Molecular and Cellular Probes最新文献

{"title":"DNMT3A triggers tumorigenesis of non-small cell lung cancer through regulation of SLIT2 methylation and SLIT2-mediated macrophage M1/M2 polarization","authors":"Tian-xing Ni ,&nbsp;Jia-bo Shen","doi":"10.1016/j.mcp.2025.102033","DOIUrl":"10.1016/j.mcp.2025.102033","url":null,"abstract":"<div><h3>Background</h3><div>Increased DNA methylation is prevalent in human cancers and is one of the important characteristics of tumors. This research aims to investigate the molecular mechanisms that involve DNMT3A and DNA methylation modification of SLIT2 in non-small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>Gene expression was examined using Western blot assay, immunohistochemistry and RT-qPCR. Cell viability and motility were measured by CCK-8, colony formation, Transwell and wound healing assays. Macrophage M1/M2 polarization was assessed through a flow cytometry assay. Using ELISA, the secretion levels of inflammatory factors by macrophage M1/M2 polarization were determined. ChIP, qMSP and dual-luciferase reporter assays confirmed the relationship between DNMT3A and SLIT2.</div></div><div><h3>Results</h3><div>High expression of DNMT3A was observed in NSCLC patients, enhancing NSCLC cell viability and metastasis. Mechanically, DNMT3A was identified to target SLIT2. DNMT3A inhibited SLIT2 expression through DNA methylation modification in NSCLC. Further, overexpression of SLIT2 impeded M2 polarization of macrophages in NSCLC. And SLIT2 overexpression hindered NSCLC tumor growth <em>in vivo</em> by affecting macrophage M2 polarization. Finally, DNMT3A was found to promote the progression of NSCLC by downregulating SLIT2.</div></div><div><h3>Conclusion</h3><div>DNMT3A promotes the progression of NSCLC via regulating methylation modification of SLIT2 and SLIT2-mediated macrophage M1/M2 polarization.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"82 ","pages":"Article 102033"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional regulation of tumor suppressor gene RASSF1A by HBx","authors":"Yanhong Kang ,&nbsp;Wei Li ,&nbsp;Junfeng Wei ,&nbsp;Lin Yang ,&nbsp;Yi Kang","doi":"10.1016/j.mcp.2025.102034","DOIUrl":"10.1016/j.mcp.2025.102034","url":null,"abstract":"<div><h3>Introduction</h3><div>The occurrence of liver cancer in China is primarily attributed to chronic hepatitis B virus (HBV) infection. HBV X protein (HBx) has emerged as a significant carcinogenic driver in HBV-related liver cancer. However, the underlying mechanism by which HBx contributes to liver cancer development is not fully understood.</div></div><div><h3>Methods</h3><div>This study investigated HBx's role in regulating the tumor-suppressor gene RASSF1A. Firstly, the RASSF1A plasmid was constructed using a luciferase reporter system. The dual luciferase assay system detected HBx's effect on RASSF1A promoter activity. Western blotting and quantitative PCR methods measured HBx's impact on RASSF1A protein and mRNA expression. Chip was used to test the binding of HBx and SP1. CCK8, transwell, flow cytometry were used to detect the effect of RASSF1A on HCC proliferation. Methylation-specific PCR analyzed HBx's effect on RASSF1A methylation.</div></div><div><h3>Results</h3><div>Our results show that HBx significantly enhances RASSF1A promoter activity in an SP1 binding site-dependent manner. When only one SP1 binding site remained, HBx's effect was abolished. RASSF1A can inhibit HCC proliferation. Both mRNA and protein expression levels of RASSF1A were lower in HBx-expressing THLE-2 cells than in control cells, correlating with higher RASSF1A promoter methylation.</div></div><div><h3>Conclusion</h3><div>These findings suggest HBx enhances RASSF1A promoter activity and upregulates transcription via SP1, potentially preceding RASSF1A promoter methylation. This study provides new insights into HBx's regulation of the tumor suppressor gene RASSF1A in HBV-related liver cancer.