Cancer Cell International最新文献

{"title":"MicroRNAome profiling of breast cancer unveils hsa-miR-5683 as a tumor suppressor microRNA predicting favorable clinical outcome.","authors":"Bushra Yasin Abohalawa, Hibah Shaath, Ramesh Elango, Radhakrishnan Vishnubalaji, Sameera Rashid, Reem Al-Sarraf, Mohammed Akhtar, Nehad M Alajez","doi":"10.1186/s12935-024-03550-8","DOIUrl":"10.1186/s12935-024-03550-8","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is a heterogeneous disease with diverse molecular subtypes, underscoring a better understanding of its molecular features and underlying regulatory mechanisms. Therefore, identifying novel prognostic biomarkers and therapeutic targets is crucial for advancing the current standard of care for breast cancer patients.</p><p><strong>Methods: </strong>Ninety-six formalin-fixed paraffin-embedded (FFPE) breast cancer samples underwent miRNAome profiling using QIAseq microRNA library kit and sequencing on Illumina platform. Mature miRNA quantification was conducted using CLC Genomics Workbench v21.0.5, while Relapse-free survival (RFS) analysis was conducted using RStudio 2023.09.1. Gain-of-function studies were conducted using miRNA mimics, while the effects of miRNA exogenous expression on cancer hallmark were assessed using 2-dimentional (2D) proliferation assay, three-dimensional (3D) organotypic culture, and live-dead staining. TargetScan database and Ingenuity Pathway Analysis (IPA) were used for miRNA target identification.</p><p><strong>Results: </strong>Hierarchical clustering based on miRNA expression revealed distinct patterns in relation to PAM50 classification and identified miRNAs panels associated with luminal, HER2, and basal subtypes. hsa-miR-5683 emerged as a potential prognostic biomarker, showing a favorable correlation with RFS and suppressing tumorigenicity under 2D and 3D conditions in triple-negative breast cancer (TNBC) models. Findings were further extended to the MCF7 hormone receptor positive (HR+) model. Transcriptomic profiling of hsa-miR-5683 overexpressing TNBC cells revealed its potential role in key oncogenic pathways. Integration of downregulated genes and CRISPR-Cas9 perturbational effects identified ACLY, RACGAP1, AK4, MRPL51, CYB5B, MKRN1, TMEM230, NUP54, ANAPC13, PGAM1, and SOD1 as bona fide gene targets for hsa-miR-5683.</p><p><strong>Conclusions: </strong>Our data provides comprehensive miRNA expression atlas in breast cancer subtypes and underscores the prognostic and therapeutic significance of numerous miRNAs, including hsa-miR-5683 in TNBC. The identified gene targets unravel the intricate regulatory network in TNBC progression, suggesting promising avenues for further research and targeted therapeutic interventions.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"377"},"PeriodicalIF":5.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615319","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":"Olaparib enhancing radiosensitization and anti-metastatic effect of oral cancer by targeting IL-17A signal.","authors":"Chih-Chia Yu, Hon-Yi Lin, Michael W Y Chan, Shu-Fen Wu, Wen-Yen Chiou, Moon-Sing Lee, Chen-Lin Chi, Ru-Inn Lin, Feng-Chun Hsu, Hsuan-Ju Yang, Liang-Cheng Chen, Chia-Hui Chew, Shih-Kai Hung","doi":"10.1186/s12935-024-03547-3","DOIUrl":"10.1186/s12935-024-03547-3","url":null,"abstract":"<p><strong>Purpose: </strong>We tested whether the PARP inhibitor, Olaparib, can effectively enhance radiosensitivity while inhibiting OSCC growth and metastasis in vitro and in vivo. Patient samples were used for survival validation.</p><p><strong>Methods: </strong>The present study investigated the effect of Olaparib and ionizing radiation (IR) on clonogenic, migratory, and invasive ability in human IR-sensitive (OML1) and IR-resistant (OML1-R) OSCC cell lines. We next explored the underlying mechanism with ELISA and a Western blotting assay. Two in vivo mouse models were established to investigate the efficacy of Olaparib combined with radiotherapy (RT) on local tumor growth and lung metastasis. IL-17 A expression was confirmed in tissue specimens of OSCC patients by immunohistochemistry.</p><p><strong>Results: </strong>We found that Olaparib, in combination with IR, substantially inhibited cell growth, migration, and invasion in vitro. Mechanistically, the Olaparib treatment significantly reduced the secretion of IL-17 A in irradiated OSCC cells by attenuating NF-κB and p38 activity. Consistently, Olaparib enhanced the radiosensitivity and, with RT, synergistically reduced both tumor growth and lung metastasis in mice. In addition, OSCC patients with high IL-17 A expression were substantially associated with an increased risk of lymph node involvement and worse survival.