Current molecular medicine最新文献

{"title":"SSR2 Promotes Sorafenib Resistance Via Interacting with GPX4 to Inhibit Ferroptosis.","authors":"Zebing Song, Mengdan Zhou, Xiaodong Song, Hongyun Jia, Xuewei Yang","doi":"10.2174/0115665240405981251201125139","DOIUrl":"https://doi.org/10.2174/0115665240405981251201125139","url":null,"abstract":"<p><strong>Aim & objectives: </strong>Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Understanding the regulatory mechanisms of sorafenib resistance is critical to inhibit sorafenib resistance and develop novel therapeutic strategies. Here, we aimed to study the role of SSR2 (signal sequence receptor subunit 2) in sorafenib resistance of HCC.</p><p><strong>Methods: </strong>3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and cell viability assay were used to determine the role of SSR2 in sorafenib resistance of HCC. Co-immunoprecipitation (CoIP) was used to determine the interacting protein of SSR2.</p><p><strong>Results: </strong>We found SSR2 was upregulated in sorafenib-resistant HCC tissues. In addition, in HCC patients, SSR2 was associated with both poor response to sorafenib and poor clinical outcomes. Functional assay showed that SSR2 promoted sorafenib resistance in HCC cells. Mechanistically, SSR2 suppressed ferroptosis. Further analysis showed that SSR2 interacted with ferroptosis master regulator glutathione peroxidase 4 (GPX4) and increased the catalytic activity of GPX4, leading to inhibition of ferroptosis. Induction of ferroptosis could reverse the promotion effect of SSR2 overexpression on sorafenib resistance.</p><p><strong>Discussion: </strong>SRR2 plays a critical role in sorafenib resistance generation. However, the detailed mechanism of SRR2 increasing the catalytic activity of GPX4 will be further studied.</p><p><strong>Conclusions: </strong>In summary, we reveal that SSR2 enhances sorafenib resistance of HCC via interacting with GPX4 and inhibiting ferroptosis, providing a potential target for HCC treatment. The molecular mechanism of GPX4-SSR2 interaction in ferroptosis will be further studied.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Cuproptosis-related lncRNA Signature for Prognostic Stratification and Immunotherapeutic Implications in Lung Adenocarcinoma.","authors":"Yanan Jiang, Donghui Xing, Kaiping Luo, Jing Guo, Yixin Zhai, Cheng Li, Xiang He, Jinhuan Wang, Wenqi Wu, Zhigang Zhao","doi":"10.2174/0115665240355806250718044011","DOIUrl":"https://doi.org/10.2174/0115665240355806250718044011","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, and there have been disputes over its prognostic biomarker and clinical outcome. Cuproptosis, a novel form of regulated cell death (RCD), has been insufficiently explored in terms of its potential role in LUAD.</p><p><strong>Methods: </strong>In this study, we developed a machine learning-based integrative procedure for constructing a consensus cuproptosis-related lncRNA signature (CTLNS) using TCGA data and validated it with external datasets.</p><p><strong>Results: </strong>The CTLNS was identified as an independent predictor of overall survival, showing stable and accurate performance across multiple cohorts. Patients classified into high- and low-risk groups exhibited significant differences in survival outcomes. Functional analyses revealed that the low-risk group was enriched in DNA replication and immune-related pathways, while the high-risk group was associated with oncogenic signaling and cell cycle regulation. Notably, high-risk patients showed increased sensitivity to several chemotherapy agents, including Docetaxel, Cisplatin, Gefitinib, and Paclitaxel, while low-risk patients were more responsive to Nilotinib.</p><p><strong>Conclusion: </strong>These findings suggest that CTLNS is a reliable biomarker for prognostic prediction and treatment stratification in LUAD, offering potential utility in personalized therapy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the TRIM Family in Lung Cancer Development: An Emerging Player with Therapeutic Potential.","authors":"Jinxin Li, Yiling Wang, Jinbai Huang, Wei Wang, Dezhou Cheng, Qing Yang, Xiaochun Peng","doi":"10.2174/0115665240377498250614100838","DOIUrl":"10.2174/0115665240377498250614100838","url":null,"abstract":"<p><p>Lung cancer is one of the most prevalent malignancies and a leading cause of cancer-related deaths worldwide. E3 ubiquitin ligase activity is a common feature of most TRIM proteins, highlighting the family's critical role in regulating the biological behaviors of tumor cells and influencing various cellular physiological activities, including apoptosis, innate immunity, development, and intracellular signaling. In lung cancer, certain TRIM proteins function either as oncoproteins or cancer suppressors. This review explores the unique function of TRIM in lung cancer development, focusing on the molecular processes of TRIM proteins. Finally, we provide an overview of recent advancements in the prognosis and therapeutic strategies for lung cancer involving TRIM proteins.