Oncogene最新文献_第5页

Vimentin intermediate filaments orchestrate DNA nonhomologous end joining repair and lipolysis after DNA damage. 蛋白中间丝在DNA损伤后协调DNA非同源末端连接修复和脂解。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-23 DOI: 10.1038/s41388-025-03465-2

Feifei Wang, Mengtao Rong, Liang Zhang, Abhishikt D Solomon, Wenli Gui, Juan Li, Renqing Wang, Jiajing Wu, Ling Wang, Xingyuan Yang, Aimin Peng

{"title":"Vimentin intermediate filaments orchestrate DNA nonhomologous end joining repair and lipolysis after DNA damage.","authors":"Feifei Wang, Mengtao Rong, Liang Zhang, Abhishikt D Solomon, Wenli Gui, Juan Li, Renqing Wang, Jiajing Wu, Ling Wang, Xingyuan Yang, Aimin Peng","doi":"10.1038/s41388-025-03465-2","DOIUrl":"https://doi.org/10.1038/s41388-025-03465-2","url":null,"abstract":"Vimentin is a major component of intermediate filaments (IFs) within the three cytoskeletal systems, alongside actin filaments and microtubules. Spanning from the plasma membrane to the nuclear lamina, vimentin IFs form a cage-like network surrounding the nucleus, and modulate cell mechanics, migration and signaling. In this study, we show that vimentin depletion leads to accumulation of endogenous DNA damage. Interestingly, vimentin is associated with Ku proteins that sense DNA double strand breaks (DSB) and mediate nonhomologous end joining (NHEJ) repair. Depletion of vimentin impairs NHEJ repair, in line with reduced recruitment of Ku proteins to DNA damage sites and deficient activation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Beyond its involvement in DSB repair, our research also uncovers the role of vimentin in modulating lipolysis following DNA damage. We show that DNA damage reduces lipid droplet contents via adipose triglyceride lipase (ATGL). Vimentin binds to and suppresses ATGL in lipolysis. Moreover, DNA-PKcs modulates ATGL and DNA damage-induced lipolysis via vimentin. Targeting vimentin leads to DNA damage hypersensitivity, suggesting its potential in cancer therapy. Taken together, our findings elucidate new roles of vimentin in orchestrating DNA repair and lipolysis, shedding light on the involvement of vimentin IF in cell homeostasis, cancer resistance, and metabolic regulation.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: An FGFR-p53 developmental signaling axis drives salivary cancer progression. 更正：FGFR-p53发育信号轴驱动唾液癌进展。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-20 DOI: 10.1038/s41388-025-03478-x

Adele M Musicant, Julia M R Billington, Jeffrey S Damrauer, Jennifer L Modliszewski, Luane J B Landau, Yi-Hsuan Tsai, Jay H Mehta, John Powers, Renee Betancourt, Radhika Sekhri, Ricardo J Padilla, Juan C Hernandez-Prera, D Neil Hayes, Trevor G Hackman, Omer Gokcumen, Sarah M Knox, Antonio L Amelio

引用次数: 0

Correction: Emerging roles of cohesin-STAG2 in cancer 更正：黏结素- stag2在癌症中的新作用。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-20 DOI: 10.1038/s41388-025-03479-w

Julia S. Scott, Loubna Al Ayadi, Emmanouela Epeslidou, Roan H. van Scheppingen, Anna Mukha, Lucas J. T. Kaaij, Catrin Lutz, Stefan Prekovic

引用次数: 0

K88 acetylation of FTO increases its RNA m⁶A demethylation and promotes tumorigenesis. FTO的K88乙酰化增加其RNA m6A去甲基化，促进肿瘤发生。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-19 DOI: 10.1038/s41388-025-03473-2

Jing Li, Xinxin Zhang, Si-Yi Zhao, Ling Ran, Minmin Zhang, Shan Xie, Huifang Zhu, Guang-Rong Yan

