Cancer gene therapy最新文献_第10页

Pathophysiological role of ion channels and transporters in hepatocellular carcinoma 离子通道和转运体在肝细胞癌中的病理生理学作用。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-07-24 DOI: 10.1038/s41417-024-00782-8

Li Zhang, Hong Gu, Xin Li, Yongfeng Wang, Shun Yao, Xingyue Chen, Liming Zheng, Xingyue Yang, Qian Du, Jiaxing An, Guorong Wen, Jiaxing Zhu, Hai Jin, Biguang Tuo

{"title":"Pathophysiological role of ion channels and transporters in hepatocellular carcinoma","authors":"Li Zhang, Hong Gu, Xin Li, Yongfeng Wang, Shun Yao, Xingyue Chen, Liming Zheng, Xingyue Yang, Qian Du, Jiaxing An, Guorong Wen, Jiaxing Zhu, Hai Jin, Biguang Tuo","doi":"10.1038/s41417-024-00782-8","DOIUrl":"10.1038/s41417-024-00782-8","url":null,"abstract":"The incidence of hepatocellular carcinoma (HCC) has continued to increase annually worldwide, and HCC has become a common cause of cancer-related death. Despite great progress in understanding the molecular mechanisms underlying HCC development, the treatment of HCC remains a considerable challenge. Thus, the survival and prognosis of HCC patients remain extremely poor. In recent years, the role of ion channels in the pathogenesis of diseases has become a hot topic. In normal liver tissue, ion channels and transporters maintain water and electrolyte balance and acid‒base homeostasis. However, dysfunction of these ion channels and transporters can lead to the development and progression of HCC, and thus these ion channels and transporters are expected to become new therapeutic targets. In this review, ion channels and transporters associated with HCC are reviewed, and potential targets for new and effective therapies are proposed.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 11","pages":"1611-1618"},"PeriodicalIF":4.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00782-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Atypical phosphatase DUSP11 inhibition promotes nc886 expression and potentiates gemcitabine-mediated cell death through NF-kB modulation 抑制非典型磷酸酶DUSP11可促进nc886的表达，并通过NF-kB调节增强吉西他滨介导的细胞死亡。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-07-24 DOI: 10.1038/s41417-024-00804-5

Verena Silva Santos, Gabriela Maciel Vieira, Mariana Tannús Ruckert, Pamela Viani de Andrade, Luis Fernando Nagano, Mariângela Ottoboni Brunaldi, José Sebastião Dos Santos, Vanessa Silva Silveira

{"title":"Atypical phosphatase DUSP11 inhibition promotes nc886 expression and potentiates gemcitabine-mediated cell death through NF-kB modulation","authors":"Verena Silva Santos, Gabriela Maciel Vieira, Mariana Tannús Ruckert, Pamela Viani de Andrade, Luis Fernando Nagano, Mariângela Ottoboni Brunaldi, José Sebastião Dos Santos, Vanessa Silva Silveira","doi":"10.1038/s41417-024-00804-5","DOIUrl":"10.1038/s41417-024-00804-5","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers among all solid tumors. First-line treatment relies on gemcitabine (Gem) and despite treatment improvements, refractoriness remains a universal challenge. Attempts to decipher how feedback-loops control signaling pathways towards drug resistance have gained attention in recent years, particularly focused on the role of phosphatases. In this study, a CRISPR/Cas9-based phenotypic screen was performed to identify members from the dual-specificity phosphatases (DUSP) family potentially acting on Gem response in PDAC cells. The approach revealed the atypical RNA phosphatase DUSP11 as a potential target, whose inhibition creates vulnerability of PDAC cells to Gem. DUSP11 genetic inhibition impaired cell survival and promoted apoptosis, synergistically enhancing Gem cytotoxicity. In silico transcriptome analysis of RNA-seq data from PDAC human samples identified NF-ĸB signaling pathway highly correlated with DUSP11 upregulation. Consistently, Gem-induced NF-ĸB phosphorylation was blocked upon DUSP11 inhibition in vitro. Mechanistically, we found that DUSP11 directly impacts nc886 expression and modulates PKR-NF-ĸB signaling cascade after Gem exposure in PDAC cells resulting in resistance to Gem-induced cell death. In conclusion, this study provides new insights on DUSP11 role in RNA biology and Gem response in PDAC cells.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 9","pages":"1402-1411"},"PeriodicalIF":4.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Therapeutic activity of retroviral replicating vector-mediated gene therapy in combination with anti-PD-1 antibody in a murine pancreatic cancer model 逆转录病毒复制载体介导的基因疗法与抗-PD-1 抗体相结合在小鼠胰腺癌模型中的治疗活性。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-07-23 DOI: 10.1038/s41417-024-00810-7

