Oncogene最新文献_第7页

The splicing factor SRRM2 modulates two S6K kinases to promote colorectal cancer growth.

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-16 DOI: 10.1038/s41388-025-03307-1

Zhengwei Yan, Luling He, Jiawei Yuan, Yulong Niu, Shimin Shuai, Shiwen Luo, Changzheng Du, Hai Rao

引用次数: 0

SUMOylation inhibition potentiates the glucocorticoid receptor to program growth arrest of acute lymphoblastic leukemia cells.

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-14 DOI: 10.1038/s41388-025-03305-3

Emma Valima, Vera Varis, Kseniia Bureiko, Joanna K Lempiäinen, Anna-Mari Schroderus, Laura Oksa, Olli Lohi, Tuure Kinnunen, Markku Varjosalo, Einari A Niskanen, Ville Paakinaho, Jorma J Palvimo

{"title":"SUMOylation inhibition potentiates the glucocorticoid receptor to program growth arrest of acute lymphoblastic leukemia cells.","authors":"Emma Valima, Vera Varis, Kseniia Bureiko, Joanna K Lempiäinen, Anna-Mari Schroderus, Laura Oksa, Olli Lohi, Tuure Kinnunen, Markku Varjosalo, Einari A Niskanen, Ville Paakinaho, Jorma J Palvimo","doi":"10.1038/s41388-025-03305-3","DOIUrl":"https://doi.org/10.1038/s41388-025-03305-3","url":null,"abstract":"Glucocorticoids are a mainstay in the treatment of B-cell acute lymphoblastic leukemia (B-ALL). The glucocorticoid receptor (GR), a ligand-activated transcription factor (TF), mediates their actions. Chromatin occupancy, chromatin-protein networks (chromatomes) and gene programmes of GR are regulated by SUMOylation, a post-translational modification with therapeutic implications in other hematomalignancies. To unravel the GR-SUMOylation crosstalk in B-ALL, we induced hypoSUMOylation in NALM6 B-ALL cells with a SUMOylation inhibitor (SUMOi, ML-792). Genome-wide profiling of GR and SUMO chromatin-binding and chromatin accessibility revealed that hypoSUMOylation augmented GR chromatin occupancy and altered chromatin openness. Association with transcriptome data indicated that the hypoSUMOylation-induced GR-binding sites predominantly repressed genes associated with cell cycle and DNA replication. Consistently, hypoSUMOylation potentiated glucocorticoid-induced cell cycle arrest and growth suppression. Moreover, our proteomic analyses revealed that the protein network of chromatin-bound GR is tightly intertwined with SUMO2/3 and that SUMOylation modulates the stability of the network. The chromatome contained several B-cell TFs with cognate binding motifs found on GR-adjacent chromatin sites, indicating their simultaneous occupancy on chromatin. In sum, our data imply potential for targeting SUMOylation to increase sensitivity to glucocorticoids in B-ALL, supported by ex vivo data of glucocorticoid and SUMOi TAK-981 combination-treated B-ALL patient samples.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425475","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

PPP2R1A mutations cause ATR inhibitor sensitivity in ovarian clear cell carcinoma

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-12 DOI: 10.1038/s41388-024-03265-0

James Stewart, Dragomir B. Krastev, Rachel Brough, Diana Zatreanu, Feifei Song, Joseph S. Baxter, Sandhya Sridhar, Jessica Frankum, Asha Konde, William Yang, Syed Haider, John Alexander, Kai Betteridge, Aditi Gulati, Ayoma D. Attygalle, Katherine Vroobel, Rachael Natrajan, Saira Khalique, Theodoros I. Roumeliotis, Jyoti S. Choudhary, Jason Yeung, Andrew J. Wicks, Rebecca Marlow, Susana Banerjee, Stephen J. Pettitt, Andrew N. J. Tutt, Christopher J. Lord

