Cancer gene therapy最新文献_第9页

H3.3-G34W in giant cell tumor of bone functionally aligns with the exon choice repressor hnRNPA1L2 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 : 2024-05-29 DOI: 10.1038/s41417-024-00776-6

Eunbi Lee, Yoon Jung Park, Anders M. Lindroth

{"title":"H3.3-G34W in giant cell tumor of bone functionally aligns with the exon choice repressor hnRNPA1L2","authors":"Eunbi Lee, Yoon Jung Park, Anders M. Lindroth","doi":"10.1038/s41417-024-00776-6","DOIUrl":"10.1038/s41417-024-00776-6","url":null,"abstract":"RNA processing is an essential post-transcriptional phenomenon that provides the necessary complexity of transcript diversity prior to translation. Aberrations in this process could contribute to tumourigenesis, and we have previously reported increased splicing alterations in giant cell tumor of bone (GCTB), which carries mutations in the histone variant H3.3 encoding glycine 34 substituted for tryptophan (H3.3-G34W). G34W interacts with several splicing factors, most notably the trans-acting splicing factor hnRNPA1L2. To gain a deeper understanding of RNA processing in GCTB and isogenic HeLa cells with H3.3-G34W, we generated RNA-immunoprecipitation sequencing data from hnRNPA1L2 and H3.3-G34W associated RNAs, which showed that 80% overlapped across genic regions and were frequently annotated as E2F transcription factor binding sites. Splicing aberrations in both GCTB and HeLa cells with H3.3-G34W were significantly enriched for known hnRNPA1L2 binding motifs (p value < 0.01). This splicing aberration differed from hnRNPA1L2 knockouts, which showed alterations independent of H3.3-G34W. Of functional significance, hnRNPA1L2 was redistributed to closely match the H3.3 pattern, likely driven by G34W, and to loci not occupied in normal parental cells. Taken together, our data reveal a functional overlap between hnRNPA1L2 and H3.3-G34W with likely significant consequences for RNA processing during GCTB pathogenesis. This provides novel opportunities for therapeutic intervention in future modus operandi.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1177-1185"},"PeriodicalIF":4.8,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00776-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141169366","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

Unveiling mitochondrial and ribosomal gene deregulation and tumor microenvironment dynamics in acute myeloid leukemia 揭示急性髓性白血病的线粒体和核糖体基因失调及肿瘤微环境动态。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-28 DOI: 10.1038/s41417-024-00788-2

Chao Ma, Yuchao Hao, Bo Shi, Zheng Wu, Di Jin, Xiao Yu, Bilian Jin

{"title":"Unveiling mitochondrial and ribosomal gene deregulation and tumor microenvironment dynamics in acute myeloid leukemia","authors":"Chao Ma, Yuchao Hao, Bo Shi, Zheng Wu, Di Jin, Xiao Yu, Bilian Jin","doi":"10.1038/s41417-024-00788-2","DOIUrl":"10.1038/s41417-024-00788-2","url":null,"abstract":"Acute myeloid leukemia (AML) is a malignant clonal hematopoietic disease with a poor prognosis. Understanding the interaction between leukemic cells and the tumor microenvironment (TME) can help predict the prognosis of leukemia and guide its treatment. Re-analyzing the scRNA-seq data from the CSC and G20 cohorts, using a Python-based pipeline including machine-learning-based scVI-tools, recapitulated the distinct hierarchical structure within the samples of AML patients. Weighted correlation network analysis (WGCNA) was conducted to construct a weighted gene co-expression network and to identify gene modules primarily focusing on hematopoietic stem cells (HSCs), multipotent progenitors (MPPs), and natural killer (NK) cells. The analysis revealed significant deregulation in gene modules associated with aerobic respiration and ribosomal/cytoplasmic translation. Cell–cell communications were elucidated by the CellChat package, revealing an imbalance of activating and inhibitory immune signaling pathways. Interception of genes upregulated in leukemic HSCs & MPPs as well as in NKG2A-high NK cells was used to construct prognostic models. Normal Cox and artificial neural network models based on 10 genes were developed. The study reveals the deregulation of mitochondrial and ribosomal genes in AML patients and suggests the co-occurrence of stimulatory and inhibitory factors in the AML TME.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"1034-1048"},"PeriodicalIF":4.8,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161045","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