Hiroki Niwa, Toru Nakamura, Hiroki Kushiya, Tomotaka Kuraya, Kazuho Inoko, Akihito Inagaki, Tomohiro Suzuki, Katsunori Sasaki, Takahiro Tsuchikawa, Kei Hiraoka, Toshiaki Shichinohe, Yutaka Hatanaka, Douglas J. Jolly, Noriyuki Kasahara, Satoshi Hirano

{"title":"Therapeutic activity of retroviral replicating vector-mediated gene therapy in combination with anti-PD-1 antibody in a murine pancreatic cancer model","authors":"Hiroki Niwa, Toru Nakamura, Hiroki Kushiya, Tomotaka Kuraya, Kazuho Inoko, Akihito Inagaki, Tomohiro Suzuki, Katsunori Sasaki, Takahiro Tsuchikawa, Kei Hiraoka, Toshiaki Shichinohe, Yutaka Hatanaka, Douglas J. Jolly, Noriyuki Kasahara, Satoshi Hirano","doi":"10.1038/s41417-024-00810-7","DOIUrl":"10.1038/s41417-024-00810-7","url":null,"abstract":"Toca 511, a tumor-selective retroviral replicating vector encoding the yeast cytosine deaminase (yCD) gene, exerts direct antitumor effects through intratumoral prodrug 5-fluorocytosine (5-FC) conversion to active drug 5-fluorouracil by yCD, and has demonstrated therapeutic efficacy in preclinical and clinical trials of various cancers. Toca 511/5-FC treatment may also induce antitumor immunity. Here, we first examined antitumor immune responses activated by Toca 511/5-FC treatment in an immunocompetent murine pancreatic cancer model. We then evaluated the therapeutic effects achieved in combination with anti-programmed cell death protein 1 antibody. In the bilateral subcutaneous tumor model, as compared with the control group, enhanced CD8+ T-cell-mediated cytotoxicity and increased T-cell infiltration in Toca 511-untransduced contralateral tumors were observed. Furthermore, the expression levels of T-cell co-inhibitory receptors on CD8+ T-cells increased during treatment. In the bilateral subcutaneous tumor model, combination therapy showed significantly stronger tumor growth inhibition than that achieved with either monotherapy. In an orthotopic tumor and peritoneal dissemination model, the combination therapy resulted in complete regression in both transduced orthotopic tumors and untransduced peritoneal dissemination. Thus, Toca 511/5-FC treatment induced a systemic antitumor immune response, and the combination therapy could be a promising clinical strategy for treating metastatic pancreatic cancer.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 9","pages":"1390-1401"},"PeriodicalIF":4.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Atypical cellular responses mediated by intracellular constitutive active TrkB (NTRK2) kinase domains and a solely intracellular NTRK2-fusion oncogene 由细胞内组成型活性TrkB（NTRK2）激酶结构域和单纯细胞内NTRK2融合型癌基因介导的非典型细胞反应

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-07-22 DOI: 10.1038/s41417-024-00809-0

Rohini Gupta, Melanie Dittmeier, Gisela Wohlleben, Vera Nickl, Thorsten Bischler, Vanessa Luzak, Vanessa Wegat, Dennis Doll, Annemarie Sodmann, Elena Bady, Georg Langlhofer, Britta Wachter, Steven Havlicek, Jahnve Gupta, Evi Horn, Patrick Lüningschrör, Carmen Villmann, Bülent Polat, Jörg Wischhusen, Camelia M. Monoranu, Jochen Kuper, Robert Blum

