Cell Death & Disease最新文献_第5页

Atypical contribution of caspase-3 to melanoma cancer cell motility by regulation of coronin 1B activity. caspase-3通过调节冠状蛋白1B活性对黑色素瘤癌细胞运动的非典型贡献。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-10-06 DOI: 10.1038/s41419-025-07952-y

Kevin Berthenet, Serena Diazzi, Catherine Jamard, Kinga B Stopa, Clara Gil, Stefan Dragan, Deborah Fanfone, Trang Tm Nguyen, Nathalie Al, Francois Virard, Olivier Meurette, Nikolay Popgeorgiev, Hector Hernandez-Vargas, Julien Ablain, Gabriel Ichim

{"title":"Atypical contribution of caspase-3 to melanoma cancer cell motility by regulation of coronin 1B activity.","authors":"Kevin Berthenet, Serena Diazzi, Catherine Jamard, Kinga B Stopa, Clara Gil, Stefan Dragan, Deborah Fanfone, Trang Tm Nguyen, Nathalie Al, Francois Virard, Olivier Meurette, Nikolay Popgeorgiev, Hector Hernandez-Vargas, Julien Ablain, Gabriel Ichim","doi":"10.1038/s41419-025-07952-y","DOIUrl":"10.1038/s41419-025-07952-y","url":null,"abstract":"Recent studies have unveiled unexpected connections between cell death and cell motility. While traditionally recognized for their pro-apoptotic roles, caspases have emerged as regulators of physiological processes beyond cell death, including cellular differentiation and motility. In some particularly aggressive cancers like melanoma, caspase-3, a prominent executioner caspase, is unexpectedly and inexplicably highly expressed. Here, we describe a novel non-apoptotic role for caspase-3 in melanoma cell motility. Through comprehensive molecular and cellular analyses, we demonstrate that caspase-3 is constitutively associated with the cytoskeleton and crucially regulates melanoma cell migration and invasion in vitro and in vivo. Mechanistically, caspase-3 interacts with and modulates the activity of coronin 1B, a key regulator of actin polymerization, thereby promoting melanoma cell motility, independently of its apoptotic protease function. Furthermore, we identify specificity protein 1 (SP1) as a transcriptional regulator of CASP3 expression, and show that its inhibition reduces caspase-3 expression and impairs melanoma cell migration. Overall, this study provides insights into the multifaceted roles of caspase-3 in cancer progression, highlighting its relevance as a novel target for anti-metastatic therapies.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"690"},"PeriodicalIF":9.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MEK5/ERK5 inhibition sensitizes NRAS-mutant melanoma to MAPK-targeted therapy by preventing Cyclin D/CDK4-mediated G1/S progression. MEK5/ERK5抑制通过阻止Cyclin D/ cdk4介导的G1/S进展使nras突变黑色素瘤对mapk靶向治疗增敏。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-10-06 DOI: 10.1038/s41419-025-08036-7

Rupesh Paudel, Simon Goller, Felix Deutzmann, Alina Gillitzer, Katharina Meder, Andrea Knorz, David Schrama, Matthias Goebeler, Marc Schmidt

