencing. Tissues were collected from infected human bones and infected bone marrow cavity tissues of rats for in vivo validation. Indirect co-culture cell experiments were conducted using mouse mononuclear macrophages and mouse bone marrow mesenchymal stem cells for <em>in virto</em> validation.</div></div><div><h3>Results</h3><div>Piezo1 was upregulated in bone marrow macrophages during infection, driving M1 polarization and inflammatory cytokine secretion, which triggered PANoptosis and impaired the osteogenic differentiation of bone marrow mesenchymal stem cells. Piezo1 inhibition attenuated these effects, confirming its regulatory role.</div></div><div><h3>Conclusions</h3><div>Within the inflammatory microenvironment during infection, Piezo1 expression is increased in macrophages and mediates macrophage polarization toward M1 and pro-inflammatory cytokine secretion, inducing PANoptosis and impairing osteogenic differentiation in bone marrow mesenchymal stem cells. Targeting Piezo1-mediated crosstalk between macrophages and bone marrow mesenchymal stem cells offers a novel strategy for restoring bone regeneration in bone infection.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168042"},"PeriodicalIF":4.2,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031488","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":"Alpha-lipoic acid attenuates cardiac inflammation of CVB3 induced viral myocarditis via neutrophil-derived YM-1","authors":"Xiaoqi Wang ,&nbsp;Shuang Liu ,&nbsp;Di Su ,&nbsp;Jiayu Sui ,&nbsp;Xiangyu Yan ,&nbsp;Jia Yang ,&nbsp;Ziqi Zheng ,&nbsp;Penghe Wang ,&nbsp;Weijun Song ,&nbsp;Zexi Jin ,&nbsp;Mingyan E ,&nbsp;Maomao Zhang ,&nbsp;Bo Yu","doi":"10.1016/j.bbadis.2025.168034","DOIUrl":"10.1016/j.bbadis.2025.168034","url":null,"abstract":"<div><h3>Background and aims</h3><div>Viral myocarditis is an inflammatory pathology of the myocardium that involves innate immune responses, especially those involving neutrophils. However, strategies targeting neutrophils to alleviate inflammation have not achieved complete success. Alpha lipoic acid (ALA), a natural organosulfur compound, has the capacity to modulate immune cell behavior. This study aimed to investigate whether ALAs can regulate innate immunity to provide protection against coxsackievirus B3 (CVB3)-induced myocarditis.</div></div><div><h3>Methods and results</h3><div>Abdominal administration of ALA improved cardiac dysfunction and reduced mortality in a CVB3-induced mouse model of myocarditis (VM). ALA treatment induced neutrophils and inhibited Ly6C^hi pro-inflammatory macrophages, favoring a reparatory environment in the myocardium. However, depleting neutrophils with anti-Ly6G antibodies increased Ly6C^hi pro-inflammatory macrophage recruitment in blood and heart in ALA-treated VM mice. Further flow cytometry analysis indicated that ALA promoted Ym-1 expression of neutrophils. Blocking Ym-1 significantly reversed ALA-mediated cardiac reparative macrophages infiltration and cardiac function improvement post-VM. Recombinant Ym-1 drives macrophages toward a reparative phenotype and attenuates CVB3-induced viral myocarditis. Mechanistically, ALA reprogrammed neutrophil metabolic patterns, leading to increased production of the metabolite acetyl-CoA, thereby increasing the transcription of Ym-1 by promoting STAT6 acetylation.</div></div><div><h3>Conclusions</h3><div>ALA protects against VM by activating metabolic reprogramming/STAT6 acetylation/Ym-1 axis in neutrophils. These results highlight the heterogeneity of neutrophils and suggest that ALA might represent a feasible strategy to improve the prognosis of VM patients.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168034"},"PeriodicalIF":4.2,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027490","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 rs13045 reduces EIF2AK3 expression and inhibits pro-inflammatory cytokine secretion via the MAPK-ERK1/2 pathway in Kawasaki disease","authors":"Wan Yang ,&nbsp;Wenli Guo ,&nbsp;Zhouping Wang ,&nbsp;Linjie Jiang ,&nbsp;Xilian Luo ,&nbsp;Kaining Chen ,&nbsp;Xiaofang Liu ,&nbsp;Can An ,&nbsp;Lei Pi ,&nbsp;Yufen Xu ,&nbsp;Lanyan Fu ,&nbsp;Huazhong Zhou ,&nbsp;Xiaoqiong Gu ,&nbsp;Di Che ,&nbsp;Jianrui Wei ,&nbsp;Hongyan Yu","doi":"10.1016/j.bbadis.2025.168032","DOIUrl":"10.1016/j.bbadis.2025.168032","url":null,"abstract":"<div><h3>Purpose</h3><div>Kawasaki disease (KD) is an acute systemic vasculitis and a leading cause of acquired heart disease in children in developed countries. This study endeavors to explore the role and underlying mechanisms of EIF2AK3 in KD-related vasculitis, thereby offering novel therapeutic perspectives.