Experimental cell research最新文献

{"title":"Berberine overcomes paclitaxel resistance in triple-negative breast cancer by inhibiting HSP90-mediated BRCA1 phosphorylation","authors":"Jingyi Li ,&nbsp;Xinping Zhu ,&nbsp;Liang Feng ,&nbsp;Xiaoqin Liu ,&nbsp;YuQin Xiao ,&nbsp;Yanting Zhang ,&nbsp;Changlian Lu ,&nbsp;Weiming Zhao","doi":"10.1016/j.yexcr.2025.114815","DOIUrl":"10.1016/j.yexcr.2025.114815","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, and chemotherapy remains a major component of the standard therapy. Although there is an initial response, the tumor will inevitably develop resistance to paclitaxel (PTX) treatment. Berberine (BBR) exhibits excellent anti-cancer activity in a variety of tumor cells and drug-resistant tumor cells. In the in vitro experiments of the study, the effect of BBR on PTX resistance was explored through proliferation assay, flow cytometry. The effects of combined treatment of BBR and PTX on DNA damage in TNBC cells were evaluated by colony formation assay, comet assay and γ-H2AX staining. Western blot and immunofluorescence revealed that HSP90 was highly expressed in the tolerant strain. BBR promotes the ubiquitination and degradation of HSP90 through the ubiquitin-protease system, further inhibits the expression of its client protein p-BRCA1 and improves the sensitivity of PTX treatment. Cell lines overexpressing hsp90 were constructed and it was found that Hsp90 could reverse the sensitivity of BBR to PTX. In addition, a model of transplanted tumors in nude mice was constructed to further verify the regulatory effect of BBR on PTX resistance in TNBC. Collectively, our findings demonstrate that BBR targets HSP90 to activate p-BRCA1-mediated DNA damage, thereby sensitizing non-BRCA-mutated TNBC to PTX. These results suggest HSP90 inhibition as a therapeutic strategy to circumvent chemotherapy resistance and a potential biomarker for predicting TNBC treatment response.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 1","pages":"Article 114815"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458049","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":"Effects of everolimus on circadian gene expression and cell fate in synchronized Caco-2 cells","authors":"Dilek Ozturk Civelek ,&nbsp;Beyza Goncu ,&nbsp;Sadullah Goncu ,&nbsp;Alper Okyar","doi":"10.1016/j.yexcr.2025.114810","DOIUrl":"10.1016/j.yexcr.2025.114810","url":null,"abstract":"<div><h3>Objectives</h3><div>Circadian rhythms regulate key biological processes, including cell proliferation and metabolism, and their disruption is implicated in colorectal cancer (CRC). mTOR signaling interacts bidirectionally with the circadian clock, yet how mTOR inhibition modulates clock gene dynamics and cellular behavior in intestinal models remains unclear. This study aimed to investigate the effects of everolimus, an mTOR inhibitor, on circadian gene expression, cell viability, apoptosis, and cell cycle progression in synchronized Caco-2 cells, with consideration of cell confluency and Circadian Time (CT).</div></div><div><h3>Methods</h3><div>Caco-2 cells were synchronized using serum shock at 20 % and 70 % confluency. Time-series samples were collected across multiple CTs (CT6–CT60). Gene expression (<em>BMAL1, PER2, mTOR</em>) was assessed by qRT-PCR using <em>ACTB</em> and <em>RPLP0</em> as reference genes. Rhythmicity was evaluated via Cosinor analysis. Cell viability, apoptosis, and cell cycle dynamics were analyzed using the Muse™ Cell Analyzer following everolimus treatment (1–50 μM).</div></div><div><h3>Results</h3><div><em>RPLP0</em> proved to be a more stable reference gene than <em>ACTB</em>. <em>BMAL1</em> exhibited stronger rhythmic expression than <em>PER2</em>, particularly at 20 % confluency. Everolimus (50 μM) significantly reduced cell viability in a time-dependent manner, with the greatest effect at CT6 and CT18 (p &lt; 0.0001). Apoptosis was markedly increased at CT6 (+38.5 %) and moderate at CT18, indicating circadian modulation of drug sensitivity. Serum shock alone shifted cell cycle distribution, decreasing G0/G1 and increasing G2/M phase populations (p &lt; 0.01). Everolimus altered <em>BMAL1</em> and <em>PER2</em> expression rhythms and significantly reduced mTOR expression at CT30, where baseline mTOR levels were highest. Cosinor analysis confirmed rhythmicity in <em>BMAL1/RPLP0</em> and <em>mTOR/RPLP0</em> profiles under low confluency.