Cancer Cell International最新文献

{"title":"YEATS2: a novel cancer epigenetic reader and potential therapeutic target.","authors":"Kangkang Ji, Guoping Chen, Yan Wang, Yunyi Li, Jian Chen, Mingqian Feng","doi":"10.1186/s12935-025-03797-9","DOIUrl":"https://doi.org/10.1186/s12935-025-03797-9","url":null,"abstract":"<p><p>YEATS2, an evolutionarily conserved reader of histone acylation marks (H3K27ac, H3K27cr, H3K27bz), functions as a central oncogenic driver in diverse cancers, including non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC). Its structurally plastic YEATS domain bridges acyl-CoA metabolism to chromatin remodeling, amplifying transcription of survival genes such as MYC, BCL2, and PD-L1. YEATS2 orchestrates malignancy-specific programs-sustaining ribosome biogenesis in NSCLC through ATAC complex recruitment, enhancing NF-κB-dependent immune evasion in PDAC, and activating PI3K/AKT-driven metabolic rewiring in HCC. Structural studies demonstrate a unique aromatic cage architecture that selectively engages diverse acylated histones. Although pyrazolopyridine-based inhibitors targeting the YEATS domain show preclinical efficacy, developing isoform-selective agents remains challenging. Clinically, YEATS2 overexpression correlates with therapy resistance and may synergize with immune checkpoint blockade. This review integrates mechanistic insights into the role of YEATS2 in epigenetic regulation, evaluates its therapeutic potential, and proposes future directions: elucidating full-length complex topologies, mapping synthetic lethal interactors, and optimizing selective inhibitors. Disrupting YEATS2-mediated epigenetic adaptation presents novel opportunities for precision cancer therapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"162"},"PeriodicalIF":5.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982730","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":"Liquid biopsy-derived extracellular vesicle protein biomarkers for diagnosis and prognostic assessment of lung squamous cell carcinoma.","authors":"Sheng Ma, Na Zhao, Xin Dong, Yaru Wang, Lei Song, Ruiqi Zheng, Xiaochen Zhi, Congcong Ma, Shujun Cheng, Jie Li, Yutao Liu, Ting Xiao","doi":"10.1186/s12935-025-03792-0","DOIUrl":"https://doi.org/10.1186/s12935-025-03792-0","url":null,"abstract":"<p><strong>Background: </strong>For patients with nodules detected in imaging that are indeterminate for malignancy, achieving accurate, early, and non-invasive diagnosis of Lung Squamous Cell Carcinoma (LUSC) remains a significant challenge. Therefore, we aimed to establish diagnostic and prognostic models by identifying plasma extracellular vesicles (EVs) associated protein biomarkers specific to LUSC.</p><p><strong>Methods: </strong>This study employed a novel nanomaterial, NaY, for the enrichment of EVs from plasma. Validation was conducted through transmission electron microscopy, nanoparticle tracking analyses, and Western blotting. Machine learning algorithms were utilized to compute protein biomarkers associated with LUSC and establish a diagnostic model. Additionally, a prognostic prediction model for LUSC was developed using a combination of 101 machine learning algorithms. Risk scoring of patients was performed to explore the underlying reasons for prognostic differences between high and low-risk groups.</p><p><strong>Results: </strong>The results of three experiments demonstrate that the new nanomaterial NaY effectively enriches EVs from plasma. Analysis of the enriched profile reveals pathways related to glycolysis/gluconeogenesis and carbon metabolism enriched in plasma EVs of LUSC patients. Thirty-eight LSCC-related EV biomarkers were identified, from which five proteins (TUBB3, RPS7, RPLP1, KRT2, and VTN) were selected to establish a diagnostic model distinguishing between benign and LUSC nodules. The diagnostic efficacy of RPS7 and VTN was further validated in independent samples using ELISA experiments. Furthermore, DPYD, GALK1, CDC23, UBE2L3, RHEB, and PSME1 were determined as potential prognostic biomarkers. Subsequently, risk scores were computed for each sample, classifying all patients into high and low-risk groups. Enrichment analysis revealed that EVs from the high-risk group contained proteins promoting cell proliferation and invasion, while those from the low-risk group were enriched in immune-related protein biomarkers.</p><p><strong>Conclusions: </strong>The novel nanomaterial NaY effectively enriches EVs from plasma. Utilizing plasma EV biomarkers, the diagnostic model demonstrates strong discriminative ability between benign and malignant pulmonary nodules in patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"161"},"PeriodicalIF":5.