Molecular Oncology最新文献

{"title":"CRISPR targeting of FOXL2 c.402C>G mutation reduces malignant phenotype in granulosa tumor cells and identifies anti-tumoral compounds.","authors":"Sandra Amarilla-Quintana, Paloma Navarro, Iván Hernández, Alejandra Ramos, Ana Montero-Calle, Pablo Cabezas-Sainz, Maria J Barrero, Diego Megías, Borja Vilaplana-Martí, Carolina Epifano, Déborah Gómez-Dominguez, Sara Monzón, Isabel Cuesta, Laura Sánchez, Rodrigo Barderas, Jesús García-Donas, Alberto Martín, Ignacio Pérez de Castro","doi":"10.1002/1878-0261.13799","DOIUrl":"https://doi.org/10.1002/1878-0261.13799","url":null,"abstract":"<p><p>Forkhead box L2 (FOXL2) encodes a transcription factor essential for sex determination, and ovary development and maintenance. Mutations in this gene are implicated in syndromes involving premature ovarian failure and granulosa cell tumors (GCTs). This rare cancer accounts for less than 5% of diagnosed ovarian cancers and is causally associated with the FOXL2 c.402C>G, p.C134W mutation in 97% of the adult cases (AGCTs). In this study, we employed CRISPR technology to specifically eliminate the FOXL2 c.402C>G mutation in granulosa tumor cells. Our results show that this Cas9-mediated strategy selectively targets the mutation without affecting the wild-type allele. Granulosa cells lacking FOXL2 c.402C>G exhibit a reduced malignant phenotype, with significant changes in cell proliferation and invasion. Furthermore, these modified cells are more susceptible to dasatinib and ketoconazole. Transcriptomic and proteomic analyses reveal that CRISPR-modified granulosa tumor cells shift their expression profiles towards a wild-type-like phenotype. Additionally, this altered expression signature has led to the identification of new compounds with antiproliferative and pro-apoptotic effects on granulosa tumor cells. Our findings demonstrate the potential of CRISPR technology for the specific targeting and elimination of a mutation causing GCTs, highlighting its therapeutic promise for treating this rare ovarian cancer.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951890","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":"Polyfunctional CD8⁺CD226⁺RUNX2^hi effector T cells are diminished in advanced stages of chronic lymphocytic leukemia.","authors":"Maryam Rezaeifar, Shima Shahbaz, Anthea C Peters, Spencer B Gibson, Shokrollah Elahi","doi":"10.1002/1878-0261.13793","DOIUrl":"https://doi.org/10.1002/1878-0261.13793","url":null,"abstract":"<p><p>CD8⁺ T cells, a subset of T cells identified by the surface glycoprotein CD8, particularly those expressing the co-stimulatory molecule CD226, play a crucial role in the immune response to malignancies. However, their role in chronic lymphocytic leukemia (CLL), an immunosuppressive disease, has not yet been explored. We studied 64 CLL patients and 25 age- and sex-matched healthy controls (HCs). We analyzed the proportion of CD226-expressing cells among different CD8⁺ T cell subsets (including naïve, central memory, effector memory, and effectors) in CLL patients, stratified by Rai stage and immunoglobulin heavy-chain variable region gene (IgHV) mutation status. Additionally, we compared the effector functions of CD8⁺CD226⁺ cells and their CD226^- counterparts. We also quantified cytokine and chemokine levels in the plasma of CLL and HCs. Furthermore, we reanalyzed the publicly available bulk RNA-seq on CD226⁺ and CD226^-CD8⁺ T cells. Finally, we evaluated the impact of elevated cytokines/chemokines on CD226 expression. Our results showed that CD226-expressing cells were significantly decreased within the effector memory and effector CD8⁺ T cell subsets in CLL patients with advanced Rai stages and unmutated IgHV, a marker of poor prognosis. These cells displayed robust effector functions, including cytokine production, cytolytic activity, degranulation, proliferation, and migration capacity. In contrast, CD8⁺CD226^- T cells displayed an exhausted phenotype with reduced Runt-related transcription factor 2 (RUNX2) expression. Elevated levels of interleukin-6 (IL-6) and macrophage inflammatory protein-1 beta (MIP-1β) were inversely correlated with the frequency of CD8⁺CD226⁺ T cells and may contribute to the downregulation of CD226, possibly leading to T cell dysfunction in CLL. Our findings highlight the critical role of CD8⁺CD226⁺RUNX2^hi T cells in CLL and suggest that their reduction is associated with disease progression and poor clinical outcomes. This study also underscores the potential of targeting IL-6 and MIP-1β to preserve polyfunctional CD8⁺CD226⁺ T cells as a promising immunotherapy strategy.