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that everolimus influences circadian gene expression and exerts time-dependent antiproliferative and pro-apoptotic effects in Caco-2 cells. These results support the potential of circadian timing as a strategy to enhance mTOR-targeted therapies in CRC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114810"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414066","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":"EIF4A3-mediated localization of circDNAJC16 sequesters miR-93-5p to suppress lung adenocarcinoma progression via CDKN1A-regulated cell cycle and EMT","authors":"Liu Yang ,&nbsp;Yaodong Fan ,&nbsp;Yiyin Wang ,&nbsp;Chuntao Yan ,&nbsp;Zheng Guan ,&nbsp;Yuan Li ,&nbsp;Xiaosan Su ,&nbsp;Xiaowei Huang","doi":"10.1016/j.yexcr.2025.114799","DOIUrl":"10.1016/j.yexcr.2025.114799","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD), the predominant non-small cell lung cancer subtype, exhibits high mortality due to metastasis and therapeutic resistance. While circular RNAs (circRNAs) are implicated in oncogenesis, their functional mechanisms and upstream regulation in LUAD remain incompletely characterized. This study identifies <strong>circDNAJC16 (hsa_circ_0000018)</strong> as significantly downregulated in advanced-stage LUAD (Stage III-IV vs. I-II, <em>p</em> = 0.001), where its low expression independently predicts poor survival (HR = 1.93, <em>p</em> = 0.043). Functional characterization demonstrates that circDNAJC16 overexpression suppresses <em>in vivo</em> tumor growth (volume reduction: 26.56 %, <em>p</em> &lt; 0.001) through cytoplasmic sequestration of <strong>oncogenic miR-93-5p</strong>, thereby activating <strong>CDKN1A/p21</strong> to induce G0/G1 cell cycle arrest and inhibit proliferation, while concurrently suppressing metastasis via epithelial-mesenchymal transition (EMT) regulation. Crucially, the RNA-binding protein <strong>eIF4A3</strong> binds upstream flanking introns of the host DNAJC16 pre-mRNA, driving selective nuclear retention of circDNAJC16 and redirecting linear DNAJC16 mRNA to the cytoplasm – a bifurcation mechanism essential for tumor suppression. These findings identify circDNAJC16 downregulation as a negative prognostic indicator in LUAD and reveal its dual tumor-suppressive roles: cytoplasmic sequestration of miR-93-5p activating CDKN1A-mediated cell cycle arrest, coupled with eIF4A3-governed nuclear retention controlling functional subcellular localization. Significantly, this work is the first to demonstrate eIF4A3-mediated circRNA compartmentalization, establishing circDNAJC16 as a novel prognostic biomarker and therapeutic target for LUAD.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114799"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370111","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":"FERMT1 suppresses the ferroptosis of glioma cells by interacting with MBOAT2","authors":"Zhigang Pan ,&nbsp;Chuhan Ke ,&nbsp;Bojun Zhang ,&nbsp;Qingxin Lin ,&nbsp;Hanlin Zheng ,&nbsp;Shuni Zheng ,&nbsp;Jinzhong Huang ,&nbsp;Weipeng Hu","doi":"10.1016/j.yexcr.2025.114794","DOIUrl":"10.1016/j.yexcr.2025.114794","url":null,"abstract":"<div><div>Gliomas, particularly high-grade glioblastomas, are highly aggressive malignancies with limited treatment options and poor prognosis. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic target in cancer. However, the mechanisms regulating ferroptosis in glioma remain poorly understood. In this study, we identify FERMT1 as a key suppressor of ferroptosis in glioma cells. Using gain and loss-of-function experiments, we demonstrate that FERMT1 overexpression protects glioma cells from erastin-induced ferroptosis, while FERMT1 deficiency sensitizes cells to ferroptotic cell death. Treatment with the ferroptosis inhibitor ferrostatin-1 mitigates the effects of FERMT1 deficiency, underscoring the importance of ferroptosis suppression in FERMT1-mediated oncogenesis. Mechanistically, FERMT1 interacts with MBOAT2 to suppress ferroptosis. Depletion of MBOAT2 abolishes the anti-ferroptotic effects of FERMT1, whereas MBOAT2 overexpression rescues ferroptosis in FERMT1-deficient cells. Collectively, our findings reveal a previously unrecognized FERMT1-MBOAT2 axis that regulates ferroptosis in glioma cells and provide new insights into the molecular mechanisms underlying glioma progression. Targeting this axis may offer a novel therapeutic strategy for inducing ferroptosis and improving treatment outcomes in glioma.