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"82 ","pages":"Article 102034"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrodin promotes osteogenic differentiation by stimulating the Wnt/β-catenin signaling pathway","authors":"Wei Jiang ,&nbsp;Lifeng Zhang ,&nbsp;Wenshan Shan ,&nbsp;Zuomeng Wu ,&nbsp;Jiaqi Wang ,&nbsp;Cailiang Shen","doi":"10.1016/j.mcp.2025.102035","DOIUrl":"10.1016/j.mcp.2025.102035","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis is a common disease that can lead to fracture as well as various skeletal symptoms and is a global health problem. Traditional Chinese medicine (TCM) may offer novel approaches for treating osteoporosis. Our study aimed to investigate the osteogenic potential and underlying mechanisms of gastrodin in promoting osteogenic differentiation.</div></div><div><h3>Methods</h3><div>By combining network pharmacology and bioinformatics, we conducted experiments to inspect cell viability, Alkaline Phosphatase (ALP) viability, and Alizarin red staining (ARS) and investigate the expression profiles of genes and proteins relevant to osteogenesis, including β-catenin, Runt-related transcription factor 2 (Runx2), Low Density Lipoprotein Receptor-Related Protein 5 (LRP5) and Glycogen synthase kinase-3 beta (GSK-3β). Statistical analysis was used for validation.</div></div><div><h3>Results</h3><div>Network pharmacology and bioinformatics analyses revealed that gastrodin might influence osteogenic differentiation. The experimental results revealed that gastrodin had no toxic effects and was able to promote ALP activity and stimulate osteogenic differentiation of Mouse Calvaria-derived Osteoblastic Cell Line.</div><div>(MC3T3-E1) cells. Subsequent network pharmacology and bioinformatics studies revealed that gastrodin might affect osteogenic differentiation through the Wnt/β-catenin signaling pathway. The results revealed that gastrodin influenced osteogenic differentiation genes and protein expression, including the upregulation of β-catenin, Runx2, and LRP5 and the downregulation of GSK-3β, and Dickkopf-1 (DKK-1) inhibited its promotion.</div></div><div><h3>Conclusion</h3><div>Gastrodin enhances the Wingless (Wnt)/β-catenin signaling pathway by increasing β-catenin accumulation and nuclear migration as well as decreasing GSK-3β, which increases Runx2 expression, consequently encouraging MC3T3-E1 cell osteogenic differentiation, and may be applied as a potential drug for osteoporosis therapy and prevention.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"82 ","pages":"Article 102035"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and identification Hub genes associated with immune cell infiltration and critical biomarkers in osteosarcoma","authors":"Xin Song ,&nbsp;Sihao Chen ,&nbsp;Junning Cheng ,&nbsp;Haiyu Li ,&nbsp;Ruixin Wu ,&nbsp;Min Yan ,&nbsp;Min Wang ,&nbsp;Jie Li ,&nbsp;Aishun Jin ,&nbsp;Wang Wang","doi":"10.1016/j.mcp.2025.102031","DOIUrl":"10.1016/j.mcp.2025.102031","url":null,"abstract":"<div><h3>Purpose</h3><div>Osteosarcoma (OS) exhibits limited immune cell infiltration that directly contributes to poor prognosis. This study sought to screen and identify pivotal biomarkers of OS immune infiltration and early diagnosis of OS.</div></div><div><h3>Methods</h3><div>The immune cell infiltration profiles with transcriptome sequencing data from 88 OS samples were explored with CIBERSORT algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network analyses were applied to identify hub genes, with the expressions confirmed by dual immunofluorescence in 50 OS samples. The new biomarker gene HTRA1 were examined by immunohistochemistry and validated by the Immune score and immune gene expression profile analyses. The impact of HTRA1 on OS prognosis was verified by Least absolute shrinkage and selection operator (LASSO) regression analysis. The biological effect of HTRA1 was characterized in MG63 cells.