{"title":"HDAC4 Promotes Cancer Stemness in Nonsmall Cell Lung Cancer by Upregulating SLC38A2 Expression via HIF-1α to Enhance Glutamine Metabolism.","authors":"Changxian Chen, Xiaoming Jiang, Zhenwu Yao, Jiaxue Sun, Liju Zhang, Mingyu Xu, Weimin Bao, Weijun Liu","doi":"10.1155/ancp/2525721","DOIUrl":"10.1155/ancp/2525721","url":null,"abstract":"<p><strong>Background and purpose: </strong>The malignant progression of nonsmall cell lung cancer (NSCLC) is closely related to cancer stemness. Histone deacetylase 4 (HDAC4) plays a regulatory role in lung cancer, but its effect on NSCLC stemness remains unclear. This study aimed to investigate the role and mechanism of HDAC4 in NSCLC stemness.</p><p><strong>Methods: </strong>In this study, a tumor-bearing model was established by subcutaneously injecting A549 cells into the right dorsal side of nude mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry were used to measure gene and protein expression levels. Flow cytometry, sphere formation assays, and Transwell experiments were employed to assess cancer cell stemness, migration, and invasion. Additionally, a kit was used to measure changes in glutamine metabolism-related indicators.</p><p><strong>Results: </strong>In this study, we found that knocking down HDAC4 expression inhibited the expression of SRY-box transcription factor 2 (SOX2), octamer-binding transcription factor 4 (OCT4), and nanog homeobox (NANOG) in A549 cells; it also reduced the proportions of CD133- and CD44-positive cells and suppressed their sphere formation, cell migration, and invasion abilities. Furthermore, HDAC4 knockdown inhibited glutamine uptake, glutamate production, α-ketoglutarate levels, and glutaminase (GLS) activity. Notably, treatment with the additional glutamine metabolism inhibitor CB-839 attenuated the promoting effects of HDAC4 overexpression on the stemness, migration, and invasion of A549 cells. In addition, HDAC4 promoted the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and solute carrier family 38 member 2 (SLC38A2); after overexpressing HIF-1α, the inhibitory effect of HDAC4 knockdown on SLC38A2 expression in A549 cells was weakened.</p><p><strong>Conclusion: </strong>Our study reveals a critical mechanism by which HDAC4 enhances glutamine metabolism through upregulation of HIF-1α expression to promote SLC38A2 expression, thereby driving NSCLC stemness and progression.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2026 1","pages":"e2525721"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070397","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}
Anna Su, Yunfei Zhao, Zongze Gu, Laxin Sabitjan, Gulimire Adili, Xun Li, Weiling Yu
{"title":"The Role of Chemokine-Related Genes in Diffuse Large B-Cell Lymphoma Prognosis and Tumor Microenvironment Characteristics.","authors":"Anna Su, Yunfei Zhao, Zongze Gu, Laxin Sabitjan, Gulimire Adili, Xun Li, Weiling Yu","doi":"10.1155/ancp/6659091","DOIUrl":"10.1155/ancp/6659091","url":null,"abstract":"<p><strong>Background: </strong>Diffuse large B-cell lymphoma (DLBCL) is a malignant neoplasm characterized by intermediate to high aggressiveness and heterogeneity. Chemokines and their receptors are involved in various antitumor and protumor immune processes in vivo and influence patient prognosis and treatment response. Therefore, investigating the potential associations between chemotactic cytokine-related genes (CCRGs) and prognosis, as well as the immune microenvironment in DLBCL holds significant importance.</p><p><strong>Methods: </strong>Differentially expressed and prognosis-related CCRGs in DLBCL were extracted from the GEO database. A prognostic risk model was constructed using Lasso-Cox regression analysis, followed by internal and external cohort validation to assess the model's predictive independence. This risk model was then applied to immunological analysis, enrichment analysis, and drug prediction analysis. Single-cell sequencing was employed to investigate the correlation between genes in the prognostic model and immune cell types.</p><p><strong>Results: </strong>We identified 23 prognosis-related CCRGs and revealed two CCRG-associated subtypes exhibiting distinct immune processes. Subsequently, a six-gene prognostic model was established using LASSO-Cox regression analysis. Univariate and multivariate prognostic analyses demonstrated that the risk model serves as an independent prognostic factor, and both the CCRG prognostic model and signature genes showed a significant correlation with the tumor immune microenvironment (TIME).</p><p><strong>Conclusion: </strong>The CCRG risk model proposed in this study can accurately and stably predict the prognosis of DLBCL patients and is closely associated with the TIME, providing new targets and theoretical support for DLBCL patients.