Analytical Cellular Pathology最新文献

{"title":"Comparison and Analysis of the Drug-Resistance Mechanism of Osimertinib- and Almonertinib-Resistant Cell Lines.","authors":"Chuangjie Zheng, Yingfang Ren, Ke Wang, Xinrong Chen, Jiahao Tao, Cuifen Zhang, Zeyu Liu, Lingling Sun, Linzhu Zhai","doi":"10.1155/ancp/5578693","DOIUrl":"https://doi.org/10.1155/ancp/5578693","url":null,"abstract":"<p><p><b>Background:</b> Non-small-cell lung cancer remains the leading cause of cancer-related deaths globally, and epidermal growth factor receptor mutations have been identified as crucial drivers of the disease. Encouragingly, epidermal growth factor receptor tyrosine kinase inhibitors have demonstrated promising clinical outcomes. Nonetheless, the emergence of resistance to third-generation EGFR-TKIs like osimertinib and almonertinib is an inevitable challenge. <b>Methods:</b> In this study, we generated almonertinib-resistant cell lines from H-1975 and HCC827 lung cancer cell lines. We utilized various assays, including cell proliferation assays, hematoxylin and eosin staining, and cell cycle assays, to investigate the characteristics of drug-resistant cells. Additionally, we performed RNA transcriptome sequencing to identify differentially expressed genes (DEGs) in almonertinib-resistant cells. To further expand our analysis, we obtained sequencing data of osimertinib-resistant cells from the Gene Expression Omnibus (GEO) dataset and identified DEGs in these cells. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to assess the biological functions and signaling mechanisms associated with DEGs. Furthermore, the survival prognosis and immune cell infiltration of common differentially expressed genes (co-DEGs) in osimertinib-and almonertinib-resistant cells were analyzed, and the expression of a co-DEG (<i>IGFBP7</i>) was verified through quantitative reverse transcriptase polymerase chain reaction (qPCR) and western blotting (WB) assays. Gene knockdown plasmids were constructed for cell transfection, and the invasive ability of resistant cells was assessed using a Transwell assay following the knockdown of <i>IGFBP7</i>. <b>Results:</b> Experimental cell counting kit-8 cytotoxicity studies revealed intriguing findings regarding drug resistance in lung cancer cells. Specifically, the IC<sub>50</sub> values and resistance factors of H-1975 and HCC827 cells were found to be 1.9 nM and 833.58 and 2.2 nM and 631.95, respectively. In addition to these quantitative results, comparative observations of the cell morphology and cell cycle revealed significant alterations in drug-resistant cells. Transcriptome sequencing analysis identified 220 DEGs between H-1975 and H-1975/AR and 736 DEGs between HCC827 and HCC827/AR. Interestingly, screening of overlapping DEGs with osimertinib-resistant cells in the GEO database identified some common genes, such as <i>IGFBP7</i> and <i>RFTN1</i>, which were found to be associated with the improved prognosis of non-small-cell lung cancer by survival analysis. Furthermore, GO analysis and KEGG pathway enrichment analysis revealed different pathway changes in different drug-resistant cells. Survival analysis indicated that a higher expression of co-DEGs (<i>IGFBP7</i>, <i>RFTN1</i>) was associated with a more favorable prognosis. Furthermore, <i>IGFBP7</i> expression is stro","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"5578693"},"PeriodicalIF":2.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11991788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding Osteosarcoma's Lactylation Gene Expression: Insights Into Prognosis, Immune Dynamics, and Treatment.","authors":"Cheng Peng, Chaoqun You, Shuang Cao, Linfei Cheng, Jiaji Ren, Jiashi Cao, Jing Wang, Tielong Liu","doi":"10.1155/ancp/6517238","DOIUrl":"10.1155/ancp/6517238","url":null,"abstract":"<p><p>Osteosarcoma (OS), characterized by a complex tumor microenvironment, poses challenges in treatment, metastasis, and therapy resistance. This study examined the impact of lactylation, a posttranslational modification, on gene expression and tumor behavior in OS, particularly its influence on prognosis, immune cell infiltration, and chemotherapy response. Utilizing data from the Gene Expression Omnibus series accession number 21257 (GSE21257) and the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) datasets, the investigation focused on analyzing the expression profiles of 267 lactylation modifier genes, which were selected from a total of 336 lactylation-related genes compiled from various studies in the literature. The methods included unsupervised clustering using \"ConsensusClusterPlus\" heatmap generation with \"pheatmap\" pathway