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951231","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":"Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.","authors":"Mariona Chicón-Bosch, Sara Sánchez-Serra, Marta Rosàs-Lapeña, Nicolás Costa-Fraga, Judit Besalú-Velázquez, Janet Illa-Bernadí, Silvia Mateo-Lozano, Florencia Cidre-Aranaz, Thomas G P Grünewald, Ángel Díaz-Lagares, Roser Lopez-Alemany, Òscar M Tirado","doi":"10.1002/1878-0261.13788","DOIUrl":"https://doi.org/10.1002/1878-0261.13788","url":null,"abstract":"<p><p>Ewing sarcoma (EWS) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients with metastasis at diagnosis. Mechanisms leading to metastasis remain poorly understood. To deepen our knowledge on EWS progression, we have profiled tumors and metastases from a spontaneous metastasis mouse model using a multi-omics approach. Combining transcriptomics, proteomics, and methylomics analyses, we identified signaling cascades and candidate genes enriched in metastases that could be modulating aggressiveness in EWS. Phenotypical validation of two of these candidates, cyclic AMP-responsive element-binding protein 1 (CREB1) and lipoxygenase homology domain-containing protein 1 (LOXHD1), showed an association with migration and clonogenic abilities. Moreover, previously described CREB1 downstream targets were present amongst the metastatic-enriched results. Combining the different omics datasets, we identified FYVE, RhoGEF, and PH domain-containing protein 4 (FGD4) as a CREB1 target interconnecting the different EWS biological layers (RNA, protein and methylation status) and whose high expression is associated with worse clinical outcome. Further studies will provide insight into EWS metastasis mechanisms and ultimately improve survival rates for EWS patients.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932279","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":"Detection rate for ESR1 mutations is higher in circulating-tumor-cell-derived genomic DNA than in paired plasma cell-free DNA samples as revealed by ddPCR.","authors":"Stavroula Smilkou, Aliki Ntzifa, Victoria Tserpeli, Ioanna Balgkouranidou, Alkistis Papatheodoridi, Evangelia Razis, Helena Linardou, Christos Papadimitriou, Amanda Psyrri, Flora Zagouri, Stylianos Kakolyris, Evi Lianidou","doi":"10.1002/1878-0261.13787","DOIUrl":"https://doi.org/10.1002/1878-0261.13787","url":null,"abstract":"<p><p>Plasma cell-free DNA (cfDNA) analysis to track estrogen receptor 1 (ESR1) mutations is highly beneficial for the identification of tumor molecular dynamics and the improvement of personalized treatments for patients with metastatic breast cancer (MBC). Plasma-cfDNA is, up to now, the most frequent liquid biopsy analyte used to evaluate ESR1 mutational status. Circulating tumor cell (CTC) enumeration and molecular characterization analysis provides important clinical information in patients with MBC. In this study, we investigated whether analysis of CTCs and circulating tumor DNA (ctDNA) provide similar or complementary information for the analysis of ESR1 mutations. We analyzed both plasma-cfDNA (n = 90) and paired CTC-derived genomic DNA (gDNA; n = 42) from 90 MBC patients for seven ESR1 mutations. Eight out of 90 (8.9%) plasma-cfDNA samples tested using the ddPLEX Mutation Detection Assay (Bio-Rad, Hercules, CA, USA), were found positive for one ESR1 mutation, whereas 11/42 (26.2%) CTC-derived gDNA samples were found positive for at least one ESR1 mutation. Direct comparison of paired samples (n = 42) revealed that the ESR1 mutation rate was higher in CTC-derived gDNA (11/42, 26.2%) than in plasma-cfDNA (6/42, 14.3%) samples. Our results, using this highly sensitive ddPLEX assay, reveal a higher percentage of mutations in CTC-derived gDNAs than in paired ctDNA in patients with MBC. CTC-derived gDNA analysis should be further evaluated as an important and complementary tool to ctDNA for identifying patients with ESR1 mutations and for guiding individualized therapy.