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977025","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":"Identifying PSIP1 as a critical R-loop regulator in osteosarcoma via machine-learning and multi-omics analysis.","authors":"Jiangbo Nie, Shijiang Wang, Yanxin Zhong, Feng Yang, Jiaming Liu, Zhili Liu","doi":"10.1186/s12935-025-03775-1","DOIUrl":"https://doi.org/10.1186/s12935-025-03775-1","url":null,"abstract":"<p><p>Dysregulation of R-loops has been implicated in tumor development, progression, and the regulation of tumor immune microenvironment (TME). However, their roles in osteosarcoma (OS) remain underexplored. In this study, we firstly constructed a novel R-loop Gene Prognostic Score Model (RGPSM) based on the RNA-sequencing (RNA-seq) datasets and evaluated the relationships between the RGPSM scores and the TME. Additionally, we identified key R-loop-related genes involved in OS progression using single-cell RNA sequencing (scRNA-seq) dataset, and validated these findings through experiments. We found that patients with high-RGPSM scores exhibited poorer prognosis, lower Huvos grades and a more suppressive TME. Moreover, the proportion of malignant cells was significantly higher in the high-RGPSM group. And integrated analysis of RNA-seq and scRNA-seq datasets revealed that PC4 and SRSF1 Interacting Protein 1 (PSIP1) was highly expressed in osteoblastic and proliferative OS cells. Notably, high expression of PSIP1 was associated with poor prognosis of OS patients. Subsequent experiments demonstrated that knockdown of PSIP1 inhibited OS progression both in vivo and in vitro, leading increased R-loop accumulation and DNA damage. Conversely, overexpression of PSIP1 facilitated R-loop resolution and reduced DNA damage induced by cisplatin. In conclusion, we developed a novel RGPSM that effectively predicted the outcomes of OS patients across diverse cohorts and identified PSIP1 as a critical modulator of OS progression by regulating R-loop accumulation and DNA damage.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"159"},"PeriodicalIF":5.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959265","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":"Taurochenodeoxycholic acid suppresses the progression of glioblastoma via HMGCS1/HMGCR/GPX4 signaling pathway in vitro and in vivo.","authors":"Xiumin Xue, Ziwan He, Furui Liu, Qian Wang, Zhichao Chen, Lin Lin, Danni Chen, Yinfeng Yuan, Zhihui Huang, Yongjie Wang","doi":"10.1186/s12935-025-03782-2","DOIUrl":"https://doi.org/10.1186/s12935-025-03782-2","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is the foremost prevalent and highly aggressive intracranial malignancy, which urgently needs safer and more efficacious therapeutic strategies. Our research aimed to investigate the impact and the underlying mechanism of Taurochenodeoxycholic acid (TCDCA) on GBM. In this study, we explored the suppressive effect of TCDCA in vitro by qualification of proliferation and migration assays and flow cytometry, and subsequently predicted the potential anti-GBM mechanism of TCDCA by mRNA sequencing and the following rescue experiments. An orthotopic GBM model in C57BL/6 mice further demonstrated the anti-GBM mechanism of TCDCA. In vitro experiments verified that TCDCA inhibited the growth and migration of GBM cells and induced cell cycle arrest at the G2/M phase. Subsequent mechanism investigations showed that upregulation of HMGCS1 and HMGCR and downregulation of glutathione peroxidase-4 (GPX4) was observed in GBM cells by TCDCA treatment. Notably, inhibitory effects of proliferation and migration as well as induction of ferroptosis by TCDCA were partially restored by Simvastatin (SIN), a competitive HMGCR inhibitor. Furthermore, TCDCA showed an anti-GBM effect in an orthotopic transplantation model in vivo. TCDCA impedes GBM progression by virtue of this intricately orchestrated molecular cascade, through HMGCS1/HMGCR/GPX4 signaling axis, thus unveiling a novel therapeutic avenue warranting further scrutiny in the treatment landscape of GBM.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"160"},"PeriodicalIF":5.