</div></div><div><h3>Result</h3><div>CD8⁺ T cells, activated memory CD4⁺ T cells and plasma cells were positively correlated with the prognosis of OS. Hub genes <em>CCL5</em>, <em>CXCL9</em>, <em>CXCL13</em>, and <em>HTRA1</em>, exhibited positive correlation with the infiltration of both CD8⁺ T cells and CD4⁺ T cells. HTRA1 expression was reduced in osteosarcoma tissues, which was positively correlated with immune scores and the expressions of immune-related genes. High levels of HTRA1 were associated with favorable OS prognosis, and could negatively impacted MG63 malignant characteristics.</div></div><div><h3>Conclusion</h3><div><em>CCL5</em>, <em>CXCL9</em>, <em>CXCL13,</em> and <em>HTRA1</em> were OS hub genes positively correlate with CD8⁺ T cell and CD4⁺ T cell infiltrations. HTRA1 can serve as an underlying biomarker for the prognosis and immunotherapy of OS.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"82 ","pages":"Article 102031"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal lncRNA profiles in patients with HFrEF: Evidence for KLF3-AS1 as a novel diagnostic biomarker","authors":"Lei Wang ,&nbsp;Yanan Zhang ,&nbsp;Jiapu Wang ,&nbsp;Xiao Jiang ,&nbsp;Gang Wang ,&nbsp;Haixiong Wang ,&nbsp;Yan Shu ,&nbsp;Han Huiyuan","doi":"10.1016/j.mcp.2025.102032","DOIUrl":"10.1016/j.mcp.2025.102032","url":null,"abstract":"<div><h3>Background</h3><div>Serum exosomal long noncoding RNAs (lncRNAs) have not been studied extensively as biomarkers in heart failure (HF) with reduced ejection fraction (HFrEF). We compared lncRNA expression in patients with HFrEF hospitalized for acute HF with that in healthy individuals to identify differentially expressed exosomal lncRNAs. Furthermore, we explored the clinical value of exosomal KLF3-AS1 in diagnosing HF and investigated its role in cardiac hypertrophy.</div></div><div><h3>Method</h3><div>Exosomes were isolated from patients with HFrEF and healthy individuals. We performed microarray analysis of differentially expressed lncRNAs and genes (DELs and DEGs, respectively) associated with HF. Protein-protein interaction (PPI), lncRNA-mRNA-KEGG pathway, and interaction networks between lncRNAs and RNA-binding proteins (RBPs) were developed. Expression patterns were verified using qRT-PCR. The diagnostic applicability of exosomal lncRNAs in HF was quantified by plotting receiver operating characteristic (ROC) curves. The size of the cardiomyocytes was evaluated using α-actinin immunostaining.</div></div><div><h3>Results</h3><div>In total, 138 DELs and 1132 DEGs were identified. PPI network analysis identified <em>INS</em>, <em>CTNNB1</em>, and <em>CAT</em> as the most prominent hub genes, whereas <em>MDM2</em>, <em>MYH6</em>, <em>ENAH</em>, and KLF3-AS1 were significantly enriched in the RBP interaction network. In the validation phase, patients with HFrEF exhibited a significant increase in KLF3-AS1 expression compared with healthy individuals. Exosomal KLF3-AS1 had an area under the ROC curve of 0.861. Functionally, KLF3-AS1 overexpression reduced Ang II-induced cardiac hypertrophy <em>in vitro</em>.</div></div><div><h3>Conclusion</h3><div>Our results elucidated the exact patterns of circulating exosomal mRNAs and lncRNA expression in patients with HFrEF hospitalized for acute HF. Moreover, the high expression of exosomal KLF3-AS1 is a potential diagnostic biomarker for HFrEF.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"82 ","pages":"Article 102032"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down-regulated circ_0001853 inhibits lipopolysaccharide-induced endometritis progression via sponging miR-34c-5p","authors":"Qian Xu,&nbsp;Ailing Peng,&nbsp;Liyun Zhao,&nbsp;Li Wang","doi":"10.1016/j.mcp.2025.102023","DOIUrl":"10.1016/j.mcp.2025.102023","url":null,"abstract":"<div><h3>Background</h3><div>To investigate the diagnostic value and mechanism of action of circular RNA (circ_) circ_0001853 and microRNA (miR) miR-34c-5p in patients with endometritis.