Cellular Oncology最新文献

{"title":"Ferritinophagy induced ferroptosis in the management of cancer.","authors":"Yi-Chen Liu, Yi-Ting Gong, Qing-Yan Sun, Bei Wang, Yue Yan, Yi-Xu Chen, Li-Jun Zhang, Wei-Dong Zhang, Xin Luan","doi":"10.1007/s13402-023-00858-x","DOIUrl":"10.1007/s13402-023-00858-x","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis, a newly form of regulated cell death (RCD), is characterized by iron dyshomeostasis and unrestricted lipid peroxidation. Emerging evidence depicts a pivotal role for ferroptosis in driving some pathological processes, especially in cancer. Triggering ferroptosis can suppress tumor growth and induce an anti-tumor immune response, denoting the therapeutic promises for targeting ferroptosis in the management of cancer. As an autophagic phenomenon, ferritinophagy is critical to induce ferroptosis by degradation of ferritin to release intracellular free iron. Recently, a great deal of effort has gone into designing and developing anti-cancer strategies based on targeting ferritinophagy to induce ferroptosis.</p><p><strong>Conclusion: </strong>This review delineates the regulatory mechanism of ferritinophagy firstly and summarizes the role of ferritinophagy-induced ferroptosis in cancer. Moreover, the strategies targeting ferritinophagy to induce ferroptosis are highlighted to unveil the therapeutic value of ferritinophagy as a target to manage cancer. Finally, the future research directions on how to cope with the challenges in developing ferritinophagy promoters into clinical therapeutics are discussed.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"19-35"},"PeriodicalIF":6.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10592229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ONECUT3 blocks glycolytic metabolism and potentiates anti-PD-1 therapy in pancreatic cancer.","authors":"Peng-Cheng Chen, Yong Ning, Hui Li, Jin-Gen Su, Jiang-Bo Shen, Qing-Chun Feng, Shu-Heng Jiang, Pei-Dong Shi, Run-Sheng Guo","doi":"10.1007/s13402-023-00852-3","DOIUrl":"10.1007/s13402-023-00852-3","url":null,"abstract":"<p><strong>Background: </strong>Reprogramming glucose metabolism, also known as the Warburg effect (aerobic glycolysis), is a hallmark of cancers. Increased tumor glycolysis not only favors rapid cancer cell proliferation but reprograms the immune microenvironment to enable tumor progression. The transcriptional factor ONECUT3 plays key roles in the development of the liver and pancreas, however, limited is known about its oncogenic roles, particularly metabolic reprogramming.</p><p><strong>Methods: </strong>Immunohistochemistry and Western blotting are applied to determine the expression pattern of ONECUT3 and its clinical relevance in pancreatic ductal adenocarcinoma (PDAC). Knockdown and overexpression strategies are employed to determine the in vitro and in vivo functions of ONECUT3. Chromatin immunoprecipitation, luciferase reporter assay, and gene set enrichment analysis are used to decipher the molecular mechanisms.</p><p><strong>Results: </strong>The glycolytic metabolism is inversely associated with T-cell infiltration in PDAC. ONECUT3 is identified as a key regulator for PDAC glycolysis and CD8⁺ T-cell infiltration. Genetic silencing of ONECUT3 inhibits cell proliferation, promotes cell apoptosis, and reduces glycolytic metabolism as evidenced by glucose uptake, lactate production, and extracellular acidification rate. Opposite effects of ONECUT3 are observed in overexpression studies. ONECUT3 enhances aerobic glycolysis via transcriptional regulation of PDK1. Targeting ONECUT3 effectively suppresses tumor growth, increases CD8⁺ T-cell infiltration, and potentiates anti-PD-1 therapy in PDAC. Pharmacological inhibition of PDK1 also shows a synergistic effect with anti-PD-1 therapy. In clinical setting, ONECUT3 is closely associated with PDK1 expression and T-cell infiltration in PDAC and acts as an independent prognostic factor.</p><p><strong>Conclusions: </strong>Our study reveals a previous unprecedented regulatory role of ONECUT3 in PDAC glycolysis and provides in vivo evidence that increased glycolysis is linked to an immunosuppressive microenvironment. Moreover, targeting ONECUT3-PDK1 axis may serve as a promising therapeutic approach for the treatment of PDAC.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"81-96"},"PeriodicalIF":6.