CircPKN2 promotes ferroptosis in bladder cancer by promoting the ubiquitination of Stearoyl-CoA Desaturase 1 CircPKN2通过促进硬脂酰-CoA去饱和酶1的泛素化来促进膀胱癌中的铁变态反应。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-27 DOI: 10.1038/s41417-024-00784-6

Changkun Liu, Zhuo Zou, Shengming Lu, Kun Jin, Ye Shen, Tianbao Huang, Weijian Li, Guangchen Zhou

{"title":"CircPKN2 promotes ferroptosis in bladder cancer by promoting the ubiquitination of Stearoyl-CoA Desaturase 1","authors":"Changkun Liu, Zhuo Zou, Shengming Lu, Kun Jin, Ye Shen, Tianbao Huang, Weijian Li, Guangchen Zhou","doi":"10.1038/s41417-024-00784-6","DOIUrl":"10.1038/s41417-024-00784-6","url":null,"abstract":"Bladder cancer (BC) is one of the most common malignancies in the male urinary system and currently lacks an optimal treatment strategy. To elucidate the pathogenic mechanisms of BC from the perspective of circular RNAs, we conducted this study. Building upon our previous research, a novel circRNA, circPKN2, captured our interest due to its significant downregulation in BC, and its close association with the prognosis of BC patients. Our research findings indicate that circPKN2 can inhibit the proliferation and migration of BC cells in vitro. Furthermore, we discovered that circPKN2 exerts its anti-cancer effects in BC by promoting ferroptosis. Mechanistic studies revealed that circPKN2 recruits STUB1 to facilitate the ubiquitination of SCD1, thereby suppressing the WNT pathway and promoting ferroptosis in BC. Additionally, our research unveiled the regulatory role of the splicing factor QKI in the biogenesis of circPKN2. Animal studies demonstrated that circPKN2 enhances ferroptosis in BC cells in vivo, inhibiting tumor growth and metastasis. The discovery of the anti-cancer factor circPKN2 holds promise for providing new therapeutic targets in the prevention and treatment of BC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1251-1265"},"PeriodicalIF":4.8,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157884","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

Hsa_circ_0007590/PTBP1 complex reprograms glucose metabolism by reducing the stability of m6A-modified PTEN mRNA in pancreatic ductal adenocarcinoma Hsa_circ_0007590/PTBP1 复合物通过降低胰腺导管腺癌中 m6A 修饰的 PTEN mRNA 的稳定性来重编葡萄糖代谢。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-27 DOI: 10.1038/s41417-024-00786-4

Dandan Zheng, Wenying Chen, Juanfei Peng, Xianxian Huang, Shineng Zhang, Yanyan Zhuang

{"title":"Hsa_circ_0007590/PTBP1 complex reprograms glucose metabolism by reducing the stability of m6A-modified PTEN mRNA in pancreatic ductal adenocarcinoma","authors":"Dandan Zheng, Wenying Chen, Juanfei Peng, Xianxian Huang, Shineng Zhang, Yanyan Zhuang","doi":"10.1038/s41417-024-00786-4","DOIUrl":"10.1038/s41417-024-00786-4","url":null,"abstract":"The role of circular RNAs (circRNAs) in glucose metabolism in pancreatic duct adenocarcinoma (PDAC) remains elusive. Through RNA sequencing of cells cultured under conditions of glucose deprivation, we identified hsa_circ_0007590. Sanger sequencing and RNase R and Act D treatments were performed to confirm the circular RNA features of hsa_circ_0007590. RNA in situ hybridization (RNA-ISH) and quantitative reverse transcription PCR (qRT-PCR) were used to estimate hsa_circ_0007590 expression in PDAC clinical specimens and cell lines. hsa_circ_0007590 expression was higher in PDAC patients and closely related to the clinicopathological characteristics of the disease. Cytoplasm‒nuclear fractionation and FISH assays demonstrated that hsa_circ_0007590 was located in the nucleus. Gain-of-function and loss-of-function assays were performed to assess the biological behaviors of PDAC cells. Seahorse XF assays were performed to validate the Warburg effect. hsa_circ_0007590 facilitated the proliferation, migration, and invasion of PDAC cells and promoted the Warburg effect. Mass spectrometry, RNA pulldown, RNA immunoprecipitation (RIP), RNA m6A quantification, m6A dot blot, MeRIP, and Western blotting were conducted to investigate the detailed mechanism through which hsa_circ_0007590 produces these effects. Mechanistically, hsa_circ_0007590 targeted PTBP1 and increased the expression of the m6A reader protein YTHDF2, leading to PTEN mRNA degradation and PI3K/AKT/mTOR pathway activation. Overall, hsa_circ_0007590, which targets PTBP1, reprograms glucose metabolism by attenuating the stability of m6A-modified PTEN mRNA and holds potential promise as a therapeutic target for PDAC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"1090-1102"},"PeriodicalIF":4.8,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157888","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