</div></div><div><h3>Methods</h3><div>DNA from 910 KD patients and 848 controls were genotyped for <em>rs13045</em> using TaqMan® to analyze the association with KD susceptibility. Concurrently, EIF2AK3 expression under KD inflammatory conditions was assessed using qRT-PCR, Western blot, and immunofluorescence. Pro-inflammatory cytokine levels were measured following EIF2AK3 knockdown or overexpression, and RNA sequencing was explored the downstream signaling pathways. For in vivo experiment, a <em>Lactobacillus casei</em> cell wall extract (LCWE)-induced KD mouse model with Eif2ak3 knockdown was established. ELISA and HE staining were used to investigate the degree of vasculitis between Eif2ak3 knockdown and control groups.</div></div><div><h3>Results</h3><div>The <em>EIF2AK3</em>/<em>rs13045</em> polymorphism was associated with KD susceptibility, with the <em>rs13045</em> C allele downregulating EIF2AK3. EIF2AK3 expression was increased significantly during KD inflammatory conditions. EIF2AK3 knockdown or pharmacological inhibition (GSK2606414) reduced pro-inflammatory cytokines (IL-1β/IL-6/IL-8/TNF-α) expression, while overexpression of EIF2AK3 elevated them. Mechanistically, EIF2AK3 promoted pro-inflammatory cytokines expression through activation of the MAPK-ERK1/2 pathway. Furthermore, EIF2AK3 downregulation inhibited the endothelial-to-mesenchymal transition (EndoMT), thereby impairing HUVECs migration. These findings were also recapitulated in the KD mouse model.</div></div><div><h3>Conclusion</h3><div><em>EIF2AK3</em>/<em>rs13045</em> is a novel susceptibility locus for KD in the southern Chinese population. Our findings reveal that EIF2AK3 upregulates pro-inflammatory cytokines, thereby promoting KD-associated vasculitis via the MAPK-ERK1/2 pathway. This discovery suggests EIF2AK3 as a potential therapeutic target for the management of KD.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168032"},"PeriodicalIF":4.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006983","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":"ClC-3 inhibition induces autophagy to reverse cisplatin resistance in cervical cancer via the Akt/mTOR pathway","authors":"Jiayi Shen ,&nbsp;Duoyi Zhang ,&nbsp;Qi Zheng ,&nbsp;Zhiyun Zhang ,&nbsp;Tianhong Zhu ,&nbsp;Yongming Du ,&nbsp;Fubin Zhang ,&nbsp;Yutao Guan","doi":"10.1016/j.bbadis.2025.168030","DOIUrl":"10.1016/j.bbadis.2025.168030","url":null,"abstract":"<div><div>Cervical cancer is one of the most prevalent types of cancer among women. Nowadays, surgery is still the primary treatment for cervical cancer. Cisplatin was regarded as the standard medication for non-surgical therapy. Unfortunately, some patients respond poorly to cisplatin, resulting in a significantly reduced survival rate. Our earlier study revealed that chloride channel-3 (ClC-3) is highly expressed in cervical cancer and other researchers revealed a tight relationship between ClC-3 and autophagy-induced chemoresistance in different tumor types. Consequently, the purpose of this article is to figure out the link between ClC-3-related autophagy and cisplatin sensitivity in cervical cancer. We discovered that inhibiting ClC-3 expression could enhance the sensitivity of cervical cancer cell line (SiHa) to cisplatin and even reverse the cisplatin resistance in a cisplatin-resistant cervical cancer cell line (SiHa/DDP). This process was initiated by the cell autophagy which the Akt-mTOR pathway mediated. A ClC-3 specific inhibitor (Chlorotoxin TFA, CLTX) made cervical cancer xenograft implantation more sensitive to cisplatin in vivo. All these findings revealed the mechanism and connection between ClC-3 and cisplatin sensitivity in cervical cancer, as well as provided new light into the application of the ClC-3 specific inhibitor for cisplatin sensitization in cervical cancer.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 1","pages":"Article 168030"},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002098","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}