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981225","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":"Integrating multi-cohort machine learning and clinical sample validation to explore peripheral blood mRNA diagnostic biomarkers for prostate cancer.","authors":"Xingyu Zhong, Yuxuan Yang, Haodong He, Yifan Xiong, Mingliang Zhong, Shaogang Wang, Qidong Xia","doi":"10.1186/s12935-025-03788-w","DOIUrl":"https://doi.org/10.1186/s12935-025-03788-w","url":null,"abstract":"<p><strong>Background: </strong>The global incidence of prostate cancer (PCa) has been rising annually, and early diagnosis and treatment remain pivotal for improving therapeutic outcomes and patient prognosis. Concurrently, advancements in liquid biopsy technology have facilitated disease diagnosis and monitoring, with its minimally invasive nature and low heterogeneity positioning it as a promising approach for predicting disease progression. However, current liquid biopsy strategies for PCa predominantly rely on prostate-specific antigen (PSA), which lacks specificity and compromises diagnostic accuracy. Thus, there is an urgent need to identify novel liquid biopsy biomarkers to enable early and precise PCa diagnosis.</p><p><strong>Methods: </strong>We integrated 12 machine learning algorithms to construct 113 combinatorial models, screening and validating an optimal PCa diagnostic panel across five datasets from TCGA and GEO databases. Subsequently, the biological feasibility of the selected predictive model was verified in one prostate epithelial cell line and five PCa cell lines. Robust RNA diagnostic targets were further validated for their expression in plasma samples to establish an RNA-based liquid biopsy strategy for PCa. Finally, plasma samples from PCa and benign prostatic hyperplasia (BPH) patients at Wuhan Tongji Hospital were collected to evaluate the strategy's clinical significance.</p><p><strong>Results: </strong>Differential analysis identified 1,071 candidate mRNAs, which were input into the integrated machine learning framework. Among the 113 combinatorial models, the 9-gene diagnostic panel selected by the Stepglm[both] and Enet[alpha = 0.4] algorithms demonstrated the highest diagnostic efficacy (mean AUC = 0.91), including JPH4, RASL12, AOX1, SLC18A2, PDZRN4, P2RY2, B3GNT8, KCNQ5, and APOBEC3C. Cell line experiments further validated AOX1 and B3GNT8 as robust RNA biomarkers, both exhibiting consistent PCa-specific expression in human plasma samples. In liquid biopsy analyses, AOX1 and B3GNT8 outperformed PSA in diagnostic accuracy, achieving a combined AUC of 0.91. Notably, these biomarkers also demonstrated diagnostic utility in patients with ISUP ≤ 2.</p><p><strong>Conclusions: </strong>Through an integrated machine learning approach and clinical validation, we developed an RNA-based diagnostic panel for PCa. Specifically, we identified AOX1 and B3GNT8 as novel liquid biopsy biomarkers with promising clinical diagnostic value. These findings provide new targets and insights for early and precise PCa diagnosis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"158"},"PeriodicalIF":5.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976319","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":"Hsa_circ_0072088 promotes non-small cell lung cancer progression through modulating miR-1270/TOP2A axis.","authors":"Sixuan Li, Zhigang Cui, Min Gao, Yanan Shan, Yihong Ren, Yuxin Zhao, Di Wang, Tingyu Meng, Hongxu Liu, Zhihua Yin","doi":"10.1186/s12935-025-03749-3","DOIUrl":"https://doi.org/10.1186/s12935-025-03749-3","url":null,"abstract":"<p><p>According to the data released by the International Agency for Research on Cancer (IARC) in 2020, lung cancer ranks second among newly diagnosed malignant tumors globally. As a special class of non-coding RNA, circRNA has become a new hotspot in the field of biomarker research. With the continuous deepening of molecular-level investigations, the underlying mechanisms of circRNA are being gradually unveiled. The more widely studied mechanism is the competitive endogenous RNA mechanism of circRNA. Studies related to circRNA expression were searched in GEO database and statistically analyzed using the \"limma\" package and weighted gene co-expression network analysis. The expression of circRNA, microRNA and mRNA in cells and tissues were examined via qRT-PCR. MTS assay was used to measure cell proliferation, Transwell assay was used to measure cell migration, and apoptosis assay was carried out to detect cell apoptosis. Additionally, a dual-luciferase reporter assay was further executed to explore the targeted binding relationships between circRNA-microRNA and microRNA-mRNA. It was discovered that hsa_circRNA_103809 was differentially highly expressed in non-small cell lung cancer cells, whereas miR-1270 was differentially lowly expressed. The knockdown of circ_0072088 inhibited the cell proliferation and migration, while promoting cell apoptosis. The same biological function was found with the overexpression of miR-1270. The rescue experiment further validated that circ_0072088 could regulate the biological function of cells by influencing miR-1270. Finally, the targeted binding relationship was verified by dual luciferase reporting experiment. In conclusion, circ_0072088 is differentially highly expressed in non-small cell lung cancer and can affect the progression of non-small cell lung cancer through the circ_0072088/miR-1270/TOP2A axis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"156"},"PeriodicalIF":5.