analysis from several databases, and immune cell infiltration assessment using the \"single-sample Gene Set Enrichment Analysis (ssGSEA)\" function. The research revealed 36 significant lactylation-related genes in OS, categorizing them into two clusters with distinct survival and biological characteristics. One cluster demonstrated poor prognosis due to increased tumor cell proliferation and specific immune cell variations, also showcasing genes that enhance tumor growth and metastasis, thus indicating its aggressive nature and adverse outcomes for patients. These insights are crucial for understanding the molecular mechanisms of OS and identifying therapeutic targets. Therefore, the study elucidates the role of lactylation-related genes in the prognosis, pathogenesis, and treatment response of OS, laying the groundwork for further exploration into potential therapeutic targets and the underlying mechanisms within OS.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"6517238"},"PeriodicalIF":2.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association of <i>VDR/FokI</i> Gene Polymorphism and Protein Expression With Histopathological Alterations in Patients With Thyroid Colloid Nodule.","authors":"Mariwan F Abdalfatah, Abdullah A Shareef, Lana S Saleh, Mustafa F Rajab, Shukur W Smail, Saman S Abdulla, Harem Khdir Awla, Rivan H Ishaac, Kazhal S Ibrahim, Mazyar J Ahmed, Fairuz A Kakasur, Khder Hussein Rasul","doi":"10.1155/ancp/6796922","DOIUrl":"10.1155/ancp/6796922","url":null,"abstract":"<p><p><b>Objective:</b> Colloid nodules are common and benign thyroid lesions that usually progress slowly and are asymptomatic. It requires follow-up because untreated colloid nodules may develop into malignant tumor. The study aimed to examine the contributions of vitamin D receptor (VDR) expression, VDR/FokI (rs2228570) genotypes, and serum vitamin D level to the susceptibility to colloid nodules. <b>Methods:</b> One hundred forty subjects (80 patients and 60 controls) were enrolled and VDR FokI was determined by PCR in formalin fixed paraffin embedded (FFPE) blocks of the patients and blood of controls. Moreover, VDR protein expression was evaluated by immunohistochemistry using specific VDR monoclonal antibody in the tissue sections of patients and serum vitamin D were measured simultaneously using enzyme-linked immunosorbent assay (ELISA). <b>Results:</b> Sixty-two (77.5%) cases showed strong immunoreactivity score (IRS) of cytoplasmic staining. Strong IRS were significantly observed in samples with larger nodule size (<i>p</i> value: 0.0094), multinodules (<i>p</i> value: 0.0054), and carriers of CC genotypes (<i>p</i> value: 0.0034). TT homozygous genotype revealed significantly (<i>p</i> value: 0.029 and odds ratio (OR): 0.11) protective factor for colloid nodules. In addition, nodule size was significantly (<i>p</i> value: 0.016) larger among CC carriers. Moreover, vitamin D level and category were nonsignificantly difference between patients and controls. <b>Conclusion:</b> Our results reveal prominent cytoplasmic VDR expression, suggesting a distinct distribution pattern and offering valuable insights into its potential role in colloid nodules. VDR expression increases with increasing size and number of nodules. Regarding FokI genotypes, TT genotype was less likely to develop colloid nodule. These findings contribute to our understanding of cellular characteristics of this condition and may have implications for future research and clinical management.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"6796922"},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA Circ_0079226 Plays an Oncogenic Role in Gastric Cancer via the miR-155-5p/FOXK1/AKT Pathway.","authors":"Hui Zhang, Zhisheng Huang, Yingyun Zhong","doi":"10.1155/ancp/6619550","DOIUrl":"10.1155/ancp/6619550","url":null,"abstract":"<p><p><b>Background:</b> Circular RNA (circRNA) is implicated in various biological processes, including the progression of gastric cancer (GC). The specific functions and underlying mechanisms of circ_0079226 in GC are unknown. <b>Methods:</b> We examined cancerous and adjacent noncancerous tissues from 25 patients with GC to evaluate circ_0079226, miR-155-5p, and forkhead transcription factor K1 (FOXK1) expression. Pearson's correlation analysis was used to assess the relationships among these RNAs. We examined their functional roles utilizing in vitro (cell cytotoxicity kit-8, wound healing, and Transwell invasion assays) and in vivo (xenograft mouse models) approaches. Molecular mechanisms were investigated using bioinformatics, dual-luciferase reporter assays, and rescue experiments, while