IGF2BP2-modified circular RNA circCHD7 promotes endometrial cancer progression via stabilizing PDGFRB and activating JAK/STAT signaling pathway IGF2BP2修饰的环状RNA circCHD7通过稳定PDGFRB和激活JAK/STAT信号通路促进子宫内膜癌的进展。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-22 DOI: 10.1038/s41417-024-00781-9

Rui Shi, Rong Zhao, Yan Shen, Sitian Wei, Tangansu Zhang, Jun Zhang, Wan Shu, Shuangshuang Cheng, Hua Teng, Hongbo Wang

{"title":"IGF2BP2-modified circular RNA circCHD7 promotes endometrial cancer progression via stabilizing PDGFRB and activating JAK/STAT signaling pathway","authors":"Rui Shi, Rong Zhao, Yan Shen, Sitian Wei, Tangansu Zhang, Jun Zhang, Wan Shu, Shuangshuang Cheng, Hua Teng, Hongbo Wang","doi":"10.1038/s41417-024-00781-9","DOIUrl":"10.1038/s41417-024-00781-9","url":null,"abstract":"Circular RNAs (circRNAs) represent a class of covalently closed, single-stranded RNAs and have been linked to cancer progression. N6-methyladenosine (m6A) methylation is a ubiquitous RNA modification in cancer cells. Increasing evidence suggests that m6A can mediate the effects of circRNAs in cancer biology. In contrast, the post-transcriptional systems of m6A and circRNA in the progression of endometrial cancer (EC) remain obscure. The current study identified a novel circRNA with m6A modification, hsa_circ_0084582 (circCHD7), which was upregulated in EC tissues. Functionally, circCHD7 was found to promote the proliferation of EC cells. Mechanistically, circCHD7 interacted with insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) to amplify its enrichment. Moreover, circCHD7 increased the mRNA stability of platelet-derived growth factor receptor beta (PDGFRB) in an m6A-dependent manner, thereby enhancing its expression. In addition, the circCHD7/IGF2BP2/PDGFRB axis activated the JAK/STAT signaling pathway and promoted EC cell proliferation. In conclusion, these findings provide new insights into the regulation of circRNA-mediated m6A modification, and the new “circCHD7-PDGFRB” model of regulation offers new perspectives on circCHD7 as a potential target for EC therapy.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1221-1236"},"PeriodicalIF":4.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00781-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080965","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

Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages 磷酸甘油酸突变酶 1 通过诱导免疫抑制性 M2 巨噬细胞促进乳腺癌的进展。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-15 DOI: 10.1038/s41417-024-00769-5

Dong Zhang, Min Wang, Shiya Ma, Min Liu, Wenwen Yu, Xiying Zhang, Ting Liu, Shaochuan Liu, Xiubao Ren, Qian Sun