{"title":"K88 acetylation of FTO increases its RNA m6A demethylation and promotes tumorigenesis.","authors":"Jing Li, Xinxin Zhang, Si-Yi Zhao, Ling Ran, Minmin Zhang, Shan Xie, Huifang Zhu, Guang-Rong Yan","doi":"10.1038/s41388-025-03473-2","DOIUrl":"10.1038/s41388-025-03473-2","url":null,"abstract":"N6-Methyladenosine (m6A) is the most abundant modification in mRNAs and regulates RNA splicing, stabilization, translation and export. FTO was the first discovered RNA m6A demethylase, and it is frequently dysregulated in cancers and plays important roles in tumorigenesis, cancer cell stemness, immune evasion, metabolic programs and drug resistance. Here, we report that FTO is acetylated at lysine 88 (K88) by the acetyltransferase GCN5 in vivo and in vitro. K88 acetylation significantly increases the RNA m6A demethylase activity of FTO. Acetylation of FTO at K88 has no effect on its stability, localization or dimerization but significantly increases its binding to m6A-modified RNA, thereby facilitating the removal of m6A from RNA. K88 acetylation is markedly increased in cancers, and the elimination of K88 acetylation in FTO inhibits the ability of FTO to stimulate tumorigenesis. K88 acetylation facilitates a reduction in the m6A level of FTO target mRNAs MYC, PDGFC, SOX10, CXCR4, NRF2, PLD1 and CDC42 and subsequently alters the stability or translation of these target mRNAs, thereby promoting tumorigenesis. Hence, K88 acetylation is critical for the RNA m6A demethylase activity and tumor-promoting functions of FTO.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MARCH1, transcriptionally regulated by POU2F2, facilitates acute myeloid leukemia progression via inducing MYCT1 degradation. 由POU2F2转录调控的MARCH1通过诱导MYCT1降解促进急性髓系白血病的进展。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-18 DOI: 10.1038/s41388-025-03464-3

Jianing Liu, Jianan Xu, Rongcan Sun, Xiaohui Wang, Fang Chen, Yu Fu, Henan Zhang, Bin Wu, Ying Yang, Jihong Zhang, Shuang Fu

{"title":"MARCH1, transcriptionally regulated by POU2F2, facilitates acute myeloid leukemia progression via inducing MYCT1 degradation.","authors":"Jianing Liu, Jianan Xu, Rongcan Sun, Xiaohui Wang, Fang Chen, Yu Fu, Henan Zhang, Bin Wu, Ying Yang, Jihong Zhang, Shuang Fu","doi":"10.1038/s41388-025-03464-3","DOIUrl":"https://doi.org/10.1038/s41388-025-03464-3","url":null,"abstract":"Acute myeloid leukemia (AML) is a heterogeneous clonal disease. Membrane-associated ring-CH type finger 1 (MARCH1), a membrane-anchored E3 ubiquitin ligase, is highly expressed in AML. However, its role in AML remains unclear. Our study showed that MARCH1 expression was strongly associated with FAB classifications and the survival of patients with AML. Gain-of-function and loss-of-function experiments showed that MARCH1 promoted the proliferation of AML cells and inhibited apoptosis and differentiation. In vivo, MARCH1 knockdown inhibited the infiltration of AML cells, resulting in prolonged survival of AML mice. In order to illustrate what cause the high expression of MARCH1, we analyzed the promoter region of MARCH1 and found that POU2F2, a transcription factor with high levels in AML, positively regulated the transcription of MARCH1. Finally, we demonstrated that MARCH1 interacted with MYCT1, a candidate tumor suppressor, and accelerated its ubiquitination and degradation. Remarkably, MYCT1 knockdown abolished the inhibitory effects of MARCH1 knockdown on AML cell growth. Our findings indicate that MARCH1, whose transcription is positively modulated by POU2F2, facilitates the malignant behaviors of AML cells through interacting with MYCT1 and accelerating its ubiquitination and degradation. The results implied that targeting MARCH1 might be a promising therapeutic strategy for AML.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PTEN neddylation aggravates CDK4/6 inhibitor resistance in breast cancer. PTEN类化修饰加重乳腺癌中CDK4/6抑制剂的耐药性。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-18 DOI: 10.1038/s41388-025-03468-z