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114794"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299451","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":"Intraindividual rDNA copy number variation and methylation in humans","authors":"Jana Durackova ,&nbsp;Ramya Potabattula ,&nbsp;Andreas Rosenwald ,&nbsp;Thomas Haaf","doi":"10.1016/j.yexcr.2025.114793","DOIUrl":"10.1016/j.yexcr.2025.114793","url":null,"abstract":"<div><div>The absolute number of rDNA transcription units (TU) can vary by about one order of ten among individuals. Apart from extensive rDNA copy number (CN) variation and instability in many cancers, there is little information on the extent of intraindividual CN variation between normal tissues. Here we used droplet digital PCR and deep bisulfite sequencing to determine both the absolute rDNA CN and the number of presumably active CN with a hypomethylated (≤10 %) promoter region in up to six different tissues of 13 autopsy probands. In general, the absolute rDNA CN as well as the frequency of the minor A variant were highly similar between tissues (cerebellum, cerebrum, colon, heart, intestine, kidney, liver, and spleen) of the same individual. However, in some probands absolute CN in one or multiple tissues was much higher than in the other tissues, indicative of relaxation/breakdown of the CN control system. The amplified copies were inactivated by promoter methylation and, thus, the number of active CN was largely independent from absolute CN. Collectively, our data suggest that with some notable exceptions absolute and even more active rDNA CN are maintained during development and differentiation in different tissues of the same individual. Despite the low intraindividual variation active CN appeared to systematically vary between tissues. Cerebellum and cerebrum consistently exhibited lower active CN than the other analyzed tissues. We estimate that &gt;50 active rDNA TU are required for normal tissue/organ function.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114793"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299428","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":"A tRNA-derived fragment tiRNA-Met-CAT-002 induced by myocardial ischemia/reperfusion injury inhibits cardiomyocyte autophagy by regulating Bnip3","authors":"Lang Deng ,&nbsp;Yawen Weng ,&nbsp;Jiahui Lin ,&nbsp;Lingfeng Zhong ,&nbsp;Zhixuan Tang ,&nbsp;Shuang Lin ,&nbsp;Weijian Huang ,&nbsp;Zhenfeng Cheng ,&nbsp;Kongjie Lu ,&nbsp;Bozhi Ye","doi":"10.1016/j.yexcr.2025.114809","DOIUrl":"10.1016/j.yexcr.2025.114809","url":null,"abstract":"<div><div>Myocardial ischemia/reperfusion (I/R) injury is a significant contributor to the development of heart failure. This study investigates the differential expression of tRNA-derived small RNAs (tsRNAs) during I/R and explores their potential functional implications. Through tRF &amp; tiRNA sequencing, we identified 115 tsRNAs exhibiting significant changes in expression following I/R. Notably, tiRNA-Met-CAT-002 was found to be upregulated via the hypoxia/hypoxia-inducible factor 1 subunit α (HIF1α)/angiogenin (ANG) signaling axis. Our findings suggest that Bnip3 represents a crucial target for tiRNA-Met-CAT-002. Mechanistically, mimics of tiRNA-Met-CAT-002 reduced Bnip3 protein expression by directly targeting the 3′ untranslated region (UTR) of its mRNA in a manner resembling microRNA activity. Furthermore, tiRNA-Met-CAT-002 was observed to decrease autophagy levels while enhancing cell viability under hypoxia/reoxygenation (H/R) conditions. In conclusion, this study underscores the substantial role of tsRNAs in the pathophysiology of I/R injury, with tiRNA-Met-CAT-002 potentially serving as a protective factor by attenuating autophagy levels.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114809"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145360731","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":"Bone marrow mesenchymal stem cell-derived exosomes HADH alleviate vitiligo by activating the Nrf2/HO-1 pathway","authors":"Shiyang Tang ,&nbsp;Xin Li ,&nbsp;Jianyuan Xi","doi":"10.1016/j.yexcr.2025.114798","DOIUrl":"10.1016/j.yexcr.2025.114798","url":null,"abstract":"<div><h3>Background</h3><div>Vitiligo is a chronic skin disorder that significantly impairs patients' quality of life. Exosomes (Exos) have been reported to hold therapeutic promise for vitiligo. This study aimed to investigate the molecular mechanism by which bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) ameliorate vitiligo.