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"547-563"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota-induced Long Non-coding RNA Snhg9 Regulates the Development of Human Malignant Tumors.","authors":"Dengke Jia, Yaping He, Qianle Chen, Yawu Zhang","doi":"10.2174/0115665240366916250629064055","DOIUrl":"10.2174/0115665240366916250629064055","url":null,"abstract":"<p><p>Gut microbes influence the progression of human malignancies through their recognition by the immune system and their effects on numerous metabolic pathways. Long non-coding RNA is a key target of intestinal microbiota involved in the progression of human malignant tumors. Current research shows that there is a close cross-talk between long non-coding RNA Snhg9 and intestinal microorganisms, and it is widely involved in the progression of human malignant tumors. An in-depth study of the interaction between long non-coding RNA and intestinal flora and the intrinsic regulatory mechanism of snhg9 will provide new and powerful therapeutic targets for future research on human malignant tumors.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"663-673"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of Platinum-based Drug Sensitivity in Ovarian Cancer Cells Through Hyperthermia-induced Activation of the TGF-β1/β-Catenin Signaling Pathway.","authors":"Xiaogang Lv, Wenjuan Wu, Gaoting Huang, Xiaowen Yao, Shirong Zeng, Yifeng Wang","doi":"10.2174/0115665240367566250327040010","DOIUrl":"10.2174/0115665240367566250327040010","url":null,"abstract":"<p><strong>Background: </strong>Platinum-based drugs like cisplatin are key in treating ovarian cancer, but resistance frequently leads to treatment failure. The TGF-β1/β- catenin signaling pathway has been implicated in tumor resistance. This study investigates whether hyperthermiaenhances ovarian cancer cell sensitivity to platinum-based drugs by activating the TGF-β1/β-catenin pathway.</p><p><strong>Methods: </strong><i>In vitro</i> and <i>in vivo</i> models of ovarian cancer were treated with hyperthermia and cisplatin. Changes in TGF-β1 and β -catenin expression were measured using Western blotting, qPCR, immunohistochemistry, and cell viability assays to determine the impact of hyperthermia on drug sensitivity.</p><p><strong>Results and discussion: </strong>Hyperthermia significantly reduced TGF-β1 and β-catenin expression in ovarian cancer cells and tumor tissues, suppressing the pathway. This led to increased cisplatin sensitivity and higher apoptosis rates <i>in vitro</i>, while in vivo, tumor growth was significantly suppressed, and cisplatin's antitumor effects were enhanced.</p><p><strong>Conclusion: </strong>Hyperthermia boosts the effectiveness of platinum-based drugs in ovarian cancer by suppressing the TGF-β1/β-catenin pathway, presenting a potential strategy to overcome chemoresistance and improve patient outcomes.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"184-193"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-9-5p Alleviates Oxidative Stress, Inflammation, and Apoptosis in Cerebral Ischemia-reperfusion Injury by Targeting NOX4 <i>In vitro</i>.","authors":"Yuan Huang, Xiaoli Hou, Yixia Wang, Yasen Cao, Yan Zhou, Yu Chen, Hong Cheng","doi":"10.2174/0115665240337045241210064142","DOIUrl":"10.2174/0115665240337045241210064142","url":null,"abstract":"<p><strong>Background: </strong>Prior research has displayed that the dysregulation of miR- 9-5p is related to cerebral ischemia-reperfusion (I/R) injury. However, the underlying neuroprotective mechanism of miR-9-5p in cerebral I/R injury has not been clarified.</p><p><strong>Materials and methods: </strong>The cerebral I/R injury was simulated by oxygen-glucose deprivation/reperfusion (OGD/R) model that was constructed in human SH-SY5Y cells. Changes in reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were detected with the commercial kits. ELISA assay was applied for measuring the expressions of inflammatory cytokines. Western blot was used for testing the protein levels. Cell apoptosis was measured by TUNEL assay.