</p><p><strong>Conclusions: </strong>This study has highlighted that Olaparib displays radiosensitizing and antimetastatic effects by inhibiting the IL-17 A-dependent signal. Remarkably, Olaparib could provide a remarkable anticancer efficacy to improve treatment response in OSCC patients with recurrent/metastatic disease after RT.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"373"},"PeriodicalIF":5.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615321","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":"E3 ubiquitin ligase HECW2: a promising target for tumour therapy.","authors":"Hui Shen, Qianrui Kou, Linxin Shao, Jing Zhang, Fang Li","doi":"10.1186/s12935-024-03563-3","DOIUrl":"10.1186/s12935-024-03563-3","url":null,"abstract":"<p><p>Ubiquitination is a prevalent post-translational modification that plays a crucial role in a wide range of pathophysiological processes, including cell proliferation, apoptosis, autophagy, immune response, and DNA damage repair. Among the enzymes involved in ubiquitination, E3 ubiquitin ligases are particularly significant, serving as key regulators of numerous diseases, including tumours. This review focuses on HECW2 (HECT, C2, and WW domain-containing E3 ubiquitin protein ligase 2, also known as NEDL2), providing a comprehensive overview of its interactors and its pathological roles in tumorous cancer and other diseases. The insights gained from this review may contribute to the development of novel treatment strategies for various diseases, particularly tumours.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"374"},"PeriodicalIF":5.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615306","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 Note: ZKSCAN3 drives tumor metastasis via integrin β4/FAK/AKT mediated epithelial-mesenchymal transition in hepatocellular carcinoma.","authors":"Jieqiong Li, Nan Hao, Juan Han, Mi Zhang, Xiaomei Li, Nan Yang","doi":"10.1186/s12935-024-03566-0","DOIUrl":"10.1186/s12935-024-03566-0","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"375"},"PeriodicalIF":5.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635892","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":"High CTLA-4 gene expression is an independent good prognosis factor in breast cancer patients, especially in the HER2-enriched subtype.","authors":"Yoel G Montoyo-Pujol, José J Ponce, Silvia Delgado-García, Tina A Martín, Hortensia Ballester, Elena Castellón-Molla, Angela Ramos-Montoya, Inmaculada Lozano-Cubo, J Miguel Sempere-Ortells, Gloria Peiró","doi":"10.1186/s12935-024-03554-4","DOIUrl":"10.1186/s12935-024-03554-4","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-related death worldwide. This heterogeneous disease has been historically considered a non-immunogenic type of cancer. However, recent advances in immunotherapy have increased the interest in knowing the role of the immune checkpoints (IC) and other immune regulation pathways in this neoplasia.</p><p><strong>Methods: </strong>In this retrospective study, we evaluated the correlation of mRNA expression of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FOXO1 with clinicopathological factors and BC patient's outcome by real-time quantitative polymerase chain reaction (qPCR).</p><p><strong>Results: </strong>Our results showed that immunoregulatory gene expression depends on BC immunophenotype being CTLA-4 and PDCD1 (PD1) overexpressed on triple-negative/basal-like (TN/BL) and luminal B/HER2-positive phenotypes, respectively, and CD276 (B7-H3), JAK2 and FOXO1 associated with both luminal A and luminal B/HER2-negative tumors. In addition, we found that these genes can also be related to aggressive and non-aggressive clinicopathological characteristics in BC. Finally, survival analysis showed that CTLA-4 expression levels emerge as a significant independent factor of good prognosis in BC patients, especially in the HER2-enriched subtype.</p><p><strong>Conclusion: </strong>Considering all these data, we can conclude that the expression of immunoregulatory genes depends on tumor phenotype and has potential clinical implications in BC patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"371"},"PeriodicalIF":5.3,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615317","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":"Correction to: SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas.","authors":"Peng Wang, Jingjing Zhang, Shuai He, Boan Xiao, Xiaobin Peng","doi":"10.1186/s12935-024-03556-2","DOIUrl":"10.1186/s12935-024-03556-2","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"372"},"PeriodicalIF":5.3,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615305","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 Note: LncRNA LINC00261 overexpression suppresses the growth and metastasis of lung cancer via regulating miR-1269a/FOXO1 axis.","authors":"Caixia Guo, Hongmei Shi, Yuli Shang, Yafei Zhang, Jiajia Cui, Hongtao Yu","doi":"10.1186/s12935-024-03565-1","DOIUrl":"10.1186/s12935-024-03565-1","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"370"},"PeriodicalIF":5.