</div></div><div><h3>Methods</h3><div>189 patients with endometritis and 176 healthy individuals were included in this study. Venous blood serum was collected from the study subjects and stored temporarily at −80 °C. Real-time quantitative chain polymerase reaction (RT-qPCR) was used to detect circ_0001853 and miR-34c-5p expression, and receiver operating characteristic (ROC) curves assessed the diagnostic value of both in predicting endometritis. Cell counting kit (CCK8) observed cell proliferation, flow cytometry recorded apoptosis, enzyme linked immunosorbent assay (ELISA) monitored inflammatory factor expression, and dual luciferase reporter assay and RNA immunoprecipitation (RIP) verified the relationship between circ_0001853 and miR-34c-5p targeting interactions.</div></div><div><h3>Results</h3><div>High levels of circ_0001853 and low levels of miR-34c-5p were present in endometritis patients, and they were negatively correlated. Both circ_0001853 and miR-34c-5p alone or in combination had diagnostic value in predicting the progression of endometritis. Transfection of si-circ_0001853 promoted cell proliferation and reduced apoptosis and cellular inflammation levels induced by lipopolysaccharide (LPS) stimulation. There was a direct reciprocal targeting relationship between miR-34c-5p and circ_0001853, and the use of miR-34c-5p inhibitor resisted silencing circ_0001853 promoted cell proliferation and increased the number of apoptotic cells and cellular inflammation levels.</div></div><div><h3>Conclusions</h3><div>circ_0001853 is involved in endometritis progression through miR-34c-5p, i.e., low circ_0001853 promotes miR-34c-5p-induced proliferation of epithelial cells, reduces apoptosis, and suppresses inflammation levels, preventing disease progression.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102023"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BUB1-deficiency suppresses kidney renal clear cell carcinoma progression via the PI3K/Akt pathway: A bioinformatics-oriented validating study","authors":"Xiaolin Zi ,&nbsp;Jinpeng Ma ,&nbsp;Xiaoxia Li ,&nbsp;Honglei Wang ,&nbsp;Yuchen Bao ,&nbsp;Tao Deng ,&nbsp;Xueli Yuan","doi":"10.1016/j.mcp.2025.102024","DOIUrl":"10.1016/j.mcp.2025.102024","url":null,"abstract":"<div><div>Although great advances have been reached in the diagnosis, treatment and prognosis of kidney renal clear cell carcinoma (KIRC), the advancement of therapeutic strategies for KIRC in clinical practices have been seriously limited due to its unknown molecular mechanisms. To resolve this issue, through analyzing the datasets from the online UCSC database, a novel BUB1 gene was found to be elevated in the cancerous tissues compared to their normal tissues of KIRC, and and KIRC patients with high-expressed BUB1 tended to have a worse prognosis. The subsequent experiments validated that BUB1 protein was located in both nucleus and cytoplasm of KIRC cells, and the expression levels of BUB1 gene were significantly elevated in KIRC tissues and cells, in contrast to their normal counterparts. Loss-of-function experiments verified that knockdown of BUB1 suppressed cell proliferation, mobility, epithelial-mesenchymal transition (EMT) and tumor growth, whereas induced apoptotic cell death in the KIRC cells <em>in vitro</em> and <em>in vivo</em>. In addition, bioinformatics analysis predicted that the differentially-expressed genes (DEGs) in the BUB1-deficient cohorts were enriched in the cell division-related PI3K/Akt signal pathway, and we evidenced that silencing of BUB1 was capable of inactivating the downstream PI3K/Akt signal pathway. Of note, deficiency of BUB1-induced suppressing effects on the malignant phenotypes in KIRC cells were all reversed by co-treating cells with PI3K/Akt pathway activator 740Y-P. Furthermore, it was found that the expression status of BUB1 gene were related with epigenetic modifications, immune infiltration and immunotherapy responses in KIRC. Collectively, silencing of BUB1 inhibited the progression of KIRC through inactivating the downstream PI3K/Akt signal pathway, and BUB1 gene could be potentially used as biomarkers for the diagnosis and treatment of KIRC in clinic.