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of high level E2F in a RB1 proficient MYCN overexpressing chicken retinoblastoma model normalizes neoplastic behaviour.","authors":"Hanzhao Zhang, Dardan Konjusha, Nima Rafati, Tatsiana Tararuk, Finn Hallböök","doi":"10.1007/s13402-023-00863-0","DOIUrl":"10.1007/s13402-023-00863-0","url":null,"abstract":"<p><strong>Purpose: </strong>Retinoblastoma, a childhood cancer, is most frequently caused by bi-allelic inactivation of RB1 gene. However, other oncogenic mutations such as MYCN amplification can induce retinoblastoma with proficient RB1. Previously, we established RB1-proficient MYCN-overexpressing retinoblastoma models both in human organoids and chicken. Here, we investigate the regulatory events in MYCN-induced retinoblastoma carcinogenesis based on the model in chicken.</p><p><strong>Methods: </strong>MYCN transformed retinal cells in culture were obtained from in vivo MYCN electroporated chicken embryo retina. The expression profiles were analysed by RNA sequencing. Chemical treatments, qRT-PCR, flow cytometry, immunohisto- and immunocytochemistry and western blot were applied to study the properties and function of these cells.</p><p><strong>Results: </strong>The expression profile of MYCN-transformed retinal cells in culture showed cone photoreceptor progenitor signature and robustly increased levels of E2Fs. This expression profile was consistently observed in long-term culture. Chemical treatments confirmed RB1 proficiency in these cells. The cells were insensitive to p53 activation but inhibition of E2f efficiently induced cell cycle arrest followed by apoptosis.</p><p><strong>Conclusion: </strong>In conclusion, with proficient RB1, MYCN-induced high level of E2F expression dysregulates the cell cycle and contributes to retinoblastoma carcinogenesis. The increased level of E2f renders the cells to adopt a similar mechanistic phenotype to a RB1-deficient tumour.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"209-227"},"PeriodicalIF":6.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate score classification of hepatocellular carcinoma helps identify patients with tumors that respond to immune checkpoint blockade therapy.","authors":"Kai Jiang, Lili Zhu, Huizhen Huang, Liu Zheng, Zhuqing Wang, Xiaonan Kang","doi":"10.1007/s13402-023-00861-2","DOIUrl":"10.1007/s13402-023-00861-2","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatocellular carcinoma (HCC) responds poorly to immunotherapy, and the durable response rate is 10-20%. Here, we aim to characterize HCC classifications based on lactate genes to identify patients who may benefit from immunotherapy.</p><p><strong>Methods: </strong>Lactate-related genes were applied for HCC classification in the current study, and lactate Cluster 1 (LC1) and lactate Cluster 2 (LC2) were defined. Differential genes from LC1 and LC2 helped define the following lactate phenotype clusters: lactate phenotype Cluster 1 (LPC1), lactate phenotype Cluster 2 (LPC2) and lactate phenotype Cluster 3 (LPC3). Based on the cluster annotation, the lactate score was defined and analyzed to evaluate the immunotherapy response.</p><p><strong>Results: </strong>All the classified clusters were analyzed, and they showed different immune signatures. The survival rate of LPC3 was higher than that of LPC2 (LPC3 vs. LPC2, P = 0.027) and LPC1 (LPC3 vs. LPC1, P = 0.027). Then, the lactate score was annotated and confirmed to be effective in predicting responses to immune checkpoint blockade therapy.</p><p><strong>Conclusion: </strong>In the current study, we developed a classification system for HCC and defined the lactate score, which was validated to be partially effective in estimating responses among tumor patients.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"175-188"},"PeriodicalIF":6.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquilin-4 induces immune escape in gastric cancer by activating the notch signaling pathway.","authors":"Quan Jiang, Hao Chen, Shixin Zhou, Tao Zhu, Wenshuai Liu, Hao Wu, Yong Zhang, Fenglin Liu, Yihong Sun","doi":"10.1007/s13402-023-00869-8","DOIUrl":"10.1007/s13402-023-00869-8","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to investigate the role of ubiquilin-4 in predicting the immunotherapy response in gastric cancer.</p><p><strong>Methods: </strong>Retrospective RNA-sequencing and immunohistochemical analysis were performed for patients with gastric cancer who received programmed death-1 blockade therapy after recurrence. Multiplex immunohistochemistry identified immune cell types in gastric cancer tissues. We used immunocompetent 615 mice and immunodeficient nude mice to perform tumorigenic experiments.