quantitative real-time PCR, western blot, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and protein immunofluorescence (IF) were used to detect gene expression. <b>Results:</b> We found that circ_0079226 and FOXK1 levels were elevated, while miR-155-5p was reduced in GC tissues and cells. An inverse correlation existed between FOXK1 and miR-155-5p, while a direct correlation was observed between FOXK1 and circ_0079226. Circ_0079226 facilitated GC cell proliferation, migration, invasion, and in vivo tumor growth. It functions by sequestering miR-155-5p, which directly targets FOXK1. High miR-155-5p expression mitigated the effects of circ_0079226 on GC cells, and the reintroduction of FOXK1 reversed the inhibitory effects of miR-155-5p. Circ_0079226 boosts FOXK1 and its associated downstream signaling pathways, including FAK, AKT, and p-AKT, through competitive binding with miR-155-5p. <b>Conclusions:</b> In conclusion, circ_0079226 is implicated in GC cell proliferation and metastasis by modulating the miR-155-5p/FOXK1/AKT pathway, presenting it as a potential therapeutic target.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"6619550"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC1A4 Promotes Malignant Transformation of Hepatocellular Carcinoma by Activating the AKT Signaling.","authors":"Jiaoyun Zheng, Jian Gong","doi":"10.1155/ancp/1115184","DOIUrl":"10.1155/ancp/1115184","url":null,"abstract":"<p><p>Due to the difficulty in early diagnosis and the lack of treatment for advanced disease, the mortality rate of hepatocellular carcinoma (HCC) is high, and the 5-year overall survival rate is low at present. SLC1A4 is a neutral amino acid transporter, but its regulatory role and mechanism in HCC are still unclear. Through analyzing the TCGA database and clinical tissue specimens, this study uncovered the high expression of SLC1A4 in tumor tissues of HCC. Worse more, a high level of SLC1A4 may lead to a poor prognosis of HCC. Mechanically, silencing SLC1A4 inhibited the phosphorylation activation of AKT by suppressing the ubiquitin modification of AKT at lysine 63 and amino acid influx represented by D-serine, decreasing the protein level of <i>β</i>-catenin in the cell nucleus and suppressing the transcriptional activity of c-Myc and EpCAM promoters. As a result, silencing SLC1A4 inhibited the proliferation, migration, and stemness of hepatic cancer cells, which was successfully reversed by the introduction of exogenous AKT. Moreover, epithelial-mesenchymal transition (EMT) in vitro and metastasis potential in vivo of hepatic cancer cells was suppressed by the downregulated SLC1A4 level. In conclusion, SLC1A4 promotes the malignant transformation of HCC through activating signal transduction mediated by AKT. The findings in this study suggested that SLC1A4 may be a diagnostic indicator for the early HCC and a therapeutic target for the advanced HCC.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"1115184"},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11824774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDX21 Is a Potential Biomarker for Predicting Recurrence and Prognosis in Hepatocellular Carcinoma.","authors":"Chengjie Ji, Qing Zhong, Huilan Su, Xiaoli Xue, Renxiang Yang, Na Li","doi":"10.1155/ancp/1018820","DOIUrl":"10.1155/ancp/1018820","url":null,"abstract":"<p><p>DEAD-box helicase 21 (DDX21) is a conserved Asp-Glu-Ala-Asp (DEAD) box RNA helicase with multiple functions that is involved in various cellular processes and diseases. However, the role of DDX21 in the recurrence and prognosis of hepatocellular carcinoma (HCC) patients remains unknown. In the current study, we examined the protein expression of DDX21 in HCC tissues through immunohistochemical staining and analyzed the correlation between DDX21 protein expression and clinical outcome via Kaplan-Meier survival analysis. The Cox proportional hazards regression model was used to assess the interrelationships between the outcome and variable over time. Our results showed that increased expression of DDX21 protein was observed in HCC tissues compared with paracancerous tissues and was associated with advanced BCLC stage. Recurrent HCC patients had higher levels of DDX21 protein than nonrecurrent cases. Notably, DDX21 was an independent risk factor for predicting worse overall survival and recurrence-free survival in HCC patients. Furthermore, lack of DDX21 abated the growth and mobility of Hep3B cells. Taken together, our data highlight the clinical significance of DDX21 in the recurrence and prognosis of HCC patients and indicate that targeting DDX21 may represent an effective therapeutic strategy for the treatment of HCC.