</p><p><strong>Results and discussion: </strong>MiR-9-5p expression was dramatically decreased, while NADPH oxidase 4 (NOX4) expression was significantly increased in SH-SY5Y cells under OGD/R operation. MiR-9-5p over-expression dramatically inhibited OGD/Rinduced oxidative stress, inflammation, and apoptosis in SH-SY5Y cells. Mechanistically, results from luciferase reporter assay demonstrated that NOX4 was a target of miR-9-5p, and NOX4 over-expression partially reversed the effects of miR-9-5p mimic on oxidative stress, inflammation, and apoptosis in OGD/R SHSY5Y cells.</p><p><strong>Conclusion: </strong>MiR-9-5p over-expression suppressed oxidative stress, inflammation, and apoptosis in cerebral I/R injury by targeting NOX4, suggesting that miR-9-5p might be a new anti-inflammatory and anti-oxidative modulator in cerebral I/R injury.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"79-87"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Glycolysis and Lipid Metabolism Status Predicts Poor Prognosis in Colorectal Cancer Patients.","authors":"Meng Li, Maoyi Yue, Yao Chen, Gang Zhao","doi":"10.2174/0115665240369037250319000043","DOIUrl":"10.2174/0115665240369037250319000043","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of patients with stage III colorectal cancer (CRC) shows significant variations. The purpose of this study was to investigate the role of key regulatory proteins in glycolysis and lipid metabolism for the prognostic evaluation of stage III CRC patients.</p><p><strong>Methods: </strong>Utilizing the Cancer Genome Atlas (TCGA) database, we analyzed the expression of various key regulatory genes in glycolysis and lipid metabolism pathways in CRC, as well as the relationship between gene expression levels and overall survival.. We selected the top two key genes exhibiting differential expression patterns in glycolysis and lipid metabolism, namely, glucose transporter type 1 (GLUT1), pyruvate kinase M2 (PKM2), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1), as targets for subsequent exploration. We analyzed the effects of GLUT1, PKM2, FASN, and SCD1 on the proliferation, migration, and drug sensitivity of CRC cells in vitro. These proteins were detected by immunohistochemistry (IHC) in the clinical tissues of stage III CRC patients. Based on the intensity of IHC staining for GLUT1, PKM2, FASN and SCD1, the cumulative score from these 4 target proteins for each sample was calculated (score range from 0 to 8). The relationships between high (scores of 6-8) or low (scores of 0-5) expression of glycolysis and lipid metabolism molecules and the clinicopathological characteristics, and survival of patients were analyzed.</p><p><strong>Results: </strong>The expression disparities of the GLUT1, PKM2, FASN, and SCD1 genes were the most prominent between tumor and normal tissues. Overexpression of GLUT1, PKM2, FASN, or SCD1 significantly promoted CRC cell growth and migration, as evidenced by CCK-8, colony formation, and Transwell assays. Exogenous introduction of GLUT1, PKM2, FASN, or SCD1 increased oxaliplatin IC₅₀ values, enhanced cell survival, and reduced early apoptosis in CRC cells exposed to oxaliplatin. High glycolysis and lipid metabolism status were associated with poor tumor differentiation, vascular or nerve invasion, and shorter overall survival. The status of glycolysis and lipid metabolism was an independent prognostic factor for stage III CRC patients.</p><p><strong>Discussion: </strong>Based on IHC staining of GLUT1, PKM2, FASN, and SCD1, we established a protein-based scoring system to classify stage III CRC patients into high or low glycolipid metabolism groups. This scoring system provides a practical and objective method for prognostic assessment, offering potential guidance for treatment strategies in stage III CRC patients.</p><p><strong>Conclusion: </strong>High glycolysis and lipid metabolism status are correlated with a poor prognosis in patients with stage III colorectal cancer.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"170-183"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface.","authors":"Andras Guttman","doi":"10.2174/0115665240453235251118061700","DOIUrl":"10.2174/0115665240453235251118061700","url":null,"abstract":"","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"i-ii"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tamoxifen and Colchicine Alter Mitochondrial Respiration to Induce Cell Death in Low-metastatic Breast Cancer Cells.","authors":"Tashvinder Singh, Amitha Thankachan, Anjana Munshi, Sandeep Singh","doi":"10.2174/0115665240344743251210121414","DOIUrl":"https://doi.org/10.2174/0115665240344743251210121414","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer cells exhibit mitochondrial respiration-mediated metabolic heterogeneity and tumour aggressiveness. Tamoxifen and Colchicine are known to interfere with oxidative stress in breast cancer cells. However, their role in regulating mitochondrial respiration remains poorly understood.