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966188","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":"Single-cell RNA sequencing reveals cellular and molecular heterogeneity in extensive-stage small cell lung cancer with different chemotherapy responses.","authors":"Zhan Gu, Yongqing Heng, Rui Fan, Jie Luo, Lixia Ju","doi":"10.1186/s12935-025-03785-z","DOIUrl":"https://doi.org/10.1186/s12935-025-03785-z","url":null,"abstract":"<p><p>Despite its rapid growth and early metastasis, small cell lung cancer (SCLC) is more chemosensitive than other lung cancers. However, some patients with extensive-stage SCLC (ES-SCLC) do not respond to first-line chemotherapy, resulting in poorer prognoses due to inter- and intratumoral heterogeneity. In this study, we conducted single-cell RNA sequencing of 9 treatment-naive ES-SCLC samples. Based on comprehensive imaging evidence collected before and after two cycles of first-line chemotherapy and sample types, the 9 samples were categorized into three groups: progressive disease with the pleural effusion sample (PD_PE group, n = 1), progressive disease with the primary tumor samples (PD_TU group, n = 2), and partial response with the primary tumor samples (PR_TU group, n = 6). Based on transcriptomic landscape and cell type composition, the PD samples represent a multicellular ecosystem distinct from PR samples. The immune response, along with the elevated expression of immune-related genes such as LTF, SLPI, SPARC and IGLV1-51, might correlate with a poor first-line chemotherapy response in ES-SCLC. We also observed that T cells, particularly effector T cells, were more abundant in PD_TU group, with TNFA signaling via NFκB being significantly enriched. The PD_TU group was strongly enriched with macrophages and tumor-associated macrophages (TAMs), and angiogenesis in TAMs was highly enriched. Immunomodulatory fibroblasts were highly abundant in PD_TU group, and the pathways of epithelial-mesenchymal transition and angiogenesis were upregulated. This study offers the first comprehensive insights into the cellular and molecular heterogeneity in treatment-naive patients with ES-SCLC with different chemotherapy responses.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"157"},"PeriodicalIF":5.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980519","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":"Identification and exploration of key genes associated with radioresistance in lung adenocarcinoma.","authors":"Ying Wang, Yangyang Shang, Mingyu Hua, Yidi Wang, Beina Hui, Weibin Hu, Mengke Zhu, Xiaozhi Zhang, Jing Li","doi":"10.1186/s12935-025-03783-1","DOIUrl":"https://doi.org/10.1186/s12935-025-03783-1","url":null,"abstract":"<p><strong>Background: </strong>Radiation resistance in lung adenocarcinoma (LUAD) remains a primary obstacle limiting radiotherapy efficacy. However, the detailed factors and molecular mechanisms influencing LUAD radiosensitivity are not fully understood.</p><p><strong>Methods: </strong>Radioresistance-related genes (RRRGs) were screened by RNA sequencing and bioinformatics analysis, and a prediction model for radiotherapy efficacy was developed via LASSO-Cox regression analysis. We specifically focused on Stanniocalcin 2 (STC2) due to its prognostic significance and validated its expression through immunohistochemical staining (IHC) in pathological samples from LUAD patients. A STC2 knockdown (siSTC2) A549 cell line was created, and Western blotting, CCK8, and colony formation assays were performed to investigate STC2's involvement in radioresistance.</p><p><strong>Results: </strong>An efficacy prediction model was constructed using 6 RRRGs (FCGBP, SLCO4A1, ALDH3A1, STC2, TERT, CYP24A1). IHC analysis of 74 LUAD patients showed significantly higher STC2 expression in radiotherapy non-responders (N-Res) versus responders (Res) (p < 0.05). Patients with elevated STC2 levels experienced shorter overall survival (OS). Western blotting revealed higher STC2 expression in irradiated (IR) A549 cells compared to non-irradiated (N-IR) (p < 0.05). CCK8 assays results suggested that knockdown of STC2 resulted in a significant reduction in cell proliferation ability (p < 0.05), and colony formation assays confirmed a significant decrease in clonogenic ability of siSTC2 cells compared to controls (p < 0.05).</p><p><strong>Conclusion: </strong>STC2 plays a significant role in mediating LUAD cell radioresistance, with high expression correlating with poor prognosis. Therefore, STC2 represents a promising therapeutic target for overcoming LUAD radioresistance.