{"title":"PPP2R1A mutations cause ATR inhibitor sensitivity in ovarian clear cell carcinoma","authors":"James Stewart, Dragomir B. Krastev, Rachel Brough, Diana Zatreanu, Feifei Song, Joseph S. Baxter, Sandhya Sridhar, Jessica Frankum, Asha Konde, William Yang, Syed Haider, John Alexander, Kai Betteridge, Aditi Gulati, Ayoma D. Attygalle, Katherine Vroobel, Rachael Natrajan, Saira Khalique, Theodoros I. Roumeliotis, Jyoti S. Choudhary, Jason Yeung, Andrew J. Wicks, Rebecca Marlow, Susana Banerjee, Stephen J. Pettitt, Andrew N. J. Tutt, Christopher J. Lord","doi":"10.1038/s41388-024-03265-0","DOIUrl":"10.1038/s41388-024-03265-0","url":null,"abstract":"Identification of ARID1A/ATR synthetic lethality led to ATR inhibitor phase II trials in ovarian clear cell carcinoma (OCCC), a cancer of unmet need. Using multiple CRISPR-Cas9 mutagenesis and interference screens, we show that inactivation of protein phosphatase 2A (PP2A) subunits, including PPP2R1A, enhance ATRi sensitivity in ARID1A mutant OCCC. Analysis of a new OCCC cohort indicates that 52% possess oncogenic PPP2R1A p.R183 mutations and of these, one half possessed both ARID1A as well as PPP2R1A mutations. Using CRISPR-prime editing to generate new isogenic models of PPP2R1A mutant OCCC, we found that PPP2R1A p.R183W and p.R183P mutations cause ATRi-induced S phase stress, premature mitotic entry, genomic instability and ATRi sensitivity in OCCC tumour cells. p.R183 mutation also enhanced both in vitro and in vivo ATRi sensitivity in preclinical models of ARID1A mutant OCCC. These results argue for the assessment of PPP2R1A mutations as a biomarker of ATRi sensitivity.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 9","pages":"618-629"},"PeriodicalIF":6.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03265-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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: A novel amplification gene PCI domain containing 2 (PCID2) promotes colorectal cancer through directly degrading a tumor suppressor promyelocytic leukemia (PML)

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-12 DOI: 10.1038/s41388-025-03304-4

Jingwan Zhang, Jianning Zhai, Chi Chun Wong, Huarong Chen, Xiaohong Wang, Jiafu Ji, Jun Yu

引用次数: 0

Helicobacter pylori activates DOPEY1 to promote p53 degradation through the USP7/TRIP12 axis in gastric tumorigenesis.

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-12 DOI: 10.1038/s41388-025-03303-5

Yan-An Zhou, Nian-Shuang Li, Yu-Chen Zhu, Ze-Kun He, Yaobin Ouyang, Li-Xiang Ling, Xi-Dong Wu, Hui-Qiao Zhou, Huan Wang, Xin-Bo Xu, Xiao Fei, Cong He, Yu-Juan Dong, Jianping Liu, Nong-Hua Lu, Yin Zhu, Yi Hu

{"title":"Helicobacter pylori activates DOPEY1 to promote p53 degradation through the USP7/TRIP12 axis in gastric tumorigenesis.","authors":"Yan-An Zhou, Nian-Shuang Li, Yu-Chen Zhu, Ze-Kun He, Yaobin Ouyang, Li-Xiang Ling, Xi-Dong Wu, Hui-Qiao Zhou, Huan Wang, Xin-Bo Xu, Xiao Fei, Cong He, Yu-Juan Dong, Jianping Liu, Nong-Hua Lu, Yin Zhu, Yi Hu","doi":"10.1038/s41388-025-03303-5","DOIUrl":"https://doi.org/10.1038/s41388-025-03303-5","url":null,"abstract":"DOP1 leucine zipper-like protein A (DOPEY1), a member of the DOPEY family, is mainly localized in the Golgi apparatus, endosomes, and cytoplasmic compartments within cells. The involvement of DOPEY1 in H. pylori infection-induced carcinogenesis has remained unresolved. Here, we report that DOPEY1 is upregulated in GC tissues compared to adjacent normal tissues, correlating with poor prognosis. Mechanistically, H. pylori infection increases DOPEY1 expression and promotes p53 degradation through a CagA-dependent pathway. Using the String database and liquid chromatography-mass spectrometry, we identified DOPEY1-interacting proteins, confirming through co-immunoprecipitation that DOPEY1 interacts with USP7 and TRIP12. H. pylori infection enhances the expression of DOPEY1, USP7, and TRIP12, leading to p53 degradation, which is reversed by DOPEY1 silencing. Moreover, USP7 overexpression rescues p53 degradation in DOPEY1-silenced cells. Functionally, DOPEY1 knockdown reduces GC cell proliferation and suppresses tumor growth in mouse models. Immunohistochemistry analysis further reveals a link between DOPEY1, USP7, and TRIP12 expression, H. pylori infection, and GC progression. These findings demonstrate that H. pylori-induced upregulation of DOPEY1 drives p53 degradation via the USP7/TRIP12 axis, contributing to gastric tumorigenesis, and highlight DOPEY1 as a potential therapeutic target for H. pylori-associated GC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408467","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: Potential role for Cathepsin D in p53-dependent tumor suppression and chemosensitivity

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-11 DOI: 10.1038/s41388-025-03291-6

Gen Sheng Wu, Paul Saftig, Christoph Peters, Wafik S. El-Deiry

引用次数: 0

circAFF2 promotes the development of AML by binding to PML mRNA.