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102024"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential gene expression in uterine endometrioid cancer cells and adjusted normal tissue","authors":"Dominik Kodada ,&nbsp;Dominik Hadžega ,&nbsp;Patrik Krumpolec ,&nbsp;Nikola Janoštiaková ,&nbsp;Gabriela Bľandová ,&nbsp;Pavol Janega ,&nbsp;Zuzana Ballová ,&nbsp;Erik Dosedla ,&nbsp;Gabriel Minárik ,&nbsp;Vanda Repiská","doi":"10.1016/j.mcp.2025.102027","DOIUrl":"10.1016/j.mcp.2025.102027","url":null,"abstract":"<div><div>Endometrial cancer is a significant public health concern with rising incidence rates globally. Understanding the molecular mechanisms underlying this disease is crucial for developing effective therapeutic strategies. Our study aimed to characterize transcriptional changes in endometrial cancer tissues compared to adjusted healthy tissue. Using RNA sequencing, we identified 2483 differentially expressed genes (DEGs), including protein-coding genes, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs). Notably, several known cancer-related genes were differentially expressed, such as <em>MYC</em>, <em>AKT3</em>, <em>CCND1</em>, and <em>CDKN2A</em>. Pathway analysis revealed significant alterations in cell cycle regulation, several signaling pathways, and metabolic processes. These findings provide valuable insights into the molecular pathways dysregulated in endometrial cancer. Our results may contribute to the development of novel therapeutic targets and biomarkers for this disease.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102027"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinicopathologic and prognostic value of CD44 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis","authors":"Elmira Alaei ,&nbsp;Najma Farahani ,&nbsp;Sima Orouei ,&nbsp;Mina Alimohammadi ,&nbsp;Salman Daneshi ,&nbsp;Tahoora Mousavi ,&nbsp;Behnaz Mahmoodieh ,&nbsp;Afshin Taheriazam ,&nbsp;Payman Rahimzadeh ,&nbsp;Mehrdad Hashemi","doi":"10.1016/j.mcp.2025.102028","DOIUrl":"10.1016/j.mcp.2025.102028","url":null,"abstract":"<div><h3>Background</h3><div>CD44 is a promising target in the prognosis and treatment of non-small cell lung cancer (NSCLC). The study deals with systematic review and meta-analysis to determine the association between CD44 overexpression and survival and clinicopathological characteristics in NSCLC patients.</div></div><div><h3>Methods</h3><div>We used the databases Google Scholar, Web of Science, PubMed, Scopus, EMBASE, and Cochrane to conduct a systematic search of English-language literature published up to September 2023. The eligible studies were retrieved on CD44 expression, clinicopathological characteristics in NSCLC patients, and reported survival rates. The Cochran's and Higgins I² tests were used to measure heterogeneity across the included studies. P &lt; 0.05 was considered statistically significant in all cases. The sources of heterogeneity across the included studies were identified using subgroup analysis on histology (SCC, ADC, and LCC), tumor differentiation (well, moderate, and poor), TMN stage (I/II/III/IV), OS, and lymph node metastasis (negative and positive). All statistical analyses were carried out using meta-analysis (CMA) software.</div></div><div><h3>Results</h3><div>The final analysis for prognostic significance and clinicopathological features on 3681 participants from 25 eligible studies. The pooled event rate of overexpression CD44 for overall survival in NSCLC was 38 % and was related to SCC with 76.6 %. Furthermore, subgroup analysis revealed a link between CD44 overexpression and moderate tumor differentiation (41.8 %). There was a substantial difference in CD44 overexpression in males, with 69.3 % (95 % CI: 64.3–73.9 %, I² = 88.25 %) versus 31.5 % (95 % CI: 26.7–36.8 %, I² = 92.15 %) in females. However, no significant relationship was observed between CD44 overexpression and TMN stages/lymph node metastasis.