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927618","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":"KMT2A degradation is observed in decitabine-responsive acute lymphoblastic leukemia cells.","authors":"Luisa Brock, Lina Benzien, Sandra Lange, Maja Huehns, Alexandra Runge, Catrin Roolf, Anett Sekora, Gudrun Knuebel, Hugo Murua Escobar, Christian Junghanss, Anna Richter","doi":"10.1002/1878-0261.13792","DOIUrl":"https://doi.org/10.1002/1878-0261.13792","url":null,"abstract":"<p><p>Hypermethylation of tumor suppressor genes is a hallmark of leukemia. The hypomethylating agent decitabine covalently binds, and degrades DNA (cytosine-5)-methyltransferase 1 (DNMT1). Structural similarities within DNA-binding domains of DNMT1, and the leukemic driver histone-lysine N-methyltransferase 2A (KMT2A) suggest that decitabine might also affect the latter. In acute lymphoblastic leukemia (ALL) cell lines, and xenograft models, we observed increased DNMT1, and KMT2A expression in response to decitabine-induced demethylation. Strikingly, KMT2A protein expression was diminished in all cell lines that experienced DNMT1 degradation. Moreover, only cells with reduced KMT2A protein levels showed biological effects following decitabine treatment. KMT2A wild-type, and rearranged cells were locked in G2 and G1 cell cycle phases, respectively, likely due to p27/p16 activation. Primary sample gene expression profiling confirmed different patterns between KMT2A wild-type, and translocated cells. This newly discovered decitabine mode of action via KMT2A degradation evokes anti-leukemic activity in adult ALL cells, and can act synergistically with menin inhibition. Following the successful clinical implementation of decitabine for acute myeloid leukemia, the drug should be considered a potential promising addition to the therapeutic portfolio for ALL as well.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927634","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":"Targeted metabolomics reveals novel diagnostic biomarkers for colorectal cancer.","authors":"Zuojian Hu, Fenglin Shen, Yang Liu, Ziqing Zhong, Yongling Chen, Zhiyuan Xia, Cuiju Mo, Hongxiu Yu","doi":"10.1002/1878-0261.13791","DOIUrl":"https://doi.org/10.1002/1878-0261.13791","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a prevalent malignant tumor worldwide, with a high mortality rate due to its complex etiology and limited early screening techniques. This study aimed to identify potential biomarkers for early detection of CRC utilizing targeted metabolite profiling of platelet-rich plasma (PRP). Based on multiple reaction monitoring (MRM) mode, liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis identified metabolites in PRP collected from patients with CRC (n = 70) and healthy controls (n = 30). A total of 302 metabolites were identified and quantified in this study, including various categories such as lipids, lipid mediators, amino acids, and derivatives, organic acids and derivatives, nucleotides and derivatives, alkaloids, carbohydrates, vitamins and derivatives, and others. The differential analysis revealed that five carbohydrates and organic acids (lactose, glycerol-3-phosphate, 2-hydroxyglutaric acid, isocitric acid, and citric acid) involved in the carbohydrate metabolism pathway displayed consistent upregulation within PRP derived from patients with CRC. To further validate the abundance of differential metabolites, 10 pairs of CRC tissues, adjacent tissues, and matched PRP were collected. Ultimately, five carbohydrate metabolites were validated in PRP, and compared with carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA199), the five carbohydrate metabolites significantly improved the specificity of differentiating patients with CRC from healthy controls. Furthermore, the diagnostic efficacy of the combined five-carbohydrate metabolite panel was superior to that of individual metabolites, CEA and CA199. The sensitivity, specificity, and AUC of the metabolite panel in distinguishing patients with CRC from healthy controls were 90.00%, 96.67%, and 0.961 (95% CI 0.922-0.998), respectively. Collectively, metabolomics was used to identify and validate differential metabolites in the PRP of CRC, which may serve as potential early screening markers for patients with CRC.