Oncogene最新文献_第10页

Alternative splicing of bunched confers a dual role in hippo pathway-dependent growth and tumorigenesis. 簇的选择性剪接在河马通路依赖性生长和肿瘤发生中具有双重作用。

IF 6.9 1区医学

Oncogene Pub Date : 2025-04-02 DOI: 10.1038/s41388-025-03348-6

Pengjuan Guo, Sha Song, Yuxiao Niu, Xiaoyu Kuang, Dafa Zhou, Zizhang Zhou, Yanxiao Zhang, Xianjue Ma

{"title":"Alternative splicing of bunched confers a dual role in hippo pathway-dependent growth and tumorigenesis.","authors":"Pengjuan Guo, Sha Song, Yuxiao Niu, Xiaoyu Kuang, Dafa Zhou, Zizhang Zhou, Yanxiao Zhang, Xianjue Ma","doi":"10.1038/s41388-025-03348-6","DOIUrl":"10.1038/s41388-025-03348-6","url":null,"abstract":"Alternative splicing is a fundamental mechanism that generates functionally distinct proteins from individual genes, contributing to gene regulation and proteomic diversity. In Drosophila, the bunched (bun) gene, a member of the TSC-22 domain gene family, undergoes alternative splicing, yielding diverse protein isoforms involved in crucial biological processes. Nevertheless, the specific roles and regulatory mechanisms of each isoform remain elusive. Here, we employed CRISPR/Cas9 technology to introduce targeted deletions within the endogenous locus of the bun gene, resulting in the removal of either long or short isoforms. We discovered that the short isoforms demonstrated a growth-suppressive role, whereas the long isoforms exhibited a growth-promoting effect. Surprisingly, the long isoforms exhibited a remarkable dual functionality, as both deletion and amplification of long isoform expression impede the excess growth induced by Hippo pathway inactivation. Mechanistically, ectopically expressed Bun long isoforms act as the transcriptional suppressor by competitively binding to targets' promoter regions in conjunction with Yorkie/Scalloped (Yki/Sd), thereby inhibiting its transcriptional outputs and ultimately leading to the growth suppression. These findings unveil the intricate interaction between distinct spliced isoforms of Bun and oncogenic outcomes, highlighting Bun long isoforms as the critical transcription suppressor regulating Hippo pathway inactivation-mediated growth and tumorigenesis in Drosophila.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772762","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

Editorial Expression of Concern: Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer 编辑关注的表达：乳腺癌中致癌microRNA-17-92/ZBTB4/特异性蛋白轴的鉴定。

IF 6.9 1区医学

Oncogene Pub Date : 2025-04-01 DOI: 10.1038/s41388-025-03363-7

K. Kim, G. Chadalapaka, S. -O Lee, D. Yamada, X. Sastre-Garau, P. -A Defossez, Y. -Y Park, J. -S Lee, S. Safe

引用次数: 0

Correction: Combination strategies with PARP inhibitors in BRCA-mutated triple-negative breast cancer: overcoming resistance mechanisms 纠正：在brca突变的三阴性乳腺癌中联合PARP抑制剂的策略：克服耐药机制。

IF 6.9 1区医学

Oncogene Pub Date : 2025-04-01 DOI: 10.1038/s41388-025-03364-6

Aditi Jain, Alan Barge, Christopher N. Parris

引用次数: 0

Active R-RAS2/TC21 prevents cell cycle arrest and morphological alterations in mouse embryonic fibroblasts lacking RAS proteins. 活性R-RAS2/TC21可阻止缺乏RAS蛋白的小鼠胚胎成纤维细胞的细胞周期阻滞和形态改变。

IF 6.9 1区医学

Oncogene Pub Date : 2025-03-31 DOI: 10.1038/s41388-025-03367-3

Isabel Fernández-Pisonero, L Francisco Lorenzo-Martín, Mattias Drosten, Eugenio Santos, Mariano Barbacid, Balbino Alarcón, Xosé R Bustelo