</div></div><div><h3>Methods</h3><div><em>In vitro</em> vitiligo cell model was established by hydrogen peroxide (H₂O₂)-induced melanocytes. A mouse model of vitiligo was also established. Immunofluorescence, cell counting kit-8, 2′,7′-dichlorofluorescein diacetate, enzyme linked immunosorbent assay, flow cytometry, real-time quantitative PCR, western blotting, hematoxylin-eosin, Masson-Fontana, and immunohistochemistry staining experiments were elucidated to explore the molecular mechanism of BMSC-Exos in relieving vitiligo.</div></div><div><h3>Results</h3><div>H₂O₂ treatment reduce the cell viability, superoxide dismutase and catalase activities, and promote reactive oxygen species production, pyroptosis, the expression of NLRP3, ASC, IL-1β and IL-18 proteins in melanocytes. BMSC-Exos treatment effectively counteracted these detrimental effects. Knockdown of exosomal HADH derived from BMSC enhanced H₂O₂-induced oxidative stress and pyroptosis in melanocytes. Mechanistically, BMSC-Exos attenuated H₂O₂-induced oxidative stress and pyroptosis by mediating HADH delivery to activate the Nrf2/HO-1 pathway. Moreover, these results were further confirmed by experiments in a mouse model of vitiligo.</div></div><div><h3>Conclusion</h3><div>BMSC-Exos can alleviate vitiligo by delivering HADH to activate the Nrf2/HO-1 pathway. This study provides insights for exploring new treatments for vitiligo.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114798"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312758","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":"Activation of STING sensitizes melanoma cells to radiation through ROS-induced NLRP3","authors":"Jiajia Wang ,&nbsp;Shaokai Tang ,&nbsp;Tingyi Yang ,&nbsp;Fenghao Geng ,&nbsp;Xiaoyou Tang ,&nbsp;Rui Xia ,&nbsp;Xin Zhang ,&nbsp;Hao Bai ,&nbsp;Hai Xiong ,&nbsp;Daojiang Yu ,&nbsp;Shuyu Zhang","doi":"10.1016/j.yexcr.2025.114811","DOIUrl":"10.1016/j.yexcr.2025.114811","url":null,"abstract":"<div><h3>Background</h3><div>Melanoma is an aggressive malignancy with one of the highest mortality rates among skin cancers. Radiotherapy is a common treatment modality, but radioresistance remains a significant challenge. The stimulator of interferon genes (STING) pathway has been implicated in antitumor immunity and cancer treatment, yet its role in melanoma radiosensitivity is poorly understood.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the role of STING in enhancing the radiosensitivity of cutaneous melanoma cells and to explore the underlying mechanisms involving reactive oxygen species (ROS) and the NLRP3 inflammasome.</div></div><div><h3>Methods</h3><div>Using TCGA database analysis, we examined the correlation between cGAS-STING pathway expression and melanoma patient survival. In vitro experiments were conducted on A375 and B16F10 melanoma cell lines, where STING was overexpressed or activated using the STING agonist cGAMP. Cell viability, apoptosis, ROS levels, and NLRP3/ASC complex activity were assessed following radiation treatment. In vivo studies involved tumor-bearing mice treated with cGAMP and radiation to evaluate tumor growth and survival.</div></div><div><h3>Results</h3><div>High expression of cGAS and STING was associated with improved survival in melanoma patients. STING overexpression or cGAMP treatment significantly reduced cell viability, increased ROS levels, and enhanced apoptosis in irradiated melanoma cells. Mechanistically, the activation of STING elevated NLRP3/ASC complex activity, and the NLRP3 inhibitor CY-09 reversed the radiosensitization effects. In vivo, cGAMP combined with radiation suppressed tumor growth and improved survival in melanoma-bearing mice.</div></div><div><h3>Conclusion</h3><div>STING enhances radiosensitivity of melanoma through ROS-NLRP3 axis, and combining STING agonists with radiotherapy may be a new strategy to overcome radioresistance.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114811"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414065","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":"Integrative multi-omics analysis identifies mitochondria- and ferroptosis-related prognostic genes in cervical cancer","authors":"Linlin Jia ,&nbsp;Xinyu Cui ,&nbsp;Xiaoting Li ,&nbsp;Rui Li","doi":"10.1016/j.yexcr.2025.114796","DOIUrl":"10.1016/j.yexcr.2025.114796","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondria and ferroptosis are crucial in tumorigenesis. However, their specific role in cervical cancer (CC) remains unclear. This study aimed to identify and validate prognostic genes linked to mitochondrial function and ferroptosis in CC.