{"title":"Atypical cellular responses mediated by intracellular constitutive active TrkB (NTRK2) kinase domains and a solely intracellular NTRK2-fusion oncogene","authors":"Rohini Gupta, Melanie Dittmeier, Gisela Wohlleben, Vera Nickl, Thorsten Bischler, Vanessa Luzak, Vanessa Wegat, Dennis Doll, Annemarie Sodmann, Elena Bady, Georg Langlhofer, Britta Wachter, Steven Havlicek, Jahnve Gupta, Evi Horn, Patrick Lüningschrör, Carmen Villmann, Bülent Polat, Jörg Wischhusen, Camelia M. Monoranu, Jochen Kuper, Robert Blum","doi":"10.1038/s41417-024-00809-0","DOIUrl":"10.1038/s41417-024-00809-0","url":null,"abstract":"Trk (NTRK) receptor and NTRK gene fusions are oncogenic drivers of a wide variety of tumors. Although Trk receptors are typically activated at the cell surface, signaling of constitutive active Trk and diverse intracellular NTRK fusion oncogenes is barely investigated. Here, we show that a high intracellular abundance is sufficient for neurotrophin-independent, constitutive activation of TrkB kinase domains. In HEK293 cells, constitutive active TrkB kinase and an intracellular NTRK2-fusion oncogene (SQSTM1-NTRK2) reduced actin filopodia dynamics, phosphorylated FAK, and altered the cell morphology. Atypical cellular responses could be mimicked with the intracellular kinase domain, which did not activate the Trk-associated MAPK/ERK pathway. In glioblastoma-like U87MG cells, expression of TrkB or SQSTM1-NTRK2 reduced cell motility and caused drastic changes in the transcriptome. Clinically approved Trk inhibitors or mutating Y705 in the kinase domain, blocked the cellular effects and transcriptome changes. Atypical signaling was also seen for TrkA and TrkC. Moreover, hallmarks of atypical pTrk kinase were found in biopsies of Nestin-positive glioblastoma. Therefore, we suggest Western blot-like immunoassay screening of NTRK-related (brain) tumor biopsies to identify patients with atypical panTrk or phosphoTrk signals. Such patients could be candidates for treatment with NTRK inhibitors such as Larotrectinhib or Entrectinhib.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 9","pages":"1357-1379"},"PeriodicalIF":4.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00809-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

HADHA promotes glioma progression by accelerating MDM2-mediated p53 ubiquitination HADHA 通过加速 MDM2- 介导的 p53 泛素化促进胶质瘤进展

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-07-22 DOI: 10.1038/s41417-024-00801-8

Rudong Chen, Hao Chen, Changchen Hu

{"title":"HADHA promotes glioma progression by accelerating MDM2-mediated p53 ubiquitination","authors":"Rudong Chen, Hao Chen, Changchen Hu","doi":"10.1038/s41417-024-00801-8","DOIUrl":"10.1038/s41417-024-00801-8","url":null,"abstract":"Glioma represents a notoriously aggressive and malignant tumor that targets the central nervous system, with a poor prognosis for patients. In this research, we set out to examine the role of hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA) in glioma, its clinical significance, as well as its potential biological mechanisms. In this study, we used immunohistochemistry staining to assess the expression level of HADHA in glioma tissues. We also evaluated the correlation between HADHA expression and patient survival using the Kaplan–Meier method. To determine the role of HADHA in glioma cells, we conducted loss-of-function assays in vitro and in vivo. Additionally, we utilized co-immunoprecipitation and protein stability assays to investigate the potential mechanisms involving HADHA, MDM2, and p53 in glioma. Our research findings indicate that gliomas exhibit high levels of HADHA. Clinically, high expression of HADHA suggests an increased risk of malignant tumors, recurrence, and reduced survival rates. Functionally, knocking down HADHA can lead to decreased proliferation, enhanced apoptosis, and inhibited migration of glioma cells. Mechanistically, HADHA accelerates MDM2-mediated p53 ubiquitination through interaction with MDM2. Consistently, MDM2 knockdown or overexpression of p53 can attenuate the promoting effect of HADHA overexpression on the malignant progression of glioma. We have discovered a novel role of HADHA in promoting MDM2-mediated p53 ubiquitination, which contributes to the progression of glioma. This finding provides a new perspective to understand the pathogenesis of glioma and offers a potential target for developing innovative therapeutic strategies.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 9","pages":"1380-1389"},"PeriodicalIF":4.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