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2026 1","pages":"e6659091"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13131906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822888","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":"Correction to \"Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway\".","authors":"","doi":"10.1155/ancp/9838646","DOIUrl":"https://doi.org/10.1155/ancp/9838646","url":null,"abstract":"","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2026 1","pages":"e9838646"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844866","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":"BRAF Mutation Affects Intratumor Heterogeneity in Papillary Thyroid Carcinoma.","authors":"Ying-Er Feng, Cun-Jie Wang","doi":"10.1155/ancp/8843563","DOIUrl":"10.1155/ancp/8843563","url":null,"abstract":"<p><strong>Background: </strong>Intratumor heterogeneity (ITH) plays an important role in patients' clinical outcomes. The prognostic impact of ITH and its influencing factors is unclear in papillary thyroid carcinoma (PTC), which deserves further investigation.</p><p><strong>Methods: </strong>The Mutation Annotation Format (MAF) and clinical features were collected from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) cohort. We first assessed the influence of ITH on the prognosis of patients. We used the Mutant Allele Tumor Heterogeneity score to evaluate and represent ITH. Then we explored the potential factors associated with ITH. Finally, we predicted possible pathways involved in ITH.</p><p><strong>Results: </strong>Among 4 prognostic outcomes, higher ITH was mainly related to poor disease-free interval (DFI) (HR = 2.64, p = 0.01), and ITH had potential value for predicting DFI. Further, we identified BRAF mutation and thyroid differentiation score (TDS) as key factors independently influencing ITH (all p < 0.05), especially TDS, which had a favorable ability and obtained good net benefit in predicting ITH. TDS maintained a stable negative effect on ITH. In contrast, BRAF mutation positively correlated with ITH in univariable regression (β = 0.196). Through performing sensitivity, regression, subgroup, interaction effect, and mediation analyses, we identified that TDS played a suppression effect in the impact of BRAF mutation on ITH. Finally, we revealed that the propionate metabolism pathway was most strongly associated with ITH.</p><p><strong>Conclusions: </strong>ITH is associated with DFI in patients with PTC and deserves more attention. TDS and BRAF mutation are the key influencing factors of ITH, but TDS exerts a suppression effect on the impact of BRAF mutation on ITH.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2026 1","pages":"e8843563"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147965323","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":"Identification of Potential Therapeutic Agents for Primary Amebic Meningoencephalitis Using Text Mining and Bioinformatics Analyses.","authors":"Eun Jung Sohn, Hyeonseo Jo, Kun Taek Park","doi":"10.1155/ancp/5577830","DOIUrl":"10.1155/ancp/5577830","url":null,"abstract":"<p><p>Naegleria fowleri, the brain-eating ameba, causes primary amebic meningoencephalitis (PAM), a fatal infectious disease that affects the central nervous system (CNS). We aimed to evaluate the functions and potential drugs targeting PAM using text mining and bioinformatics analyses. PAM-associated genes were identified using a disease database and mined from literature. To identify candidate drugs targeting PAM, 218 genes were analyzed using PanDrugs, drug Manually Annotated Targets and Drugs Online Resource (MATADOR), and the drug Comparative Toxicogenomics Database (CTD) by text mining. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional analyses were performed to examine the mechanism of action of PAM. The GO functions of genes involved in PAM identified by text mining were leukocyte differentiation and the regulation of cytokine production. Disease-related PAM analyses indicated association with Zellweger syndrome, peroxisomal disease, periodontitis, and leishmaniasis. KEGG enrichment included pathways related to inflammatory bowel disease, malaria, interleukin (IL)-17 signaling pathway, Yersinia infection, Chagas disease, amebiasis, rheumatoid arthritis, pathogenic Escherichia coli infection, lipids, atherosclerosis, and peroxisomes. In addition, arsenic trioxide, bortezomib, dasatinib, bosutinib, bevacizumab, paclitaxel, midostaurin, tamoxifen, copanlisib, and pazopanib were identified as potential drugs targeting PAM using PanDrugs software. Our analyses revealed that text mining-related PAM genes were enriched in several pathways, such as peroxisomes and protein localization. We suggest that PAM is linked to other diseases, such as Zellweger's syndrome, leishmaniasis, and periodontitis, and provide potential drugs for effective treatment.