</p><p><strong>Results: </strong>Ubiquilin-4 expression was significantly higher in responders (p < 0.05, false discovery rate > 2.5) and showed slight superiority over programmed death ligand 1 in predicting programmed death-1 inhibitor therapy response (area under the curve: 87.08 vs. 72.50). Ubiquilin-4-high patients exhibited increased CD4⁺ and CD8⁺ T cells, T follicular helper cells, monocytes, and macrophages. Ubiquilin-4-overexpressed mouse forestomach carcinoma cells showed significantly enhanced growth in immunocompetent mice but not in immunodeficient mice. Upregulation or downregulation of ubiquilin-4 synergistically affected programmed death ligand 1 at the protein and messenger RNA levels. Functional enrichment analysis revealed significant enrichment of the Notch, JAK-STAT, and WNT signaling pathways in ubiquilin-4-high gastric cancers. Ubiquilin-4 promoted Numb degaration, activating the Notch signaling pathway and upregulating programmed death ligand 1.</p><p><strong>Conclusions: </strong>Ubiquilin-4 may contribute to immune escape in gastric cancer by upregulating programmed death ligand 1 expression in tumor cells through Notch signaling activation. Thus, ubiquilin-4 could serve as a predictive marker for programmed death ligand 1 inhibitor therapy response in gastric cancer.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"303-319"},"PeriodicalIF":6.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10591214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vimentin promotes glioma progression and maintains glioma cell resistance to oxidative phosphorylation inhibition.","authors":"Yu'e Liu, Shu Zhao, Yi Chen, Wencong Ma, Shiping Lu, Le He, Jie Chen, Xi Chen, Xiaoling Zhang, Yufeng Shi, Xuan Jiang, Kaijun Zhao","doi":"10.1007/s13402-023-00844-3","DOIUrl":"10.1007/s13402-023-00844-3","url":null,"abstract":"<p><strong>Purpose: </strong>Glioma has been demonstrated as one of the most malignant intracranial tumors and currently there is no effective treatment. Based on our previous RNA-sequencing data for oxidative phosphorylation (OXPHOS)-inhibition resistant and OXPHOS-inhibition sensitive cancer cells, we found that vimentin (VIM) is highly expressed in the OXPHOS-inhibition resistant cancer cells, especially in glioma cancer cells. Further study of VIM in the literature indicates that it plays important roles in cancer progression, immunotherapy suppression, cancer stemness and drug resistance. However, its role in glioma remains elusive. This study aims to decipher the role of VIM in glioma, especially its role in OXPHOS-inhibition sensitivity, which may provide a promising therapeutic target for glioma treatment.</p><p><strong>Methods: </strong>The expression of VIM in glioma and the normal tissue has been obtained from The Cancer Genome Atlas (TCGA) database, and further validated in Human Protein Atlas (HPA) and Chinese Glioma Genome Atlas (CGGA). And the single-cell sequencing data was obtained from TISCH2. The immune infiltration was calculated via Tumor Immune Estimation Resource (TIMER), Estimation of Stromal and Immune Cells in Malignant Tumors using Expression Data (ESTIMATE) and ssGSEA, and the Immunophenoscore (IPS) was calculated via R package. The differentiated expressed genes were analyzed including GO/KEGG and Gene Set Enrichment Analysis (GSEA) between the VIM-high and -low groups. The methylation of VIM was checked at the EWAS and Methsurv. The correlation between VIM expression and cancer stemness was obtained from SangerBox. We also employed DepMap data and verified the role of VIM by knocking down it in VIM-high glioma cell and over-expressing it in VIM-low glioma cells to check the cell viability.</p><p><strong>Results: </strong>Vim is highly expressed in the glioma patients compared to normal samples and its high expression negatively correlates with patients' survival. The DNA methylation in VIM promoters in glioma patients is lower than that in the normal samples. High VIM expression positively correlates with the immune infiltration and tumor progression. Furthermore, Vim is expressed high in the OXPHOS-inhibition glioma cancer cells and low in the OXPHOS-inhibition sensitive ones and its expression maintains the OXPHOS-inhibition resistance.</p><p><strong>Conclusions: </strong>In conclusion, we comprehensively deciphered the role of VIM in the progression of glioma and its clinical outcomes. Thus provide new insights into targeting VIM in glioma cancer immunotherapy in combination with the current treatment.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1791-1806"},"PeriodicalIF":6.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10111042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of miR-146b by N6-methyladenosine modification remodels tumor-associated macrophages and enhances anti-PD-1 therapy in colorectal cancer.","authors":"Shuying He, Wen Song, Shudan Cui, Jiating Li, Yonghong Jiang, Xueqing Chen, Liang Peng","doi":"10.1007/s13402-023-00839-0","DOIUrl":"10.1007/s13402-023-00839-0","url":null,"abstract":"<p><strong>Purpose: </strong>MicroRNA-146b (miR-146b) alleviates experimental colitis in mice by mediating macrophage polarization and the release of inflammatory factors. Our goals were to evaluate the antitumor efficacy of miR-146b in colorectal cancer (CRC) and to investigate the underlying mechanisms.