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635890","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":"Comprehensive review of LncRNA-mediated therapeutic resistance in non-small cell lung cancer.","authors":"Xin Ge, Zichu Shen, Yuxin Yin","doi":"10.1186/s12935-024-03549-1","DOIUrl":"10.1186/s12935-024-03549-1","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of gene expression through diverse mechanisms, including regulation of protein localization, sequestration of miRNAs, recruitment of chromatin modifiers, and modulation of signaling pathways. Accumulating evidence highlights their pivotal roles in tumor initiation, progression, and the development of therapeutic resistance. In this review, we comprehensively summarized the existing literature to identify lncRNAs associated with treatment responses in non-small cell lung cancer (NSCLC). Specifically, we categorized these lncRNAs based on their mechanisms of action in mediating resistance to chemotherapy, targeted therapy, and radiotherapy. Our analysis revealed that aberrant expression of various lncRNAs contributes to the development, metastasis, and therapeutic resistance in NSCLC, ultimately leading to poor clinical outcomes. By elucidating the intricate mechanisms through which lncRNAs modulate therapeutic responses, this review aims to provide mechanistic insights into the heterogeneous treatment outcomes observed in NSCLC patients and unveil potential therapeutic targets for overcoming drug resistance.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"369"},"PeriodicalIF":5.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615301","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":"Machine learning unveils key Redox signatures for enhanced breast Cancer therapy.","authors":"Tao Wang, Shu Wang, Zhuolin Li, Jie Xie, Kuiying Du, Jing Hou","doi":"10.1186/s12935-024-03534-8","DOIUrl":"10.1186/s12935-024-03534-8","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer remains a leading cause of mortality among women worldwide, necessitating innovative prognostic models to enhance treatment strategies.</p><p><strong>Methods: </strong>Our study retrospectively enrolled 9,439 breast cancer patients from 12 independent datasets and single-cell data from 12 patients (64,308 cells). Moverover, 30 in-house clinical cohort were collected for validation. We employed a comprehensive approach by combining ten distinct machine learning algorithms across 108 different combinations to scrutinize 88 pre-existing signatures of breast cancer. To affirm the efficacy of our developed model, immunohistochemistry assays were performed. Additionally, we investigated various potential immunotherapeutic and chemotherapeutic interventions.</p><p><strong>Results: </strong>This study introduces an Artificial Intelligence-aided Redox Signature (AIARS) as a novel prognostic tool, leveraging machine learning to identify critical redox-related gene signatures in breast cancer. Our results demonstrate that AIARS significantly outperforms existing prognostic models in predicting breast cancer outcomes, offering a robust tool for personalized treatment planning. Validation through immunohistochemistry assays on samples from 30 patients corroborated our results, underscoring the model's applicability on a wider scale. Furthermore, the analysis revealed that patients with low AIARS expression levels are more responsive to immunotherapy. Conversely, those exhibiting high AIARS were found to be more susceptible to certain chemotherapeutic agents, including vincristine.</p><p><strong>Conclusions: </strong>Our study underscores the importance of redox biology in breast cancer prognosis and introduces a powerful machine learning-based tool, the AIARS, for personalized treatment strategies. By providing a more nuanced understanding of the redox landscape in breast cancer, the AIARS paves the way for the development of redox-targeted therapies, promising to enhance patient outcomes significantly. Future work will focus on clinical validation and exploring the mechanistic roles of identified genes in cancer biology.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"368"},"PeriodicalIF":5.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615318","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 Note: LINC00115 promotes stemness and inhibits apoptosis of ovarian cancer stem cells by upregulating SOX9 and inhibiting the Wnt/β-catenin pathway through competitively binding to microRNA-30a.","authors":"Rui Hou, Luo Jiang","doi":"10.1186/s12935-024-03561-5","DOIUrl":"10.1186/s12935-024-03561-5","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"367"},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635889","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}