{"title":"MEK5/ERK5 inhibition sensitizes NRAS-mutant melanoma to MAPK-targeted therapy by preventing Cyclin D/CDK4-mediated G1/S progression.","authors":"Rupesh Paudel, Simon Goller, Felix Deutzmann, Alina Gillitzer, Katharina Meder, Andrea Knorz, David Schrama, Matthias Goebeler, Marc Schmidt","doi":"10.1038/s41419-025-08036-7","DOIUrl":"10.1038/s41419-025-08036-7","url":null,"abstract":"Despite the advent of immune-oncological therapies, patients with advanced NRAS-mutant melanoma still have a significantly worse prognosis than their BRAF-mutant counterparts. This is mainly due to a high propensity for resistance to available therapies targeting the RAS/RAF/MEK/ERK mitogen-activated protein kinase (MAPK) pathway (MAPKi). Preclinical studies and mouse models have implicated the stress-activated MEK5/ERK5 MAPK cascade as a major resistance pathway activated by MAPKi-based targeted therapy in NRAS-mutant melanoma. Accordingly, MAPKi/ERK5i co-inhibition was capable of triggering a sustained cell cycle arrest in NRAS-mutant melanoma cells, but the key mediator(s) of its vigorous anti-proliferative effect remain elusive. Here, we further investigated the mechanism of MAPKi/ERK5i-induced cell cycle arrest in NRAS-mutant melanoma cells using both genetic methods and pharmacological inhibitors. Transcriptome analysis of human NRAS-mutant melanoma cells established that MAPKi/ERK5iinduced a near-complete shutdown of the mitotic machinery as consequence of a sustained G1 cell cycle arrest. This arrest was not only observed in diverse treatment-naïve melanoma cells but could also be induced in cells that already had developed resistance to therapeutic MEK inhibition (MEKi) and was accompanied by suppression of Cyclin D1 and E2F-mediated gene expression. Forced expression of Cyclin D1 and its effector kinase CDK4 restored cell cycle progression and mitotic gene expression in NRAS-mutant melanoma cells exposed to MEKi/ERK5i, implying Cyclin D/CDK4 activity as major target of combined MEKi/ERK5i. These findings suggest Cyclin D/CDK4 dependency as a major vulnerability of NRAS-mutant melanoma that could effectively be targeted by combined MAPKi/ERK5i.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"689"},"PeriodicalIF":9.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactate-mediated histone lactylation promotes melanoma angiogenesis via IL-33/ST2 axis. 乳酸介导的组蛋白乳酸化通过IL-33/ST2轴促进黑色素瘤血管生成。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-10-06 DOI: 10.1038/s41419-025-08023-y

Mao Zhao, Yuxuan Qian, Lin He, Taoxin Peng, Hanbin Wang, Xiangxu Wang, Linhan Jiang, Jinrong Fan, Hengxiang Zhang, Di Qu, Qing Zhu, Hao Wang, Shida Zhang, Chenyang Li, Xiwen Dong, Xianya Zhao, Huina Wang, Yuqi Yang, Xiuli Yi, Tao Zhao, Yu Liu, Jianglin Zhang, Guoqiang Zhang, Qiong Shi, Tianwen Gao, Chunying Li, Weinan Guo

{"title":"Lactate-mediated histone lactylation promotes melanoma angiogenesis via IL-33/ST2 axis.","authors":"Mao Zhao, Yuxuan Qian, Lin He, Taoxin Peng, Hanbin Wang, Xiangxu Wang, Linhan Jiang, Jinrong Fan, Hengxiang Zhang, Di Qu, Qing Zhu, Hao Wang, Shida Zhang, Chenyang Li, Xiwen Dong, Xianya Zhao, Huina Wang, Yuqi Yang, Xiuli Yi, Tao Zhao, Yu Liu, Jianglin Zhang, Guoqiang Zhang, Qiong Shi, Tianwen Gao, Chunying Li, Weinan Guo","doi":"10.1038/s41419-025-08023-y","DOIUrl":"10.1038/s41419-025-08023-y","url":null,"abstract":"The pathogenesis of cancer is complicated, with metabolic reprogramming and angiogenesis as the hallmark characteristics. Recent reports have unveiled that the glycolytic metabolite lactate could modify histone lactylation to epigenetically regulate gene expressions and biological processes in cancer, while the effect on tumor angiogenesis remains elusive. By taking advantage of melanoma as the model, we first proved that lactate and histone lactylation facilitated melanoma angiogenesis both in vitro and in vivo. Then, through RNA-sequencing and a series of biochemical assays, we found that lactate promoted the transcription of suppression of tumorigenicity 2 (ST2) in tumor-associated endothelial cells via the enhancement of histone lactylation at its promoter, so that to increase the response of endothelial cells to pro-angiogenic interleukin-33 (IL-33) stimulation. In addition, lactate could also suppress high endothelial venules transition of endothelial cells, which was critical for tumor development. Ultimately, the effect of anti-angiogenic drug synergized with lactate dehydrogenase (LDH) inhibition/ST2 inhibition on melanoma growth was proved in vivo. Taken together, we demonstrated that lactate-mediated histone lactylation promotes melanoma angiogenesis via IL-33/ST2 axis, which delineated a novel regulatory relationship among lactate, histone lactylation and angiogenesis in cancer, and provided a promising combined therapeutic strategy to target angiogenesis from the perspective of cell metabolism and epigenetics in cancer.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"701"},"PeriodicalIF":9.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung cancer cells upregulate stearoyl-CoA desaturase 1 in microglia by activating the STAT3 pathway to change microglial inflammatory response in lung-to-brain metastases. 肺癌细胞通过激活STAT3通路上调小胶质细胞中的硬脂酰辅酶a去饱和酶1，从而改变肺到脑转移的小胶质细胞炎症反应。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-10-06 DOI: 10.1038/s41419-025-08003-2