</div></div><div><h3>Conclusion</h3><div>The meta-analysis demonstrated that CD44 is an effective prognostic factor for NSCLC. Overexpression of CD44 has been linked to moderate tumor differentiation, SCC tumor histology, and a worse survival rate. However, no substantial relationship was found between CD44 and metastasis or TMN stages. Large-scale prospective research is required to validate CD44's clinical value as an unbiased prognostic indicator.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102028"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis of intracellular RNA granules and small extracellular vesicles: Unmasking their overlap in a cell model of Huntington's disease","authors":"Deepti Kailash Nabariya ,&nbsp;Lisa Maria Knüpfer ,&nbsp;Patrick Hartwich ,&nbsp;Manuela S. Killian ,&nbsp;Florian Centler ,&nbsp;Sybille Krauß","doi":"10.1016/j.mcp.2025.102026","DOIUrl":"10.1016/j.mcp.2025.102026","url":null,"abstract":"<div><div>Huntington's disease (HD) arises from the abnormal expansion of a CAG repeat in the <em>HTT</em> gene. The mutant CAG repeat triggers aberrant RNA-protein interactions and translates into toxic aggregate-prone polyglutamine protein. These aberrant RNA-protein ineractions also seed the formation of cytoplasmic liquid-like granules, such as stress granules. Emerging evidence demonstrates that granules formed via liquid-liquid phase separation can mature into gel-like inclusions that persist within the cell and may act as precursor to aggregates that occur in patients' tissue. Thus, deregulation of RNA granules is an important component of neurodegeneration. Interestingly, both the formation of intracellular membrane-less organelles like stress granules and the secretion of small extracellular vesicles (sEVs) increase upon stress and under disease conditions. sEVs are lipid membrane-bound particles that are secreted from all cell types and may participate in the spreading of misfolded proteins and aberrant RNA-protein complexes across the central nervous system in neurodegenerative diseases like HD. In this study, we performed a comparative transcriptomic analysis of sEVs and RNA granules in an HD model. RNA granules and sEVs were isolated from an inducible HD cell model. Both sEVs and RNA granules were isolated from induced (HD) and non-induced (control) cells and analyzed by RNA sequencing. Our comparative analysis between the transcriptomics data of HD RNA granules and sEVs showed that: (I) intracellular RNA granules and extracellular RNA vesicles share content, (II) several non-coding RNAs translocate to RNA granules, and (III) the composition of RNA granules and sEVs is affected in HD cells. Our data showing common transcripts in intracellular RNA granules and extracellular sEVs suggest that formation of RNA granules and sEV loading may be related. Moreover, we found a high abundance of lncRNAs in both control and HD samples, with several transcripts under REST regulation, highlighting their potential role in HD pathogenesis and selective incorporation into sEVs. The transcriptome cargo of RNA granules or sEVs may serve as a source for diagnostic strategies. For example, disease-specific RNA-signatures of sEVs can serve as biomarker of central nervous system diseases. Therefore, we compared our dataset to transcriptomic data from HD patient sEVs in blood. However, our data suggest that the cell-type specific signature of sEV-secreted RNAs as well as their high variability may make it difficult to detect these biomarkers in blood.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102026"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}