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"1018820"},"PeriodicalIF":2.6,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Novel Prognostic Model for Lung Adenocarcinoma Utilizing Pyroptosis-Associated LncRNAs.","authors":"Hong-Yan Bai, Tian-Tian Li, Li-Na Sun, Jing-Hong Zhang, Xiu-He Kang, Yi-Qing Qu","doi":"10.1155/ancp/4488139","DOIUrl":"10.1155/ancp/4488139","url":null,"abstract":"<p><p>Lung cancer is a highly prevalent and fatal cancer that seriously threatens the safety of people in various regions around the world. Difficulty in early diagnosis and strong drug resistance have always been difficulties in the treatment of lung cancer, so the prognosis of lung cancer has always been the focus of scientific researchers. This study used genotype-tissue expression (GTEx) and the cancer genome atlas (TCGA) databases to obtain 477 lung adenocarcinoma (LUAD) and 347 healthy individuals' samples as research subjects and divided LUAD patients into low-risk and high-risk groups based on prognostic risk scores. Differentially expressed gene (DEG) analysis was performed on 25 pyroptosis-related genes obtained from GeneCards and MSigDB databases in cancer tissues of LUAD patients and noncancerous tissues of healthy individuals, and seven genes were significantly different in cancer tissues and noncancerous tissues among them. Coexpression analysis and differential expression analysis of these genes and long noncoding RNAs (lncRNAs) found that three lncRNAs (AC012615.1, AC099850.3, and AO0001453.2) had significant differences in expression between cancer tissues and noncancerous tissues. We used Cox regression and the least absolute shrinkage sum selection operator (LASSO) regression to construct a prognostic model for LUAD patients with these three pyroptosis-related lncRNAs (pRLs) and analyzed the prognostic value of the pRLs model by the Likaplan-Meier curve and Cox regression. The results show that the risk prediction model has good prediction ability. In addition, we also studied the differences in tumor mutation burden (TMB), tumor immune dysfunction and rejection (TIDE), and immune microenvironment with pRLs risk scores in low-risk and high-risk groups. This study successfully established a LUAD prognostic model based on pRLs, which provides new insights into lncRNA-based LUAD diagnosis and treatment strategies.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"4488139"},"PeriodicalIF":2.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Glucose-Induced Senescent Fibroblasts-Derived Exosomal miR-497 Inhibits Wound Healing by Regulating Endothelial Cellular Autophagy via ATG13.","authors":"Changjiang Liu, Yuting Liu, Yifeng Yu, Siyuan Huang, Chao Sun, Dong Zhang, Aixi Yu","doi":"10.1155/ancp/8890200","DOIUrl":"10.1155/ancp/8890200","url":null,"abstract":"<p><p><b>Background:</b> Fibroblasts play a crucial role in diabetic wound healing, and their senescence is the cause of delayed wound repair. It was reported that fibroblasts can secrete exosomes that can mediate a vital role in diabetic complications. Our purpose is to examine the biological function of high glucose (HG)-induced senescent fibroblasts from the perspective of exosomes and reveal the mechanism at cellular and animal levels. <b>Methods:</b> HG-induced senescent fibroblasts were measured by senescence-associated <i>β</i>-galactosidase staining and immunofluorescence. Flow cytometry, 5-ethynyl-2'-deoxyuridine (edu), and cell counting kit 8 (CCK-8) assay were applied to detect apoptosis and cell viability. Fibroblasts and endothelial cells were cocultured, and the migration and angiogenesis abilities were detected by scratch, transwell, and tube formation assays. Exosomes were isolated and identified from fibroblasts that were treated differently. Then, the function of exosomes was investigated in cells and mice, including examining the cellular phenotype changes, detecting the autophagy levels, and evaluating the wound healing rate. Furthermore, the potential mechanism by which senescent fibroblast-derived exosomes inhibit wound healing was examined via bioinformatics, real-time quantitive polymerase chain reaction (qPCR), transfection, and dual-luciferase assays. <b>Results:</b> It illustrated that HG-induced senescent fibroblasts exhibited adverse impacts on cellular proliferation, migration, and angiogenesis of endothelial cells via secreting exosomes, and senescent fibroblast-derived exosomes (S-Exos) can delay skin wound defects in mice. Subsequent differential analysis of the GSE153214 and GSE48417 datasets elucidated that miR-497 was the biomarker in the senescent fibroblasts. Interestingly, the miR-497 levels were also elevated in S-Exos. Its overexpression can regulate human umbilical vein endothelial cell function by regulating autophagy via targeting ATG13. Furthermore, <i>in vivo</i> experiments also illustrated that miR-497 can delay wound healing and reduce autophagy. <b>Conclusions:</b> Our study demonstrated that exosomes from senescent fibroblasts can impair endothelial cell function and impede diabetic wound healing. The underlying mechanism was that fibroblast-derived exosomal miR-497 can target ATG13 to reduce autophagy, offering insight into new therapy for diabetic complications and other diseases.