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927635","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":"Platelet-activating factor: a potential therapeutic target to improve cancer immunotherapy.","authors":"Qi Yan, Hemn Mohammadpour","doi":"10.1002/1878-0261.13758","DOIUrl":"10.1002/1878-0261.13758","url":null,"abstract":"<p><p>The tumor microenvironment (TME) fosters cancer progression by supporting the differentiation and proliferation of myeloid-derived suppressor cells (MDSCs), which play a critical role in suppressing immune responses and facilitating tumor growth. Recent findings by Dahal et al. reveal that platelet-activating factor (PAF), a lipid mediator elevated in the TME, contributes to the differentiation of neutrophils into immunosuppressive neutrophils. They showed that inhibiting PAF signaling reduces MDSC-mediated immunosuppression, thereby enhancing cytotoxic T-cell activity. This approach may improve cancer immunotherapy outcomes, particularly when combined with checkpoint blockade therapies, suggesting a promising avenue for therapeutic development.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"11-14"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667842","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":"Patient-derived acellular ascites fluid affects drug responses in ovarian cancer cell lines through the activation of key signalling pathways.","authors":"Katharina Bischof, Andrea Cremaschi, Lena Eroukhmanoff, Johannes Landskron, Lise-Lotte Flage-Larsen, Alexandra Gade, Line Bjørge, Alfonso Urbanucci, Kjetil Taskén","doi":"10.1002/1878-0261.13726","DOIUrl":"10.1002/1878-0261.13726","url":null,"abstract":"<p><p>Malignant ascites is commonly produced in advanced epithelial ovarian cancer (EOC) and serves as unique microenvironment for tumour cells. Acellular ascites fluid (AAF) is rich in signalling molecules and has been proposed to play a role in the induction of chemoresistance. Through in vitro testing of drug sensitivity and by assessing intracellular phosphorylation status in response to mono- and combination treatment of five EOC cell lines after incubation with AAFs derived from 20 different patients, we investigated the chemoresistance-inducing potential of ascites. We show that the addition of AAFs to the culture media of EOC cell lines has the potential to induce resistance to standard-of-care drugs (SCDs). We also show that AAFs induce time- and concentration-dependent activation of downstream signalling to signal transducer and activator of transcription 3 (STAT3), and concomitantly altered phosphorylation of mitogen-activated protein kinase kinase (MEK), phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) and nuclear factor NF-kappa-B (NFκB). Antibodies targeting the interleukin-6 receptor (IL6R) effectively blocked phosphorylation of STAT3 and STAT1. Treatments with SCDs were effective in reducing cell viability in only a third of 30 clinically relevant conditions examined, defined as combinations of drugs, different cell lines and AAFs. Combinations of SCDs and novel therapeutics such as trametinib, fludarabine or rapamycin were superior in another third. Notably, we could nominate effective treatment combinations in almost all conditions except in 4 out of 30 conditions, in which trametinib or fludarabine showed higher efficacy alone. Taken together, our study underscores the importance of the molecular characterisation of individual patients' AAFs and the impact on treatment resistance as providing clinically meaningful information for future precision treatment approaches in EOC.