{"title":"Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages","authors":"Dong Zhang, Min Wang, Shiya Ma, Min Liu, Wenwen Yu, Xiying Zhang, Ting Liu, Shaochuan Liu, Xiubao Ren, Qian Sun","doi":"10.1038/s41417-024-00769-5","DOIUrl":"10.1038/s41417-024-00769-5","url":null,"abstract":"Immunosuppressive tumor microenvironment (TME) contributes to tumor progression and causes major obstacles for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism while its role in remodeling TME remains unclear. In this study, we reported that PGAM1 suppression in breast cancer (BC) cells led to a decrease in M2 polarization, migration, and interleukin-10 (IL-10) production of macrophages. PGAM1 regulation on CCL2 expression was essential to macrophage recruitment, which further mediated by activating JAK-STAT pathway. Additionally, the CCL2/CCR2 axis was observed to participate in PGAM1-mediated immunosuppression via regulating PD-1 expression in macrophages. Combined targeting of PGAM1 and the CCL2/CCR2 axis led to a reduction in tumor growth in vivo. Furthermore, clinical validation in BC tissues indicated a positive correlation between PGAM1, CCL2 and macrophage infiltration. Our study provides novel insights into the induction of immunosuppressive TME by PGAM1 and propose a new strategy for combination therapies targeting PGAM1 and macrophages in BC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"1018-1033"},"PeriodicalIF":4.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943707","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

Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer Dickkopf-1（DKK1）能促进耐受性前列腺癌的生长和转移。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-13 DOI: 10.1038/s41417-024-00783-7

Letizia Rinella, Gloria Fiorentino, Mara Compagno, Cristina Grange, Massimo Cedrino, Francesca Marano, Ornella Bosco, Elena Vissio, Luisa Delsedime, Patrizia D’Amelio, Benedetta Bussolati, Emanuela Arvat, Maria Graziella Catalano

{"title":"Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer","authors":"Letizia Rinella, Gloria Fiorentino, Mara Compagno, Cristina Grange, Massimo Cedrino, Francesca Marano, Ornella Bosco, Elena Vissio, Luisa Delsedime, Patrizia D’Amelio, Benedetta Bussolati, Emanuela Arvat, Maria Graziella Catalano","doi":"10.1038/s41417-024-00783-7","DOIUrl":"10.1038/s41417-024-00783-7","url":null,"abstract":"Metastatic castration-resistant prostate cancer (mCRPC) is associated with a poor prognosis and remains an incurable fatal disease. Therefore, the identification of molecular markers involved in cancer progression is urgently needed to develop more-effective therapies. The present study investigated the role of the Wnt signaling modulator Dickkopf-1 (DKK1) in the growth and metastatic progression of mCRPC. DKK1 silencing through siRNA and deletion via CRISPR/Cas9 editing were performed in two different metastatic castration-resistant prostate cancer cell lines (PC3 and DU145). A xenograft tumor model was used to assess tumor growth and metastases. In in vitro experiments, both DKK1 silencing and deletion reduced cell growth and migration of both cell lines. DKK1 knockout clones (DKK1-KO) exhibited cell cycle arrest, tubulin reorganization, and modulation of tumor metastasis-associated genes. Furthermore, in DKK1-KO cells, E-cadherin re-expression and its membrane co-localization with β-catenin were observed, contributing to reduced migration; Cadherin-11, known to increase during epithelial-mesenchymal transition, was down-regulated in DKK1-KO cells. In the xenograft mouse model, DKK1 deletion not only reduced tumor growth but also inhibited the formation of lung metastases. In conclusion, our findings support the key role of DKK1 in the growth and metastatic dissemination of mCRPC, both in vitro and in vivo.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1266-1279"},"PeriodicalIF":4.8,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915940","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

Targeting KRASG12D mutation in non-small cell lung cancer: molecular mechanisms and therapeutic potential 针对非小细胞肺癌中的 KRASG12D 突变：分子机制和治疗潜力。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-11 DOI: 10.1038/s41417-024-00778-4