Fan Liu, Weixiao Liu, Yawen Tan, Yaxin Shang, Sihui Ling, Xiaokun Jiang, Zhen Zhang, Shiyao Sun, Ping Xie

{"title":"PTEN neddylation aggravates CDK4/6 inhibitor resistance in breast cancer.","authors":"Fan Liu, Weixiao Liu, Yawen Tan, Yaxin Shang, Sihui Ling, Xiaokun Jiang, Zhen Zhang, Shiyao Sun, Ping Xie","doi":"10.1038/s41388-025-03468-z","DOIUrl":"https://doi.org/10.1038/s41388-025-03468-z","url":null,"abstract":"The gradual emergence of a novel therapeutic approach lies in the restoration of tumor suppressive machinery. PTEN is a crucial negative regulator of the PI3K/Akt signaling pathway. Protein neddylation modification contributes to PTEN inactivation and fuels breast cancer progression. Here, we highlight that an elevated level of PTEN neddylation is markedly associated with resistance to palbociclib, a CDK4/6 inhibitor used in luminal subtype breast cancer patients. Mechanistically, PTEN neddylation activates the PI3K/Akt signaling pathway, and more notably, upregulates the activity of the AP-1 transcription factor. Our data showed that PTEN neddylation stabilizes JUND, a transcription factor involved in the AP-1 complex, by disrupting its interaction with the E3 ubiquitin ligase ITCH. Consequently, activated JUND leads to the release of cytokines and chemokines, which in turn may drive an inflammatory tumor microenvironment, potentially contributing to drug resistance. Then, we identified Echinacoside as a potent inhibitor of PTEN neddylation both in vivo and in vitro by disrupting its interaction with XIAP, the E3 ligase responsible for PTEN neddylation. Combination of Echinacoside effectively overcome resistance to palbociclib in breast cancer treatment. These findings highlight targeting PTEN neddylation as a promising strategy for restoring tumor suppressor activity and overcoming resistance.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NNMT-mediated N⁶-methyladenosine modification of NR4A3 mRNA facilitates lymphatic metastasis of gastric adenocarcinoma. nnmt介导的NR4A3 mRNA的n6 -甲基腺苷修饰促进胃腺癌的淋巴转移。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-16 DOI: 10.1038/s41388-025-03475-0

Xiaoya Zhao, Linsen Bao, Yun Qian, Shimeng Zhou, Chen Chen, Zhuang Ma, Jiawen Xu, Mengmeng Li, Wenlu Niu, Bo Wang, Qiang Wang, Zhangding Wang, Shouyu Wang, Meng Wang

{"title":"NNMT-mediated N6-methyladenosine modification of NR4A3 mRNA facilitates lymphatic metastasis of gastric adenocarcinoma.","authors":"Xiaoya Zhao, Linsen Bao, Yun Qian, Shimeng Zhou, Chen Chen, Zhuang Ma, Jiawen Xu, Mengmeng Li, Wenlu Niu, Bo Wang, Qiang Wang, Zhangding Wang, Shouyu Wang, Meng Wang","doi":"10.1038/s41388-025-03475-0","DOIUrl":"https://doi.org/10.1038/s41388-025-03475-0","url":null,"abstract":"Lymph node (LN) metastasis is a common feature of gastric adenocarcinoma (GAC) and is closely associated with a poor prognosis. Our previous study highlighted the pivotal role of nicotinamide N-methyltransferase (NNMT) in driving GAC carcinogenesis and malignant progression, primarily through its regulation of histone methylation. However, the mechanisms by which NNMT contributes to LN metastasis in GAC remain poorly understood. In this study, we demonstrated that elevated NNMT expression was positively correlated with LN metastasis and a poor prognosis in GAC patients. Gain- and loss-of-function experiments further revealed that NNMT accelerated GAC-related lymphangiogenesis, migration, and invasion in vitro and facilitated LN metastasis in vivo. Mechanistically, NNMT promoted the degradation of NR4A3 mRNA by diminishing its m6A methylation, which diminished the binding of NR4A3 protein to the promoters of fibroblast growth factor 2 (FGF2) and hepatocyte growth factor (HGF), leading to increased expression of FGF2 and HGF, which in turn enhanced lymphangiogenesis and facilitated lymphatic metastasis in GAC. Collectively, our findings suggest that NNMT plays an oncogenic role in GAC and may serve as a valuable prognostic biomarker and therapeutic target for treating LN-metastatic GAC. NNMT promotes NR4A3 mRNA degradation by diminishing its m6A methylation, consequently promoting lymphangiogenesis and lymphatic metastasis in GAC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting TFAM downregulation mediated mtDNA-NLRP3 pathway suppresses TAM infiltration and HCC progression. 靶向TFAM下调介导的mtDNA-NLRP3通路抑制TAM浸润和HCC进展。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-14 DOI: 10.1038/s41388-025-03467-0