Peng Chen, Yufeng Zuo, Minghuan Wang, Rui Liu, Ying Li, Ziyue Wang, Hao Huang, Xiang Luo, Wei Wang, Yingying Wu, Zhiyuan Yu

{"title":"Lung cancer cells upregulate stearoyl-CoA desaturase 1 in microglia by activating the STAT3 pathway to change microglial inflammatory response in lung-to-brain metastases.","authors":"Peng Chen, Yufeng Zuo, Minghuan Wang, Rui Liu, Ying Li, Ziyue Wang, Hao Huang, Xiang Luo, Wei Wang, Yingying Wu, Zhiyuan Yu","doi":"10.1038/s41419-025-08003-2","DOIUrl":"10.1038/s41419-025-08003-2","url":null,"abstract":"Lung cancer brain metastases have been considered a terminal disease stage with limited treatment options. Many studies have shown that microglia as the resident macrophages in the brain form a major component of the brain immune system, and the lipid metabolism of macrophages in the tumor microenvironment could directly influence tumor progression. However, limited studies have explored the regulatory role of lipid metabolism on microglia in brain metastases. In this study, we found that lung cancer cells could promote microglia to express stearoyl-CoA desaturase 1 (SCD1) and accumulate lipid droplets. Increased activity of SCD1 in microglia reduced its response to inflammatory stimuli and promoted the proliferation of cancer cells. Notably, the treatment of tumor-bearing mice with an SCD1 inhibitor combined with an inhibitor of colony-stimulating factor 1 receptor (CSF1R) significantly reduced brain metastases. Mechanistically, we demonstrated that lung cancer cells activated the STAT3 signaling pathway in microglia leading to increased SCD1 expression. In conclusion, our findings indicate that lung cancer cells activate the microglial STAT3-SCD1-lipid metabolism-inflammatory response pathway in the brain tumor microenvironment and present a potential new strategy for treating brain metastases of lung cancer.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"702"},"PeriodicalIF":9.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer-associated fibroblasts expressing FSTL3 promote vasculogenic mimicry formation and drive colon cancer malignancy. 表达FSTL3的癌症相关成纤维细胞促进血管生成模拟形成并驱动结肠癌恶性肿瘤。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-10-06 DOI: 10.1038/s41419-025-08009-w

Leqian Ying, Yini Zhu, Lu Zhang, Min Ji, Meidan Wang, Lei Dong, Zhengcheng Yun, Yanping Chen, Jingyi Zhou, Chunchun Huang, Shengwei Zhang, Xuhong Yang, Hui Yang, Guichun Huang, Shukui Qin, Jinbing Xie, Lin Liu

{"title":"Cancer-associated fibroblasts expressing FSTL3 promote vasculogenic mimicry formation and drive colon cancer malignancy.","authors":"Leqian Ying, Yini Zhu, Lu Zhang, Min Ji, Meidan Wang, Lei Dong, Zhengcheng Yun, Yanping Chen, Jingyi Zhou, Chunchun Huang, Shengwei Zhang, Xuhong Yang, Hui Yang, Guichun Huang, Shukui Qin, Jinbing Xie, Lin Liu","doi":"10.1038/s41419-025-08009-w","DOIUrl":"10.1038/s41419-025-08009-w","url":null,"abstract":"Anti-angiogenic therapies are commonly employed in colon cancer management, yet many patients eventually develop resistance and experience disease progression. Vasculogenic mimicry (VM)-the formation of tumor-derived vessel-like networks-has been recognized as one mechanism contributing to this resistance, although the underlying details remain incompletely understood. Here, by integrating bioinformatic analyses of publicly available datasets and validating the results in patient samples (n = 157), we identified follistatin-like 3 (FSTL3) as a critical factor predominantly expressed in colon cancer-associated fibroblasts (CCAFs), with its expression strongly correlating with increased VM formation, intratumoral blood vessels, and poor prognosis. Single-cell RNA sequencing of tumors from VM and non-VM patients revealed that hypoxia drives FSTL3 expression in CCAFs, leading to extracellular matrix remodeling and enhancing cancer cell endothelial-like plasticity. Mechanistically, FSTL3 binds to transferrin receptor (TfR1), an iron-uptake receptor on cancer cells, thereby activating the TfR1/AKT/mTOR pathway and elevating VE-Cadherin to support endothelial-like transformation, VM, and metastatic progression. Notably, FSTL3-targeting antibodies (aFSTL3) effectively inhibited VM and angiogenesis in both in vitro and in vivo models, while the combination of aFSTL3 with bevacizumab produced synergistic suppression of neovascular-like structures and distant metastases. These findings demonstrate a pivotal role for FSTL3+ CCAFs in facilitating VM through TfR1-mediated signaling and offer a promising dual-target approach to overcome anti-angiogenic therapy resistance in colon cancer.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"706"},"PeriodicalIF":9.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: CUL1 promotes trophoblast cell invasion at the maternal-fetal interface. 更正：CUL1促进母胎界面滋养细胞侵袭。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-09-30 DOI: 10.1038/s41419-025-07994-2