</div></div><div><h3>Methods</h3><div>Publicly available datasets were analyzed, including 306 CC tumor samples from The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC), with survival data for 293 samples, a training set of 24 normal and 33 tumor tissues (GSE9750), and a validation set of 300 tumor tissues (GSE44001). Prognostic genes associated with mitochondria-related genes (MRGs) and ferroptosis-related genes (FRGs) were identified through machine learning, univariate Cox regression, Weighted Gene Co-expression Network Analysis (WGCNA), Mendelian randomization (MR), differential expression analysis, and multivariate Cox analysis. A risk model was constructed and validated, with the High-Risk Group (HRG) and Low-Risk Group (LRG) defined by optimal risk score thresholds. Independent prognostic analysis, functional enrichment, immune infiltration profiling, and single-cell resolution studies were conducted to explore the underlying molecular mechanisms. Additionally, gene expression was validated in five paired clinical samples (5 tumor/5 normal tissues) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).</div></div><div><h3>Results</h3><div>HSDL2, AMACR, and CBR3 were identified as prognostic genes. The risk model indicated significantly poorer survival rates in HRG patients (P &lt; 0.05). It demonstrated strong predictive performance, with area under the curve (AUC) values exceeding 0.7 in both the training and validation sets. The risk score, tumor (T) stage, and lymph node (N) stage were identified as independent prognostic factors for a nomogram model (hazard ratio (HR ≠ 1, P &lt; 0.5). Pathways co-enriched by these markers, such as allograft rejection, were investigated. Immune infiltration analysis revealed significant differences between HRG and LRG in M0 macrophages and resting myeloid dendritic cells (mDCs) (P &lt; 0.5). Macrophages and epithelial/cancer cells were identified as key contributors to CC progression, exhibiting 13 and 7 distinct differentiation states, respectively, in pseudo-time analysis. Notably, HSDL2 and CBR3 expression levels were significantly different between normal and CC samples (P &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>HSDL2, AMACR, and CBR3 were established as prognostic biomarkers for CC. The risk model demonstrated robust predictive accuracy, offering a scientific foundation for clinical prognosis prediction in CC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114796"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312756","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":"KHSRP protects colorectal cancer cells against ferroptosis by regulating GPX4 expression through interaction with hnRNPM","authors":"Xia Ding ,&nbsp;Ningjing Zhang ,&nbsp;Shuai Zhan ,&nbsp;Wanjing Ding","doi":"10.1016/j.yexcr.2025.114812","DOIUrl":"10.1016/j.yexcr.2025.114812","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent form of programmed cell death driven by the accumulation of lipid peroxides. KHSRP, an RNA-binding protein, is known to orchestrate diverse cellular processes, including cell differentiation, proliferation, and lipid metabolism. However, its potential role in modulating ferroptosis in cancer remains unclear. In this study, we found that elevated KHSRP expression was associated with poor prognosis in colorectal cancer (CRC) patients. Knockdown of KHSRP significantly elevated lipid peroxidation, increased malondialdehyde (MDA) accumulation, and reduced glutathione (GSH) levels, ultimately triggering ferroptosis in CRC cells. Mechanistically, we discovered that KHSRP interacts with the splicing factor hnRNPM, which directly binds to GPX4 mRNA. Critically, hnRNPM overexpression effectively rescued the decrease in GPX4 expression and the ferroptotic phenotype induced by KHSRP knockdown. These results suggest that the KHSRP-hnRNPM complex binds to GPX4 mRNA and acts as a key regulator of its post-transcriptional fate to sustain GPX4 expression. Overall, our results uncover a novel regulatory mechanism whereby high KHSRP expression protects CRC cells from ferroptosis. Targeting the KHSRP–hnRNPM-GPX4 axis to overcome ferroptosis resistance represents a promising therapeutic strategy for CRC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114812"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426534","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}