</p><p><strong>Methods: </strong>MCF7 and MDA-MB-231 cells were used to analyse the metabolic modulatory effects of Tamoxifen and Colchicine. The roles of Tamoxifen and Colchicine in regulating ROS production, mitochondrial membrane potential, mitochondrial membrane integrity, and oxidative phosphorylation were assessed using ROS assay, JC-1 assay, and high-resolution respirometry, respectively. Their effects on mitochondrial biogenesis and mitochondria-dependent cytotoxicity were analysed using flow cytometry and confocal microscopy.</p><p><strong>Results: </strong>Tamoxifen and Colchicine exhibited cytotoxic effects by reducing ROS production, depolarising mitochondrial membrane potential, decreasing oxygen consumption, and inhibiting mitochondrial respiration. They specifically downregulated pyruvate-mediated mitochondrial respiration, preventing N-linked state mitochondrial respiration and reducing complex I activity. Colchicine demonstrated mitochondrialindependent cytotoxic effects, whereas Tamoxifen did not. Neither drug impacted mitochondrial membrane integrity. Tamoxifen and Colchicine decreased leak respiration, inhibited proton and electron transfer, and prevented non-phosphorylating electron transfer, potentially due to reduced complex I activity. Tamoxifen significantly inhibits mitochondrial biogenesis and induces a mitochondrial-dependent cell death pathway. In contrast, Colchicine had a low impact on mitochondrial biogenesis and induced a mitochondrial-independent cell death pathway.</p><p><strong>Discussion: </strong>Tamoxifen and colchicine suppress complex I-driven mitochondrial respiration in breast cancer cells, reducing oxidative phosphorylation-associated aggressiveness. Notably, only tamoxifen links this metabolic inhibition to impaired mitochondrial biogenesis and mitochondria-dependent cytotoxicity.</p><p><strong>Conclusion: </strong>Tamoxifen and colchicine downregulate mitochondrial respiration and biogenesis, while only tamoxifen induces mitochondrial-dependent cytotoxicity.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":"26 5","pages":"516-528"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise Alleviates Atherosclerosis Through the Modulation of the NLRP3 Inflammasome.","authors":"Xuan Liu, Shujuan Hu, Xianwang Wang, Yuqing Ding","doi":"10.2174/0115665240368171250419113225","DOIUrl":"10.2174/0115665240368171250419113225","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory disease closely associated with endothelial dysfunction and oxidative stress. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key regulator of inflammatory responses, can exacerbate the progression of AS when activated. Growing evidence suggests that exercise, as a non-pharmacological intervention, can alleviate the progression of AS by modulating the activity of NLRP3 inflammasome. This review discusses how exercise influences the development of AS through the regulation of NLRP3 inflammasome and the underlying molecular mechanism. This study introduces the structure and activation mechanisms of NLRP3 inflammasome, as well as its role in AS. And summarizes how exercise can ameliorate endothelial dysfunction, regulate lipid metabolism, and suppress oxidative stress and inflammation by affecting the expression and activity of NLRP3 inflammasome, thereby exerting a beneficial impact on AS. Additionally, we explore the effects of exercise on the downstream inflammatory cytokines of NLRP3 inflammasome and how this regulation could help to slow the progression of AS. These findings underscore the therapeutic relevance of exercise in the prevention and treatment of AS. It provides new insights into the role of exercise interventions in the management of AS and lays a theoretical foundation for the development of innovative treatment strategies for cardiovascular disease. Given that the NLRP3 inflammatome plays an important role in the pathogenesis and treatment of AS, exercise therapy strategies targeting the NLRP3 inflammatome will help promote the development of precision medicine for AS.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"358-375"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}