Q Zhang, Q Chen, X Lu, Z Zhou, H Zhang, H-Y Lin, E Duan, C Zhu, Y Tan, H Wang

引用次数: 0

BAP31 represses endoplasmic reticulum stress-mediated apoptosis and alleviates neurodegeneration in Parkinson's disease. BAP31抑制内质网应激介导的细胞凋亡并缓解帕金森病的神经变性。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-09-29 DOI: 10.1038/s41419-025-07907-3

Yan Qin, Ying Chen, Minghao Chi, Junzhen Jia, Li Wang, Yan Zhao, Zhecheng Wang, Junjun Zhou, Jihong Yao

{"title":"BAP31 represses endoplasmic reticulum stress-mediated apoptosis and alleviates neurodegeneration in Parkinson's disease.","authors":"Yan Qin, Ying Chen, Minghao Chi, Junzhen Jia, Li Wang, Yan Zhao, Zhecheng Wang, Junjun Zhou, Jihong Yao","doi":"10.1038/s41419-025-07907-3","DOIUrl":"10.1038/s41419-025-07907-3","url":null,"abstract":"Excessive endoplasmic reticulum (ER) stress and neuronal apoptosis contribute to neurodegeneration in Parkinson's disease (PD). However, the molecular mechanisms underlying these perturbations and how they are directly regulated remain unclear. B cell receptor-associated protein 31 (BAP31), which is highly expressed in the ER, has been shown to participate mainly in regulating ER stress and apoptosis. Here, our results showed that BAP31 expression was dramatically decreased in PD. Notably, overexpression of BAP31 exerted neuroprotective effects by inhibiting ER stress and apoptosis in vitro and in vivo, whereas BAP31 siRNA strongly abolished these effects. Interestingly, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, reversed the detrimental effect of BAP31 knockdown in vitro. Mutations in PTEN-induced putative kinase 1 (PINK1) are known to cause autosomal recessive early-onset PD. PINK1 has been implicated in protein phosphorylation pathways that are associated with ER stress and apoptosis. Bioinformatics analysis and our results demonstrated that PINK1 interacts with BAP31 and phosphorylates it at the Ser 142 residue. Furthermore, the protective effects of PINK1 overexpression against ER stress-mediated apoptosis were abolished by BAP31 interference or BAP31-S142A and strengthened by BAP31-S142E. Overall, the present study suggests that BAP31 overexpression exerts neuroprotective effects by inhibiting ER stress-induced apoptosis. Regulation of the PINK1/BAP31 pathway may be a beneficial strategy for PD.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"672"},"PeriodicalIF":9.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TUFT1 regulates cancer progression by suppressing centrosome amplification and mitotic spindle multipolarity. TUFT1通过抑制中心体扩增和有丝分裂纺锤体多极性调节癌症进展。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-09-29 DOI: 10.1038/s41419-025-08010-3

Shaojie Feng, Mengmeng Zhao, Donghui Zhang, Yan Zhang, Lingyuan Min, Xianqiang Liu, Huan Shi, Tianning Wang