{"title":"Active R-RAS2/TC21 prevents cell cycle arrest and morphological alterations in mouse embryonic fibroblasts lacking RAS proteins.","authors":"Isabel Fernández-Pisonero, L Francisco Lorenzo-Martín, Mattias Drosten, Eugenio Santos, Mariano Barbacid, Balbino Alarcón, Xosé R Bustelo","doi":"10.1038/s41388-025-03367-3","DOIUrl":"https://doi.org/10.1038/s41388-025-03367-3","url":null,"abstract":"R-RAS2/TC21, a member of the R-RAS subfamily of GTP-binding proteins, shares structural and signaling properties with the RAS subfamily proteins H-, K-, and N-RAS. However, little information is available regarding its role in normal cells and the level of functional redundancy with R-RAS and classical RAS proteins. In this work, we used loss and gain-of-function approaches to assess these issues in mouse embryonic fibroblasts (MEFs). Using primary MEFs from Rras2-/-, Rras-/- or Rras-/-; Rras2-/- embryos, we show here that endogenous R-RAS2/TC21 is required for activation of the phosphatidylinositol 3 kinase (PI3K)-AKT axis, the proliferation, and the adhesion properties of these cells. Endogenous R-RAS does not influence any of these cell parameters. We also show that the depletion of R-RAS2/TC21 worsens the proliferative and morphological defects elicited by the combined loss of H-, K- and N-RAS proteins in MEFs. Conversely, the ectopic expression of an active version of R-RAS2/TC21, but not of R-RAS, overcomes such defects. This rescue activity involves the inhibition of the tumor suppressor TP53 and is PI3K-, mTORC-, and MEK/ERK-dependent. These results indicate that R-RAS2/TC21, R-RAS, and RAS subfamily GTPases play different roles in MEFs. They also show that R-RAS2 provides subsidiary signals that are essential for the short-term proliferation and long-term viability of MEFs lacking RAS signaling.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753857","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

USP5 deubiquitinates and stabilizes IMPDH2, to promote hepatocellular carcinoma progression. USP5去泛素化并稳定IMPDH2，促进肝细胞癌进展。

IF 6.9 1区医学

Oncogene Pub Date : 2025-03-31 DOI: 10.1038/s41388-025-03355-7

Shuoyi Jiang, Liyang Jiang, Yingying Xu, Yunju Ma, Yiran Deng, Can Jiao, Min Yin, Chao Qin, Jiale Li, Li Zhang, She Chen

{"title":"USP5 deubiquitinates and stabilizes IMPDH2, to promote hepatocellular carcinoma progression.","authors":"Shuoyi Jiang, Liyang Jiang, Yingying Xu, Yunju Ma, Yiran Deng, Can Jiao, Min Yin, Chao Qin, Jiale Li, Li Zhang, She Chen","doi":"10.1038/s41388-025-03355-7","DOIUrl":"10.1038/s41388-025-03355-7","url":null,"abstract":"Modulating deubiquitinase activity is an emerging therapeutic approach for cancer. In this study, ubiquitin-specific protease 5 (USP5), a deubiquitinase, was found to be frequently overexpressed in hepatocellular carcinoma (HCC) and associated with poor prognosis in patients with HCC. Inosine monophosphate dehydrogenase 2 (IMPDH2) was identified as a binding partner of USP5. USP5 N-terminal domain (cryptic ZnF-UBP and ZnF-UBP domain) interacted with IMPDH2 (251-514 aa). IMPDH2 positively correlated with USP5 expression in HCC. Mechanistically, USP5 removed Lys48-linked ubiquitin chains from IMPDH2 through its deubiquitinase activity, preventing its ubiquitin-mediated degradation and stabilizing IMPDH2. The USP5-IMPDH2 axis promoted HCC proliferation, and metastasis mediated by epithelial-mesenchymal transition (EMT) process in HCC cells and Huh7 xenograft tumors in zebrafish. Notably, GTP biosynthesis pathway was involved in HCC progression induced by USP5. Furthermore, administration of WP1130, a USP5 inhibitor, or IMPDH2 reduction by shRNA facilitated the tumor-suppressive role of sorafenib in HCC cells and Huh7 xenograft tumors in nude mice. Together, we identified IMPDH2 as a substrate of USP5, which participates in USP5 induced promotion of HCC progression. Targeting the USP5-IMPDH2 axis might offer potential therapeutic benefits for patients with HCC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753869","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

Reciprocal regulation between ferroptosis and STING-type I interferon pathway suppresses head and neck squamous cell carcinoma growth through dendritic cell maturation. 铁下垂与sting - I型干扰素通路相互调控，通过树突状细胞成熟抑制头颈部鳞状细胞癌的生长。