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"81-98"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154595","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":"Thioredoxin-interacting protein (TXNIP) is a substrate of the NEDD4-like E3 ubiquitin-protein ligase WWP1 in cellular redox state regulation of acute myeloid leukemia cells.","authors":"Sara Giovannini, Yanan Li, Rosalba Pecorari, Claudia Fierro, Claudia Fiorilli, Federica Corigliano, Valeria Moriconi, Ji Zhou, Anna De Antoni, Artem Smirnov, Sara Rinalducci, Anna Maria Timperio, Massimiliano Agostini, Jinping Zhang, Yufang Shi, Eleonora Candi, Gerry Melino, Francesca Bernassola","doi":"10.1002/1878-0261.13722","DOIUrl":"10.1002/1878-0261.13722","url":null,"abstract":"<p><p>The HECT-type E3 ubiquitin WWP1 (also known as NEDD4-like E3 ubiquitin-protein ligase WWP1) acts as an oncogenic factor in acute myeloid leukemia (AML) cells. WWP1 overexpression in AML confers a proliferative advantage to leukemic blasts (abnormal immature white blood cells) and counteracts apoptotic cell death and differentiation. In an effort to elucidate the molecular basis of WWP1 oncogenic activities, we identified WWP1 as a previously unknown negative regulator of thioredoxin-interacting protein (TXNIP)-mediated reactive oxygen species (ROS) production in AML cells. TXNIP inhibits the disulfide reductase enzymatic activity of thioredoxin (Trx), impairing its antioxidant function and, ultimately, leading to the disruption of cellular redox homeostasis. In addition, TXNIP restricts cell growth and survival by blocking glucose uptake and metabolism. Here, we found that WWP1 directly interacts with TXNIP, thus promoting its ubiquitin-dependent proteasomal proteolysis. As a result, accumulation of TXNIP in response to WWP1 inactivation in AML blasts reduces Trx activity and increases ROS production, hence inducing cellular oxidative stress. Increased ROS generation in WWP1-depleted cells culminates in DNA strand breaks and subsequent apoptosis. Coherently with TXNIP stabilization following WWP1 inactivation, we also observed an impairment of both glucose up-take and consumption. Hence, a contribution to the increased cell death observed in WWP1-depleted cells also possibly arises from the attenuation of glucose up-take and glycolytic flux resulting from TXNIP accumulation. Future studies are needed to establish whether TXNIP-dependent deregulation of redox homeostasis in WWP1-overexpressing blasts may affect the response of leukemic cells to chemotherapeutic drugs.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"133-150"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372251","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":"RETRACTION: Targeting MYCN IRES in MYCN-amplified Neuroblastoma With Mir-375 Inhibits Tumor Growth and Sensitizes Tumor Cells to Radiation.","authors":"","doi":"10.1002/1878-0261.13775","DOIUrl":"10.1002/1878-0261.13775","url":null,"abstract":"<p><strong>Retraction: </strong>H. Zhang, T. Liu, S. Yi, L. Gu, and M. Zhou, \"Targeting MYCN IRES in MYCN-amplified Neuroblastoma With Mir-375 Inhibits Tumor Growth and Sensitizes Tumor Cells to Radiation,\" Molecular Oncology 9, no. 7 (2015): 1301-1311, https://doi.org/10.1016/j.molonc.2015.03.005. The above article, published online on 24 March 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Kevin Ryan; FEBS Press; and John Wiley & Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate image section duplications within the article (Figure 5B) and between this (Figures 3B and 4B) and another article published by the same group of authors in a different scientific context. The authors were unable to provide a satisfactory explanation and the original raw data, which has led the editors to lose confidence in the data presented. Therefore, the editors consider the conclusions substantially compromised and are retracting the paper.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"261"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770612","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}