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"8890200"},"PeriodicalIF":2.6,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circ-ZEB1 Enhances NSCLC Metastasis and Proliferation by Modulating the miR-491-5p/EIF5A Axis.","authors":"Qi Wang, Shengying Ling, Jia Lv, Lina Wu","doi":"10.1155/ancp/5595692","DOIUrl":"10.1155/ancp/5595692","url":null,"abstract":"<p><p><b>Background:</b> Circular RNAs (circRNAs), covalently closed single-stranded RNAs, have been implicated in cancer progression. A previous investigation revealed that circ-ZEB1 is expressed abnormally in liver cancer. However, the roles of circ-ZEB1 in non-small cell lung cancer (NSCLC) are unknown. <b>Methods:</b> In this study, we used fluorescence in situ hybridization (FISH) and RT-qPCR to study circ-ZEB1 expression in NSCLC cells and tissues. A luciferase reporter assay was performed to validate downstream targets of circ-ZEB1. Transwell migration, 5-ethynyl-20-deoxyuridine (EdU), and cell counting kit-8 (CCK8) assays were performed to assess proliferation and migration. In vivo metastasis and tumorigenesis assays were also performed to investigate circ-ZEB1 functions during NSCLC. <b>Results:</b> Our results showed that circ-ZEB1 expression was increased in NSCLC tissues and cells. circ-ZEB1 downregulation suppressed NSCLC cell proliferation as well as migration in vitro and in vivo. Luciferase data confirmed EIF5A and miR-491-5p as downstream targets of circ-ZEB1. EIF5A overexpression and miR-491-5p suppression reversed NSCLC cell migration post circ-ZEB1 silencing. <b>Conclusion:</b> Our collective findings advised that circ-ZEB1 takes part in the malignant progression through regulating the miR-491-5p/EIF5A axis, highlighting its potential as an effective NSCLC therapeutic target.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"5595692"},"PeriodicalIF":2.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold Nanoparticle Inhibits the Tumor-Associated Macrophage M2 Polarization by Inhibiting m⁶A Methylation-Dependent ATG5/Autophagy in Prostate Cancer.","authors":"Yuanyuan Hao, Feng Duan, Xianning Dong, Ran Bi, Yinzhe Wang, Senqiang Zhu, Jinghai Hu","doi":"10.1155/ancp/6648632","DOIUrl":"10.1155/ancp/6648632","url":null,"abstract":"<p><p><b>Background:</b> This study aims to study how gold nanoparticles (AuNPs) function in the recruitment and polarization of tumor-associated macrophages (TAMs) in hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). <b>Methods:</b> Phorbol ester (PMA)-treated THP-1 cells were cocultured with LNCaP or PC3 cells to simulate TAMs. Macrophage M2 polarization levels were detected using flow cytometry and M2 marker determination. ATG5 expression was detected by western blotting. Luciferase reporter assay was used to analyze the N6-methyladenosine (m⁶A) site activity of ATG5 3' untranslated regions (3'-UTRs). Methylated RNA immune precipitation (MeRIP)-quantitative polymerase chain reaction (qPCR) was performed to determine the m⁶A levels at ATG5 3'-UTR. Xenograft mouse models were used to determine the function of AuNPs in vivo. <b>Results:</b> Macrophages exhibited reduced M2 polarization in both HSPC and CRPC cells after AuNP treatment which was prevented by induction of autophagy. AuNP treatment decreased the m⁶A levels in the 3'-UTR of ATG5. Mutational analysis of potential m⁶A sites within ATG5 3'-UTR revealed that these sites were required for AuNP regulation, indicating that AuNPs inhibited ATG5 levels in an m⁶A-dependent manner. The mouse model revealed that AuNPs significantly reduced the M2 polarization of TAMs in an autophagy-dependent manner in vivo. This suggests that AuNPs inhibit tumor growth in vivo partially through targeting M2 TAM. <b>Conclusion:</b> The ATG5/autophagy pathway is inhibited by AuNP treatment in an METTL3/m⁶A-dependent manner. AuNPs inhibit the TAM M2 polarization in HSPC and CRPC by inhibiting ATG5/autophagy.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2025 ","pages":"6648632"},"PeriodicalIF":2.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}