</p><p><strong>Methods: </strong>We used murine models of CRC to evaluate whether miR-146b influenced the progression of tumors independent of tumor-associated macrophages (TAMs). RNA immunoprecipitation, N6-methyladenosine (m⁶A) RNA immunoprecipitation and in vitro pri-miRNA processing assays were conducted to examine whether m⁶A mediates the maturation of pri-miR-146b/miR-146b. In a series of in vitro and in vivo experiments, we further defined the molecular mechanisms of methyltransferase-like 3 (METTL3)/miR-146b-mediated antitumor immunity and its efficacy in combination with anti-PD-1 immunotherapy.</p><p><strong>Results: </strong>We found that miR-146b deletion supported tumor progression by increasing the number of alternatively activated (M2) TAMs. Mechanistically, the m⁶A-related \"writer\" protein METTL3 and \"reader\" protein HNRNPA2B1 controlled miR-146b maturation by regulating the m⁶A modification region of pri-miR-146b. Furthermore, miR-146b deletion promoted the polarization of M2-TAMs by enhancing phosphoinositide 3-kinase (PI3K)/AKT signaling, and this effect was mediated by the class IA PI3K catalytic subunit p110β, which reduced T cell infiltration, aggravated immunosuppression and ultimately promoted tumor progression. METTL3 knockdown or miR-146b deletion induced programmed death ligand 1 (PD-L1) production via the p110β/PI3K/AKT pathway in TAMs and consequently augmented the antitumor activity of anti-PD-1 immunotherapy.</p><p><strong>Conclusions: </strong>The maturation of pri-miR-146b is m⁶A-dependent, and miR-146b deletion-mediated TAM differentiation promotes the development of CRC by activating the PI3K/AKT pathway, which induces upregulation of PD-L1 expression, inhibits T cell infiltration into the TME and enhances the antitumor activity of anti-PD-1 immunotherapy. The findings reveal that targeting miR-146b can serve as an adjuvant to anti-PD-1 immunotherapy.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1731-1746"},"PeriodicalIF":6.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10128479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA CCAT2 promotes malignant progression of metastatic gastric cancer through regulating CD44 alternative splicing.","authors":"Huan Deng, Jingwang Gao, Bo Cao, Ziyu Qiu, Tian Li, Ruiyang Zhao, Hanghang Li, Bo Wei","doi":"10.1007/s13402-023-00835-4","DOIUrl":"10.1007/s13402-023-00835-4","url":null,"abstract":"<p><strong>Objective: </strong>Gastric cancer (GC) is one of the most malignant tumors worldwide. Thus, it is necessary to explore the underlying mechanisms of GC progression and develop novel therapeutic regimens. Long non-coding RNAs (lncRNAs) have been demonstrated to be abnormally expressed and regulate the malignant behaviors of cancer cells. Our previous research demonstrated that lncRNA colon cancer-associated transcript 2 (CCAT2) has potential value for GC diagnosis and discrimination. However, the functional mechanisms of lncRNA CCAT2 in GC development remain to be explored.</p><p><strong>Methods: </strong>GC and normal adjacent tissues were collected to detect the expression of lncRNA CCAT2, ESRP1 and CD44 in clinical specimens and their clinical significance for GC patients. Cell counting kit-8, wound healing and transwell assays were conducted to investigate the malignant behaviors in vitro. The generation of nude mouse xenografts by subcutaneous, intraperitoneal and tail vein injection was performed to examine GC growth and metastasis in vivo. Co-immunoprecipitation, RNA-binding protein pull-down assay and fluorescence in situ hybridization were performed to reveal the binding relationships between ESRP1 and CD44.</p><p><strong>Results: </strong>In the present study, lncRNA CCAT2 was overexpressed in GC tissues compared to adjacent normal tissues and correlated with short survival time of patients. lncRNA CCAT2 promoted the proliferation, migration and invasion of GC cells. Its overexpression modulates alternative splicing of Cluster of differentiation 44 (CD44) variants and facilitates the conversion from the standard form to variable CD44 isoform 6 (CD44v6). Mechanistically, lncRNA CCAT2 upregulated CD44v6 expression by binding to epithelial splicing regulatory protein 1 (ESRP1), which subsequently mediates CD44 alternative splicing. The oncogenic role of the lncRNA CCAT2/ESRP1/CD44 axis in the promotion of malignant behaviors was verified by both in vivo and in vitro experiments.