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-10 DOI: 10.1038/s41388-025-03299-y

Lei Yao, Xinyang Zhang, Xiaoqing Li, Jin Xu, Siqi Yang, Fengyue Li, Wenbo Chen, Yuxin Shan, Linli Ren, Chenjian Zhuo, Sisi Liang, Lu Chen, Weinan Yin, Hudan Liu, Lingbo Liu, Mingqian Feng, Ke Chen, Shuliang Chen, Chunjiang He

{"title":"circAFF2 promotes the development of AML by binding to PML mRNA.","authors":"Lei Yao, Xinyang Zhang, Xiaoqing Li, Jin Xu, Siqi Yang, Fengyue Li, Wenbo Chen, Yuxin Shan, Linli Ren, Chenjian Zhuo, Sisi Liang, Lu Chen, Weinan Yin, Hudan Liu, Lingbo Liu, Mingqian Feng, Ke Chen, Shuliang Chen, Chunjiang He","doi":"10.1038/s41388-025-03299-y","DOIUrl":"https://doi.org/10.1038/s41388-025-03299-y","url":null,"abstract":"AML is a complex disease caused by multiple molecular mechanisms. As an important regulatory molecule, the role of circRNA in AML is not fully understood. By performing high-throughput sequencing on clinical samples, we systematically identified the differences in circRNA expression and distribution between AML and healthy donor samples. One circular RNA, circAFF2, was found to be significantly upregulated in AML patients. Functional studies showed that knockdown of circAFF2 could significantly inhibit the proliferation of AML cells and promote their apoptosis. Overexpression of circAFF2 can have opposite effects. In vivo experiments showed that transplantation of AML cells with circAFF2 knockdown slowed the proliferation and infiltration and prolonged the survival time of mice compared to controls. Further studies showed that circAFF2 can promote the degradation of PML mRNA by binding to the 3'UTR of PML mRNA, thereby affecting the proliferation and apoptosis of AML cells. In conclusion, our work demonstrates that circAFF2 can bind to PML mRNA to regulate AML cell function, providing new insights into the mechanism of AML development and potential targets for clinical diagnosis and treatment.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391406","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

SNX5 facilitates the progression of gastric cancer by increasing the membrane localization of LRP5.

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-08 DOI: 10.1038/s41388-025-03298-z

Yi Le, Ling Zhou, Yan He, Juanjuan Zhou, Jinbo Zhan, Hongjiao Zhang, Xiao Chen, Jianping Xiong, Ziling Fang, Xiaojun Xiang

引用次数: 0

Editorial Expression of Concern: Caveolin-1 is regulated by c-myc and suppresses c-myc-induced apoptosis

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-07 DOI: 10.1038/s41388-025-03286-3

Terry L. Timme, Alexei Goltsov, Salahaldin Tahir, Likun Li, Jianxiang Wang, Chengzhen Ren, Randal N. Johnston, Timothy C. Thompson

引用次数: 0

PRSS23-eIF4E-c-Myc axis promotes gastric tumorigenesis and progression.

IF 6.9 1区医学

Oncogene Pub Date : 2025-02-07 DOI: 10.1038/s41388-025-03294-3

Xiaodong Zhou, Zixiang Guo, Yating Pan, Sicheng Yang, Runwei Yan

{"title":"PRSS23-eIF4E-c-Myc axis promotes gastric tumorigenesis and progression.","authors":"Xiaodong Zhou, Zixiang Guo, Yating Pan, Sicheng Yang, Runwei Yan","doi":"10.1038/s41388-025-03294-3","DOIUrl":"https://doi.org/10.1038/s41388-025-03294-3","url":null,"abstract":"Gastric cancer is one of the most common malignant tumors. Our previous study showed that PRSS23 expression is increased in human gastric cancer tissues and PRSS23 knockdown inhibits gastric cancer cell growth. This current study aims to uncover the mechanism underlying PRSS23's involvement in gastric tumorigenesis and progression. We established that PRSS23 influences gastric cancer growth both in vitro and in vivo by modulating the eIF4E-c-Myc axis (eIF4E, p-eIF4E, 4EBP1, p-4EBP1, and c-Myc). Our investigation revealed that PRSS23 interacts with eIF4E via its trypsin domain, while eIF4E binds to PRSS23 through the amino acid residue S209, as confirmed by co-IP and immunofluorescence assays. Multiplexed immunofluorescence assay demonstrated a significant elevation of PRSS23 and p-4EBP1 levels in 232 paired gastric cancer tissues. Moreover, in 49 patients exhibiting relatively high PRSS23 expression, the levels of eIF4E-c-Myc axis-related proteins were increased. Importantly, higher PRSS23 expression correlated significantly with increased lymph node metastasis and advanced clinical staging, leading to poorer patient prognosis. These results highlight the role of upregulated PRSS23 in promoting gastric tumorigenesis and progression by activating the eIF4E-c-Myc axis, underscoring the PRSS23-eIF4E-c-Myc axis as a promising therapeutic target for gastric cancer.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370965","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