NF-κB role on tumor proliferation, migration, invasion and immune escape NF-κB 在肿瘤增殖、迁移、侵袭和免疫逃逸中的作用。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-07-20 DOI: 10.1038/s41417-024-00811-6

Afrasyab Khan, Yao Zhang, Ningna Ma, Juanjuan Shi, Yongzhong Hou

引用次数: 0

CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status CCT6A 通过靶向与 p53 状态相关的 BIRC5 促进结肠癌细胞增殖。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-07-13 DOI: 10.1038/s41417-024-00806-3

Han Zhang, Taotao Zheng, Chuan Qin, Xinyue Zhang, Han Lin, Xiaoping Huang, Qiang Liu, Shichuan Chang, Li Zhang, Jing Guo, Yao Zhang, Chunxiang Bian, Huawen Liu

{"title":"CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status","authors":"Han Zhang, Taotao Zheng, Chuan Qin, Xinyue Zhang, Han Lin, Xiaoping Huang, Qiang Liu, Shichuan Chang, Li Zhang, Jing Guo, Yao Zhang, Chunxiang Bian, Huawen Liu","doi":"10.1038/s41417-024-00806-3","DOIUrl":"10.1038/s41417-024-00806-3","url":null,"abstract":"Chaperonin-containing TCP1 (CCT) is a multi-subunit complex, known to participate the correct folding of many proteins. Currently, the mechanism underlying CCT subunits in cancer progression is incompletely understood. Based on data analysis, the expression of CCT subunit 6 A (CCT6A) is found higher than the other subunits of CCT and correlated with an unfavorable prognosis in colon cancer. Here, we find CCT6A silencing suppresses colon cancer proliferation and survival phenotype in vitro and in vivo. CCT6A plays a role in cellular process, including the cell cycle, p53, and apoptosis signaling pathways. Further investigations have shown direct binding between CCT6A and both Wtp53 and Mutp53, and BIRC5 is found to act downstream of CCT6A. The highlight is that CCT6A inhibition significantly reduces BIRC5 expression independent of Wtp53 levels in Wtp53 cells. Conversely, in Mutp53 cells, downregulation of BIRC5 by CCT6A inhibition mainly depends on Mutp53 levels. Additionally, combined CCT6A inhibition and Wtp53 overexpression in Mutp53 cell lines effectively suppresses cell proliferation. It is concluded CCT6A is a potential oncogene that influences BIRC5 through distinct pathways in Wtp53 and Mutp53 cells.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1151-1163"},"PeriodicalIF":4.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Long-term severe hypoxia adaptation induces non-canonical EMT and a novel Wilms Tumor 1 (WT1) isoform 长期严重缺氧适应会诱导非典型EMT和一种新型Wilms Tumor 1（WT1）同工酶。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-07-08 DOI: 10.1038/s41417-024-00795-3

Jordan Quenneville, Albert Feghaly, Margaux Tual, Kiersten Thomas, François Major, Etienne Gagnon