Yining Tang, Xi Pu, Xiao Yuan, Zhonghao Pang, Feng Li, Xu Wang

{"title":"Targeting KRASG12D mutation in non-small cell lung cancer: molecular mechanisms and therapeutic potential","authors":"Yining Tang, Xi Pu, Xiao Yuan, Zhonghao Pang, Feng Li, Xu Wang","doi":"10.1038/s41417-024-00778-4","DOIUrl":"10.1038/s41417-024-00778-4","url":null,"abstract":"Lung malignant tumors are a type of cancer with high incidence and mortality rates worldwide. Non-small cell lung cancer (NSCLC) accounts for over 80% of all lung malignant tumors, and most patients are diagnosed at advanced stages, leading to poor prognosis. Over the past decades, various oncogenic driver alterations associated with lung cancer have been identified, each of which can potentially serve as a therapeutic target. Rat sarcoma (RAS) genes are the most commonly mutated oncogenes in human cancers, with Kirsten rat sarcoma (KRAS) being the most common subtype. The role of KRAS oncogene in NSCLC is still not fully understood, and its impact on prognosis remains controversial. Despite the significant advancements in targeted therapy and immune checkpoint inhibitors (ICI) that have transformed the treatment landscape of advanced NSCLC in recent years, targeting KRAS (both directly and indirectly) remains challenging and is still under intensive research. In recent years, significant progress has been made in the development of targeted drugs targeting the NSCLC KRASG12C mutant subtype. However, research progress on target drugs for the more common KRASG12D subtype has been slow, and currently, no specific drugs have been approved for clinical use, and many questions remain to be answered, such as the mechanisms of resistance in this subtype of NSCLC, how to better utilize combination strategies with multiple treatment modalities, and whether KRASG12D inhibitors offer substantial efficacy in the treatment of advanced NSCLC patients.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"961-969"},"PeriodicalIF":4.8,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00778-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907945","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

TRIM58 downregulation maintains stemness via MYH9-GRK3-YAP axis activation in triple-negative breast cancer stem cells TRIM58 下调可通过激活三阴性乳腺癌干细胞中的 MYH9-GRK3-YAP 轴维持干性。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-07 DOI: 10.1038/s41417-024-00780-w

Xujun Li, Jing Jiang, Qian Wu, Tianzi You, Fan Yang

{"title":"TRIM58 downregulation maintains stemness via MYH9-GRK3-YAP axis activation in triple-negative breast cancer stem cells","authors":"Xujun Li, Jing Jiang, Qian Wu, Tianzi You, Fan Yang","doi":"10.1038/s41417-024-00780-w","DOIUrl":"10.1038/s41417-024-00780-w","url":null,"abstract":"TRIM58 is a member of the TRIM protein family, which possess with E3 ubiquitin ligase activities. Studies have revealed that low expression of TRIM58 plays key roles, has been implicated in the tumor progression of tumor formation due to its reduced expression. However, its role in regulating the stemness of breast cancer stem cells (CSCs) remains unexplored. Here, we found that TRIM58 was underexpressed in TNBC tissues and cells compared to adjacent mucosa tissue, and its downregulation was significantly associated with shorter survival. Overexpression of TRIM58 reduced the proportion of CD44 + /CD24- cells, upregulated differentiation genes, and inhibited stemness-related gene expression in TNBC CSCs. In vitro and in vivo experiments revealed that TRIM58 overexpression in CSCs suppressed tumor sphere formation and tumorigenic capacity. Co-IP results indicated direct interaction between TRIM58 and MYH9, with TRIM58 inducing MYH9 degradation via ubiquitination in differentiated cells. Label-free quantitative proteomics identified GRK3 and Hippo-YAP as downstream targets and signaling pathways of MYH9. TIMER database analysis, immunohistochemistry, western blotting, DNA-protein pulldown experiments, and dual luciferase reporter assays demonstrated that MYH9 regulated GRK3 transcriptional activation in CSCs. In conclusion, elevated TRIM58 expression in CSCs downregulates MYH9 protein levels by promoting ubiquitin-mediated degradation, thereby inhibiting downstream GRK3 transcription, inactivating the YAP stemness pathway, and ultimately promoting CSC differentiation.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1186-1200"},"PeriodicalIF":4.8,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875863","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

Editorial Expression of Concern: Herpes simplex virus thymidine kinase/ganciclovir–induced cell death is enhanced by co-expression of caspase-3 in ovarian carcinoma cells 社论表达的关切：卵巢癌细胞中，单纯疱疹病毒胸苷激酶/更昔洛韦诱导的细胞死亡因同时表达 Caspase-3 而增强。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-02 DOI: 10.1038/s41417-024-00777-5

I. A. McNeish, T. Tenev, S. Bell, M. Marani, G. Vassaux, N. Lemoine

引用次数: 0