IF 6.9 1区医学

Oncogene Pub Date : 2025-03-31 DOI: 10.1038/s41388-025-03368-2

Mingyu Li, Shufang Jin, Hailong Ma, Xi Yang, Zhiyuan Zhang

{"title":"Reciprocal regulation between ferroptosis and STING-type I interferon pathway suppresses head and neck squamous cell carcinoma growth through dendritic cell maturation.","authors":"Mingyu Li, Shufang Jin, Hailong Ma, Xi Yang, Zhiyuan Zhang","doi":"10.1038/s41388-025-03368-2","DOIUrl":"10.1038/s41388-025-03368-2","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) presents a serious clinical challenge mainly due to its resistance to conventional therapies and its complex, immunosuppressive tumor microenvironment. While recent studies have identified ferroptosis as a new therapeutic option, its impact on the immune microenvironment in HNSCC remains controversial, which may hinder its translational application. Although the role of the stimulator of interferon genes (STING)-type I interferon (IFN-I) pathway in antitumor immune responses has been widely investigated, its relationship with ferroptosis in HNSCC has not been fully explored. In this study, we discovered that ferroptosis in HNSCC inhibited tumor growth, activated STING-IFN-I pathway and subsequently improved recruitment and maturation of dendritic cells. We further demonstrated that IFN-I could enhance ferroptosis by inhibiting xCT-glutathione peroxidase 4 (GPX4) antioxidant system. To harness this positive feedback loop, we treated HNSCC tumors with both ferroptosis inducer and STING agonist, resulting in significant tumor suppression, elevated ferroptosis levels and enhanced dendritic cell infiltration. Overall, our findings reveal a mutually regulatory relationship between ferroptosis and the intrinsic STING-IFN-I pathway, providing novel insights into immune-mediated tumor suppression and suggesting its potential as therapeutic approach in HNSCC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753861","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

sEV-mediated intercellular transformation from MGAT4A^High to MGAT4A^Low tumor cells via the HOTAIRM1/miR-196b-5p axis promotes apoptosis resistance in CTCL. sev介导的肿瘤细胞通过HOTAIRM1/miR-196b-5p轴从MGAT4AHigh向mgat4allow的细胞间转化促进了CTCL的凋亡抵抗。

IF 6.9 1区医学

Oncogene Pub Date : 2025-03-28 DOI: 10.1038/s41388-025-03356-6

Jiachen Sun, Tingting Li, Jing Cui, Lihua Zhang, Guanyu Wang, Chuan Ma, Chunlei Zhang, Yimeng Wang

{"title":"sEV-mediated intercellular transformation from MGAT4AHigh to MGAT4ALow tumor cells via the HOTAIRM1/miR-196b-5p axis promotes apoptosis resistance in CTCL.","authors":"Jiachen Sun, Tingting Li, Jing Cui, Lihua Zhang, Guanyu Wang, Chuan Ma, Chunlei Zhang, Yimeng Wang","doi":"10.1038/s41388-025-03356-6","DOIUrl":"10.1038/s41388-025-03356-6","url":null,"abstract":"ncRNAs encapsulated in small extracellular vesicles (sEVs) facilitate intercellular communication and are associated with tumor progression. lncRNA-HOTAIRM1 is aberrantly expressed in various cancers. However, HOTAIRM1 expression and its downstream ceRNA network in CTCL remains unclear. In this study, we found that HOTAIRM1 was reduced in CTCL. Elevated HOTAIRM1 inhibited proliferation and induced apoptosis in vitro, resulting in reduced in vivo tumorigenic capacity. Whole-transcriptome sequencing and scRNA-Seq confirmed that differential expression of HOTAIRM1/miR-196b-5p/MGAT4A axis induces apoptosis resistance in CTCL. Mechanistically, reduced MGAT4A expression in CTCL leads to decreased N-glycosylation modification of membrane proteins and reduced Galectin-1 affinity, thereby inducing partial resistance to Galectin-1-induced apoptosis. Meanwhile, benign CD4 + T cells show sensitivity to Galectin-1-induced apoptosis due to their relatively higher MGAT4A expression. Furthermore, MGAT4ALow CTCL tumor cells transformed MGAT4AHigh CD4+ benign cells into MGAT4ALow cells by secreting sEVs containing miR-196b-5p, thereby reducing Galectin-1 binding and inducing apoptosis resistance. Engineered sEVs from HOTAIRM1-overexpressing cells contain elevated HOTAIRM1, which can specifically target malignant T cells, with reduced miR-196b-5p and increased MGAT4A, demonstrating apoptosis-inducing and tumor-suppressive effects in CTCL. This study identified changes in HOTAIRM1/miR-196b-5p/MGAT4A axis and N-glycosylation modifications in CTCL. Engineered HOTAIRM1-loaded sEVs demonstrated promising targeting and therapeutic effects in CTCL.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743005","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