{"title":"Long-term severe hypoxia adaptation induces non-canonical EMT and a novel Wilms Tumor 1 (WT1) isoform","authors":"Jordan Quenneville, Albert Feghaly, Margaux Tual, Kiersten Thomas, François Major, Etienne Gagnon","doi":"10.1038/s41417-024-00795-3","DOIUrl":"10.1038/s41417-024-00795-3","url":null,"abstract":"The majority of cancer deaths are caused by solid tumors, where the four most prevalent cancers (breast, lung, colorectal and prostate) account for more than 60% of all cases (1). Tumor cell heterogeneity driven by variable cancer microenvironments, such as hypoxia, is a key determinant of therapeutic outcome. We developed a novel culture protocol, termed the Long-Term Hypoxia (LTHY) time course, to recapitulate the gradual development of severe hypoxia seen in vivo to mimic conditions observed in primary tumors. Cells subjected to LTHY underwent a non-canonical epithelial to mesenchymal transition (EMT) based on miRNA and mRNA signatures as well as displayed EMT-like morphological changes. Concomitant to this, we report production of a novel truncated isoform of WT1 transcription factor (tWt1), a non-canonical EMT driver, with expression driven by a yet undescribed intronic promoter through hypoxia-responsive elements (HREs). We further demonstrated that tWt1 initiates translation from an intron-derived start codon, retains proper subcellular localization and DNA binding. A similar tWt1 is also expressed in LTHY-cultured human cancer cell lines as well as primary cancers and predicts long-term patient survival. Our study not only demonstrates the importance of culture conditions that better mimic those observed in primary cancers, especially with regards to hypoxia, but also identifies a novel isoform of WT1 which correlates with poor long-term survival in ovarian cancer.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1237-1250"},"PeriodicalIF":4.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00795-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: H3.3-G34W in giant cell tumor of bone functionally aligns with the exon choice repressor hnRNPA1L2 更正：骨巨细胞瘤中的 H3.3-G34W 与外显子选择抑制因子 hnRNPA1L2 在功能上一致。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-27 DOI: 10.1038/s41417-024-00803-6

Eunbi Lee, Yoon Jung Park, Anders M. Lindroth

引用次数: 0

Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model 在原位胶质母细胞瘤小鼠模型中通过靶向 COUP-TFII 抗血管生成和抗免疫抑制基因疗法。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-26 DOI: 10.1038/s41417-024-00799-z

Fei Wang, Shuo Zhang, Fengjiao Sun, Weiwei Chen, Cuilan Liu, Hongliang Dong, Bingjie Cui, Lingyu Li, Chunlong Sun, Wen Du, Bin Liu, Wanfeng Fan, Jiong Deng, Clemens A. Schmitt, Xiuwen Wang, Jing Du

{"title":"Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model","authors":"Fei Wang, Shuo Zhang, Fengjiao Sun, Weiwei Chen, Cuilan Liu, Hongliang Dong, Bingjie Cui, Lingyu Li, Chunlong Sun, Wen Du, Bin Liu, Wanfeng Fan, Jiong Deng, Clemens A. Schmitt, Xiuwen Wang, Jing Du","doi":"10.1038/s41417-024-00799-z","DOIUrl":"10.1038/s41417-024-00799-z","url":null,"abstract":"Glioblastoma (GBM) is the most common and aggressive primary brain cancer; angiogenesis and immunosuppression exacerbate GBM progression. COUP-TFII demonstrates pro-angiogenesis activity; however, its role in glioma progression remains unclear. This study revealed that COUP-TFII promotes angiogenesis in gliomas by inducing transdifferentiation of glioma cells into endothelial-like cells. Mechanistic investigation suggested that COUP-TFII as a transcription factor exerts its function via binding to the promoter of TXNIP. Interestingly, COUP-TFII knockdown attenuated tumorigenesis and tumor progression in an immunocompetent mouse model but promoted tumor progression in an immuno-deficient mouse model. As an explanation, repression of COUP-TFII induces cellular senescence and activates immune surveillance in glioma cells in vitro and in vivo. In addition, we used heparin–polyethyleneimine (HPEI) nanoparticles to deliver COUP-TFII shRNA, which regulated tumor angiogenesis and immunosuppression in an in situ GBM mouse model. This study provides a novel strategy and potential therapeutic targets to treat GBM.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1135-1150"},"PeriodicalIF":4.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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