{"title":"TUFT1 regulates cancer progression by suppressing centrosome amplification and mitotic spindle multipolarity.","authors":"Shaojie Feng, Mengmeng Zhao, Donghui Zhang, Yan Zhang, Lingyuan Min, Xianqiang Liu, Huan Shi, Tianning Wang","doi":"10.1038/s41419-025-08010-3","DOIUrl":"10.1038/s41419-025-08010-3","url":null,"abstract":"Centrosome amplification (CA) has been observed in various solid tumors and contributes to chromosomal instability (CIN) and poor clinical prognosis in patients with cancer. CA also inhibits cell proliferation by inducing cell-cycle arrest and cell death. However, the mechanism of regulation of centrosome number in cancer cells and its effect on CIN and cell proliferation remains elusive. Here, we report that tuftelin (TUFT1) is a novel centrosomal protein that localizes to the proximal ends of parent centrioles. TUFT1 prevents CA and mitotic spindle multipolarity by suppressing premature polo-like kinase 1 activation. In addition, TUFT1 is phosphorylated by NIMA-related kinase 2 (NEK2), and the phosphorylation status of TUFT1 is essential for coordinating centrosome number and cell proliferation in cervical and breast cancers. Data from clinical breast cancer samples indicate that the combined detection of TUFT1 and NEK2 expression reflects tumor malignancy and patient survival with higher precision. Overall, these results reveal a crucial role of TUFT1 in the regulation of tumor progression through centrosome number control. Thus, TUFT1 represents a promising target for diagnostic and therapeutic approaches for cancers.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"673"},"PeriodicalIF":9.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction Note: Downregulation of the Rho GTPase pathway abrogates resistance to ionizing radiation in wild-type p53 glioblastoma by suppressing DNA repair mechanisms. 注：Rho GTPase通路下调通过抑制DNA修复机制消除野生型p53胶质母细胞瘤对电离辐射的抗性。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-09-23 DOI: 10.1038/s41419-025-08071-4

Yuli Thamires Magalhaes, Viktor Kalbermatter Boell, Giovanna Duo Cardella, Fabio Luis Forti

引用次数: 0

CircPSD3 aggravates tumor progression by maintaining TCA cycle and mitochondrial function via regulating SUCLG2 in thyroid carcinoma. 在甲状腺癌中，CircPSD3通过调节SUCLG2来维持TCA循环和线粒体功能，从而加剧肿瘤进展。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-09-09 DOI: 10.1038/s41419-025-07856-x

Yijia Sun, Beinan Han, Jiawei Ge, Zijun Huo, Jin Li, Bo Lin, Xin Du, Yimin Zhang, Haiyan Weng, Shuang Yu, Yanbing Li, Haipeng Xiao, Xiaorong Lin, Shubin Hong

{"title":"CircPSD3 aggravates tumor progression by maintaining TCA cycle and mitochondrial function via regulating SUCLG2 in thyroid carcinoma.","authors":"Yijia Sun, Beinan Han, Jiawei Ge, Zijun Huo, Jin Li, Bo Lin, Xin Du, Yimin Zhang, Haiyan Weng, Shuang Yu, Yanbing Li, Haipeng Xiao, Xiaorong Lin, Shubin Hong","doi":"10.1038/s41419-025-07856-x","DOIUrl":"10.1038/s41419-025-07856-x","url":null,"abstract":"In recent years, there has been a rapid increase in the incidence of thyroid carcinoma (TC). Our study focuses on the regulatory effect of circular RNAs on metabolism of TC, aiming to provide new insights into the mechanisms of progression and a potential therapeutic target for TC. In this study, we identified high expression levels of circPSD3 in TC tissues through RNA sequencing. Papillary thyroid cancer tissue cohorts verified the circPSD3 expression level was positively correlated with larger tumor size. circPSD3 promoted the proliferation of TC cells and reduced apoptosis both in vitro and in vivo. Proteomics and metabolomics suggested that circPSD3 might play a crucial role in regulating the tricarboxylic acid (TCA) cycle. Specifically, circPSD3 acted as a miR-338-5p sponge to upregulate SUCLG2, an enzyme of the TCA cycle, which accelerates the conversion of α-ketoglutarate (α-KG) to succinate. Knockdown of circPSD3 disrupts the TCA cycle and impairs mitochondrial function, resulting in decreased membrane potential and aerobic respiration rate. The reduction in mitochondrial function resulted in the inhibition of proliferation and initiation of mitochondria-mediated apoptosis.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"590"},"PeriodicalIF":9.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0