Deciphering permissivity of human tumor ecosystems to oncolytic viruses 破译人类肿瘤生态系统对溶瘤病毒的容忍度。

IF 6.9 1区医学

Oncogene Pub Date : 2025-03-27 DOI: 10.1038/s41388-025-03357-5

Benjamin Schoeps, Ulrich M. Lauer, Knut Elbers

引用次数: 0

SUMOylation facilitates the stability of BCR-ABL to promote chronic myeloid leukemia progression. SUMOylation促进BCR-ABL的稳定性，促进慢性髓性白血病的进展。

IF 6.9 1区医学

Oncogene Pub Date : 2025-03-27 DOI: 10.1038/s41388-025-03350-y

Lu Zhang, Xuefeng Wang, Dongmei Hu, Shijie Li, Mingshan Sun, Qian Liu, Huimin Feng, Minran Zhou, Chunyan Chen, Huan Zhou, Sai Ma

引用次数: 0

Characterizing the tumor suppressor activity of FLCN in Birt-Hogg-Dubé syndrome cell models through transcriptomic and proteomic analysis. 通过转录组学和蛋白质组学分析表征FLCN在birt - hogg - dub<s:1>综合征细胞模型中的抑瘤活性。

IF 6.9 1区医学

Oncogene Pub Date : 2025-03-25 DOI: 10.1038/s41388-025-03325-z

Rachel-Ann Jones, Elaine A Dunlop, Jesse D Champion, Peter F Doubleday, Tijs Claessens, Zahra Jalali, Sara Seifan, Iain A Perry, Peter Giles, Oliver Harrison, Barry J Coull, Arjan C Houweling, Arnim Pause, Bryan A Ballif, Andrew R Tee

{"title":"Characterizing the tumor suppressor activity of FLCN in Birt-Hogg-Dubé syndrome cell models through transcriptomic and proteomic analysis.","authors":"Rachel-Ann Jones, Elaine A Dunlop, Jesse D Champion, Peter F Doubleday, Tijs Claessens, Zahra Jalali, Sara Seifan, Iain A Perry, Peter Giles, Oliver Harrison, Barry J Coull, Arjan C Houweling, Arnim Pause, Bryan A Ballif, Andrew R Tee","doi":"10.1038/s41388-025-03325-z","DOIUrl":"10.1038/s41388-025-03325-z","url":null,"abstract":"Birt-Hogg-Dubé syndrome (BHD) patients are uniquely susceptible to all renal tumor subtypes. However, the underlying mechanism of carcinogenesis is unclear. To study cancer development in BHD, we used human proximal kidney (HK2) cells and found that long-term folliculin (FLCN) knockdown was required to increase the tumorigenic potential of these cells, as evidenced by the formation of larger spheroids under nonadherent conditions. Transcriptomic and proteomic analyses revealed links between the FLCN, cell cycle control and DNA damage response (DDR) machinery. In addition, HK2 cells lacking FLCN had an altered transcriptome profile and enriched cell cycle control genes. G1/S cell cycle checkpoint signaling was compromised by increased protein levels of cyclin D1 (CCND1) and hyperphosphorylation of retinoblastoma 1 (RB1). A FLCN interactome screen revealed that FLCN binds to DNA-dependent protein kinase (DNA-PK). This novel interaction was reversed in an irradiation-responsive manner. Knockdown of FLCN in HK2 cells caused a marked increase in γH2AX and RB1 phosphorylation. The levels of both CCND1 and phosphorylated RB1 remained high during DNA damage, which was associated with defective cell cycle control caused by FLCN knockdown. Furthermore, Flcn-knockdown C. elegans were defective in cell cycle arrest caused by DNA damage. This work revealed that long-term FLCN loss and associated cell cycle defects in BHD patients could contribute to their increased risk of cancer.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710833","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