</p><p><strong>Conclusions: </strong>Our findings identified a novel mechanism by which lncRNA CCAT2, as a type of protein-binding RNA, regulates alternative splicing of CD44 and promotes GC progression. This axis may become an effective target for clinical diagnosis and treatment.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1675-1690"},"PeriodicalIF":6.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10054524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-4739 promotes epithelial-mesenchymal transition and angiogenesis in \"driver gene-negative\" non-small cell lung cancer via activating the Wnt/β-catenin signaling.","authors":"Wenjian Cen, Qin Yan, Wenpeng Zhou, Minjie Mao, Qitao Huang, Yaobin Lin, Neng Jiang","doi":"10.1007/s13402-023-00848-z","DOIUrl":"10.1007/s13402-023-00848-z","url":null,"abstract":"<p><strong>Purpose: </strong>\"Driver gene-negative\" non-small cell lung cancer (NSCLC) currently has no approved targeted drug, due to the lack of common actionable driver molecules. Even though miRNAs play crucial roles in various malignancies, their roles in \"driver gene-negative\" NSCLC keep unclear.</p><p><strong>Methods: </strong>miRNA expression microarrays were utilized to screen miRNAs associated with \"driver gene-negative\" NSCLC malignant progression. Quantitative real-time PCR (RT-qPCR) and in situ hybridization (ISH) were employed to validate the expression of miR-4739, and its correlation with clinicopathological characteristics was analyzed in tumor specimens using univariate and multivariate analyses. The biological functions and underlying mechanisms of miR-4739 were investigated both in vitro and in vivo.</p><p><strong>Results: </strong>our research demonstrated, for the first time, that miR-4739 was substantially increased in \"driver gene-negative\" NSCLC tumor tissues and cell lines, and overexpression of miR-4739 was related to clinical staging, metastasis, and unfavorable outcomes. Functional experiments discovered that miR-4739 dramatically enhanced tumor cell proliferation, migration, and metastasis by promoting the epithelial-to-mesenchymal transition (EMT). Meanwhile, miR-4739 can be transported from cancer cells to the site of vascular epithelial cells through exosomes, consequently facilitating the proliferation and migration of vascular epithelial cells and inducing angiogenesis. Mechanistically, miR-4739 can activate Wnt/β-catenin signaling both in tumor cells and vascular epithelial cells by targeting Wnt/β-catenin signaling antagonists APC2 and DKK3, respectively.</p><p><strong>Conclusion: </strong>Our work identifies a valuable oncogene, miR-4739, that accelerates malignant progression in \"driver gene-negative\" NSCLC and serves as a potential therapeutic target for this group of tumors.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1821-1835"},"PeriodicalIF":6.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9873703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modulation of ferroptosis in cancer: Identifying epigenetic targets for novel anticancer therapy.","authors":"Jaewang Lee, Jong-Lyel Roh","doi":"10.1007/s13402-023-00840-7","DOIUrl":"10.1007/s13402-023-00840-7","url":null,"abstract":"<p><p>Ferroptosis is a newly recognized form of oxidative-regulated cell death resulting from iron-mediated lipid peroxidation accumulation. Radical-trapping antioxidant systems can eliminate these oxidized lipids and prevent disrupting the integrity of cell membranes. Epigenetic modifications can regulate ferroptosis by altering gene expression or cell phenotype without permanent sequence changes. These mechanisms include DNA methylation, histone modifications, RNA modifications, and noncoding RNAs. Epigenetic alterations in cancer can control the expression of ferroptosis regulators or related pathways, leading to changes in cell sensitivity to ferroptosis inducers or cancer progression. Epigenetic alterations in cancer are influenced by a wide range of cancer hallmarks, contributing to therapeutic resistance. Targeting epigenetic alterations is a promising approach to overcoming cancer resilience. However, the exact mechanisms involved in different types of cancer remain unresolved. Discovering more ferroptosis-associated epigenetic targets and interventions can help overcome current barriers in anticancer therapy. Many papers on epigenetic modifications of ferroptosis have been continuously published, making it essential to summarize the current state-of-the-art in the epigenetic regulation of ferroptosis in human cancer.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1605-1623"},"PeriodicalIF":6.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9774597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}