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"155"},"PeriodicalIF":5.3,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966847","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":"To be or not to be: navigating the influence of MicroRNAs on cervical cancer cell death.","authors":"Mohammad Taghizadieh, Masoumeh Kalantari, Roksana Bakhshali, Sepehr Kobravi, Shayan Khalilollah, Hossein Bannazadeh Baghi, Mobina Bayat, Javid Sadri Nahand, Reza Akhavan-Sigari","doi":"10.1186/s12935-025-03786-y","DOIUrl":"https://doi.org/10.1186/s12935-025-03786-y","url":null,"abstract":"<p><p>With all diagnostic and therapeutic advances, such as surgery, radiation- and chemo-therapy, cervical cancer (CC) is still ranked fourth among the most frequent cancers in women globally. New biomarkers and therapeutic targets are warranted to be discovered for the early detection, treatment, and prognosis of CC. As component of the non-coding RNA's family, microRNAs (miRNAs) participate in several cellular functions such as cell proliferation, gene expression, many signaling cascades, apoptosis, angiogenesis, etc. MiRNAs can suppress or induce programmed cell death (PCD) pathways by altering their regulatory genes. Besides, abnormal expression of miRNAs weakens or promotes various signaling pathways associated with PCD, resulting in the development of human diseases such as CC. For that reason, understanding the effects that miRNAs exert on the various modes of tumor PCD, and evaluating the potential of miRNAs to serve as targets for induction of cell death and reappearance of chemotherapy. The current study aims to define the effect that miRNAs exert on cell apoptosis, autophagy, pyroptosis, ferroptosis, and anoikis in cervical cancer to investigate possible targets for cervical cancer therapy. Manipulating the PCD pathways by miRNAs could be considered a primary therapeutic strategy for cervical cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"153"},"PeriodicalIF":5.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984349","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":"Molecular and phenotypic characterization of 5-FU resistant colorectal cancer cells: toward enrichment of cancer stem cells.","authors":"Amirhesam Babajnai, Saeed Rahmani, Mohammad Jamal Asadi, Elmira Gheytanchi, Glavizh Adibhesami, Faezeh Vakhshiteh, Zahra Madjd","doi":"10.1186/s12935-025-03758-2","DOIUrl":"https://doi.org/10.1186/s12935-025-03758-2","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) as a subgroup of cells within a tumor capable of self-renewal, thereby driving tumor initiation and spread. Addressing treatment failures in cancer, linked to CSCs and their resistance mechanisms, requires effective preclinical models for testing targeted therapies. Caco2- and HT-29-resistant cells were generated by repeated treatment of cells with growing concentrations of 5-fluorouracil (5-FU) anticancer drug for an extended time. The sensitivity of 5-FU-resistant cells was evaluated by cytotoxicity assay. Stemness, epithelial-mesenchymal transition (EMT), migration and drug resistance characteristics were assessed through gene expression investigation by real-time PCR. The expression of CD44, CD133, and CD66 were evaluated by flow cytometry. To end, the bioinformatic analysis estimated the molecular function and biological pathways considering the differential expression of selected genes and proteins. 5-FU-exposed cells displayed increased resistance to 5-FU. The gene expression analysis showed an upregulation of stemness genes (KLF4, SOX2, OCT4, C-MYC), enhanced scavenging system, and elevated expression of CSC surface markers (CD44 and CD133) compared to parental cells. Additionally, pro-EMT genes (TWIST1, SNAIL1, ZEB1, Vimentin, and N-cadherin) were significantly upregulated compared to parental cells, with the downregulation of E-cadherin as an EMT suppressor gene reflected in increased migration capacity. Moreover, increased expression of ABC transporter genes (ABCB1, ABCC1) was observed, correlating with enhanced drug resistance. The bioinformatic analysis highlighted pathways related to microRNAs in cancer, cells pluripotency, and proteoglycans. Methods of drug exposure take priority over spheroid formation, particularly due to their enhanced efficacy in stemness, EMT, and surface markers. This positions them as a promising protocol for establishing experimental models of CSCs.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"154"},"PeriodicalIF":5.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974890","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}