Jing Zhao, Mengmeng Cui, Xiaojuan Yao, Zhixiong Jiang, Lixia Qi, Jiaxing Chen, Chunhui Fan, Shuwen Bai, Chengying Zhou, Rui Wei, Hongliang Liu, Qi Yang, Lixin Wan, Dengke Bao

{"title":"Targeting TFAM downregulation mediated mtDNA-NLRP3 pathway suppresses TAM infiltration and HCC progression.","authors":"Jing Zhao, Mengmeng Cui, Xiaojuan Yao, Zhixiong Jiang, Lixia Qi, Jiaxing Chen, Chunhui Fan, Shuwen Bai, Chengying Zhou, Rui Wei, Hongliang Liu, Qi Yang, Lixin Wan, Dengke Bao","doi":"10.1038/s41388-025-03467-0","DOIUrl":"https://doi.org/10.1038/s41388-025-03467-0","url":null,"abstract":"The infiltration of TAMs mediates an immunosuppressive tumor microenvironment, which plays a crucial role in the malignant progression of HCC. TFAM is a key molecule that regulates mtDNA replication and transcription, and its expression frequently downregulated in various tumors, including HCC. Our previous study indicated that the downregulation of TFAM triggers mtDNA stress, thereby inducing autophagy and promoting ESCC survival through the STING pathway. However, it remains unclear whether cytosolic mtDNA stress, mediated by TFAM downregulation, is implicated in microenvironment regulation, particularly in the infiltration of TAMs in HCC. In this study, we found that TFAM expression was significantly decreased and correlated with CD163 expression in HCC tissues. The downregulated expression of TFAM in HCC cells contributed to TAM infiltration. Mechanistically, the downregulation of TFAM induced cytosolic mtDNA stress, which activated the NLRP3 inflammasome and promoted the expression of IL-18 and IL-1β in HCC cells, thereby inducing macrophage recruitment and M2 polarization. Depleting cytosolic mtDNA using DNase I or blocking NLRP3 inflammasome activation with an NLRP3 antagonist in HCC cells with TFAM downregulation significantly suppresses the infiltration of M2-TAMs. Moreover, blocking the mtDNA-NLRP3 pathway significantly inhibited TAM infiltration and orthotopic mouse HCC model progression. Taken together, our results reveal a novel mechanism by which cytosolic mtDNA stress mediates TAM infiltration in HCC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

REPS2 attenuates cancer stemness through inhibiting Wnt signaling by autophagy mediated degradation of β-catenin. REPS2通过自噬介导的β-catenin降解抑制Wnt信号传导，从而减弱癌症的干性。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-13 DOI: 10.1038/s41388-025-03469-y

Lu Liu, Shuzhen Chen, Yuxi Lei, Zejian Lin, Rulan Zhou, Guandi Zeng, Zongyao Zheng, Wanting Liu, Qian Zhou, Liang Chen

引用次数: 0

Correction: Repression of microRNA-768-3p by MEK/ERK signalling contributes to enhanced mRNA translation in human melanoma 更正：MEK/ERK信号抑制microRNA-768-3p有助于增强人类黑色素瘤的mRNA翻译。

IF 6.9 1区医学

Oncogene Pub Date : 2025-06-10 DOI: 10.1038/s41388-025-03442-9

C. C. Jiang, A. Croft, H. -Y. Tseng, S. T. Guo, L. Jin, P. Hersey, X. D. Zhang

引用次数: 0