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2026 1","pages":"e5577830"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437201","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":"RETRACTION: MicroRNA-520a Suppresses Pathogenesis and Progression of Non-Small-Cell Lung Cancer through Targeting the RRM2/Wnt Axis.","authors":"Analytical Cellular Pathology","doi":"10.1155/ancp/9864065","DOIUrl":"10.1155/ancp/9864065","url":null,"abstract":"","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2026 1","pages":"e9864065"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437157","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":"PYCR1 Downregulation Induces Autophagy Dependent Apoptosis Through Inhibiting PI3K/AKT/mTOR Axis in Human Hepatocellular Carcinoma Cells.","authors":"Junli Zhang, Yachao Hou, Xinxin Jin, Biao Gu, Wenjuan Wu","doi":"10.1155/ancp/3662809","DOIUrl":"10.1155/ancp/3662809","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a global malignant tumor type. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a metabolic enzyme that exhibits pro-tumor properties in cancer progression. However, the exact molecular mechanism of PYCR1 in HCC progression is still unclear.</p><p><strong>Methods: </strong>CCK8, EdU, and Transwell assays were used to measure the proliferation, migration, and invasion of HCC cells, respectively. Immunostaining and flow cytometry were used to detect cellular autophagy and apoptosis.</p><p><strong>Results: </strong>The downregulation of PYCR1 can inhibit the survival, proliferation, migration, and invasion of HCC cells. At the same time, downregulation of PYCR1 induces autophagy and subsequently activates cell apoptosis. Therefore, we pretreated HCC cells with mTOR activators or inhibitors to inhibit or promote autophagy, leading to an inhibition or an increase in apoptosis. Simultaneously, the PI3K activators or inhibitors to activate or inhibit the PI3K/AKT/mTOR pathway also lead to inhibition or activation of autophagy and apoptosis.</p><p><strong>Conclusion: </strong>The downregulation of PYCR1 induces autophagy-dependent apoptosis in HCC cells by inhibiting the PI3K/AKT/mTOR pathway, revealing a novel mechanistic link in HCC pathophysiology.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2026 1","pages":"e3662809"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437224","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":"Integrative Pan-Cancer Characterization of lncRNA UPK1A-AS1 and Its Role in Hypoxia-Associated Sorafenib Resistance in Hepatocellular Carcinoma.","authors":"Ze-Kai Li, Min-Rui Luo, Shu-Jie Fang, Yi-Da Wu, Quan-Hui Hu, Dong-Yan Zhang","doi":"10.1155/ancp/1554526","DOIUrl":"10.1155/ancp/1554526","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) are emerging as critical regulators of tumor initiation and progression through transcriptional and posttranscriptional mechanisms. UPK1A antisense RNA 1 (UPK1A-AS1), a cancer-associated lncRNA, has been reported to participate in oncogenic processes; however, its overall landscape across human malignancies and its biological role in therapy resistance remain poorly understood. Given the increasing importance of identifying functional lncRNAs with prognostic and therapeutic potential, this study presents a comprehensive multiomics characterization of UPK1A-AS1 and its experimental validation in hepatocellular carcinoma (HCC). We integrated datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), the cancer immunology data engine (CIDE), and the cBioPortal for cancer genomics (cBioPortal) to systematically assess its expression pattern, genomic alterations, clinical significance, and immunological associations. Our analyses revealed that UPK1A-AS1 is significantly upregulated in multiple tumor types, with copy-number amplification as the predominant genomic alteration driving its overexpression. Elevated UPK1A-AS1 expression was correlated with advanced disease stage, poor differentiation, immune exclusion, and unfavorable prognosis, supporting its potential as a cancer type-dependent biomarker. In parallel, functional studies demonstrated that hypoxia transcriptionally induces UPK1A-AS1 in HCC, where it promotes sorafenib resistance by suppressing apoptosis. Silencing UPK1A-AS1 restored apoptotic and enhanced sorafenib efficacy both in vitro and in vivo. Collectively, our findings suggest that UPK1A-AS1 is a hypoxia-inducible oncogenic lncRNA that plays dual roles in cancer, with cancer type-dependent associations with progression and immune modulation across malignancies and mechanistically mediating hypoxia-associated drug resistance in HCC.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2026 1","pages":"e1554526"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867332","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}