Carcinogenesis最新文献

{"title":"Establishing a new-onset diabetes-related metabolism signature for predicting the prognosis and immune landscape in pancreatic cancer.","authors":"Yilei Yang, Luyao Liu, Haochen Cui, Bin Cheng, Wang Peng, Ronghua Wang, Jinlin Wang, Wei Chen, Mengdie Cao, Yanling Li, Jingwen Liang, Shiru Chen, Shuya Bai, Yuchong Zhao","doi":"10.1093/carcin/bgae072","DOIUrl":"10.1093/carcin/bgae072","url":null,"abstract":"<p><p>New-onset diabetes (NOD) is a common condition among patients with pancreatic adenocarcinoma (PAAD) and is related to poor clinical outcomes. The potential impact of NOD on PAAD progression and the tumor microenvironment remains unclear. Here, we revealed that NOD in PAAD was associated with metabolic disorders. Utilizing three machine-learning algorithms, an NOD-related metabolism signature (NRMS) was established. Validated in three independent cohorts, patients with a high NRMS score exhibited a worse prognosis. Moreover, an elevated NRMS score was associated with an immunosuppressive microenvironment and diminished response to immunotherapy. Further experiments demonstrated that ALDH3A1, a key feature in NRMS, was significantly upregulated in tissues from PAAD patients with NOD and played a crucial role in tumor progression and immune suppression. Our findings highlight the potential of NRMS as a prognostic biomarker and an indicator of immunotherapy response for patients with PAAD.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Susceptibility to Lung Squamous Cell Carcinoma: New Insights on 9q33.2 Variants and Tobacco Smoking.","authors":"Huimin Ma, Guoqing Wang, Sunan Miao, Chen Jin, Jiaying Cai, Wenjing Ge, Chang Zhang, Erbao Zhang, Hongxia Ma, Meng Zhu","doi":"10.1093/carcin/bgaf018","DOIUrl":"https://doi.org/10.1093/carcin/bgaf018","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) have identified over 60 susceptibility loci for lung cancer, yet the biological mechanisms underlying these associations remain largely unknown, particularly for lung squamous cell carcinoma (LUSC). Here, we integrated data from 3890 LUSC cases and 13328 controls of Chinese descent, and performed a conditional analysis to explore independent genetic variants and analyzed the interaction between the genetic variants and smoking. Our study was the first to identify a specific association between genetic variants in the 9q33.2 region and increased risk of LUSC in smokers. After adjusting for the tag SNP rs4573350 in 9q33.2, no additional significant genetic variants were found. However, significant additive (RERI=1.66, 95%CI: 1.17-2.22, AP=0.26, 95%CI: 0.19-0.33) and multiple interactions (OR=1.30, 95%CI: 1.08-1.56, P=5.40×10-3) were observed between rs4573350 and smoking. Compared to nonsmokers with the CC genotype, smokers with the CT/TT genotype showed an increased risk of 6.29-fold (95%CI: 5.46-7.23, P=2.00×10-16). Functional annotation identified rs4573350 as the strongest functional variant within the linkage disequilibrium block. Biological experiments confirmed that the combined exposure to the T allele of rs4573350 and cigarette smoke extract promotes the expression of the ZBTB26 by modulating the binding ability of the transcription factor FOXA1. Furthermore, ZBTB26 was found to regulate tumorigenesis of LUSC both in vitro and in vivo by affecting the expression of PCNA, which is involved in cell cycle and promotes tumorigenesis of LUSC.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amlodipine, an L-type Ca2+ channel inhibitor, regulates release of extracellular vesicles from tumor cells.","authors":"Sujan K Mondal, Chang-Sook Hong, Jie Han, Brenda Diergaarde, Dan P Zandberg, Theresa L Whiteside","doi":"10.1093/carcin/bgaf016","DOIUrl":"https://doi.org/10.1093/carcin/bgaf016","url":null,"abstract":"<p><p>Tumor cells produce/release tumor-derived exosomes (TEX) which promote tumor growth, drive immune suppression, and interfere with immune therapies. Amlodipine, a calcium flux inhibitor may block TEX release by tumor cells. Amlodipine's potential as a drug blocking TEX release was evaluated. We measured tumor growth, TEX numbers, phenotype, and molecular content in murine SCCVII and human cancer cell lines. Cell lysates and TEX were tested for expression of autophagy-related proteins by Western blots (WBs). Tumor growth in mice, histopathology, T-cell infiltrations, and TEX production by SCCVII treated with amlodipine were measured. Numbers and protein content of TEX eluted from tumor explants were studied by flow cytometry and WBs. Amlodipine used in vitro at 0.5-5µM was nontoxic, did not impair tumor cell viability, reduced cell proliferation and decreased TEX production. It reduced PD-L1 and Rab11 content of TEX, altered tumor cell size/shape, induced vesicle accumulations in the cytosol and up-regulated expression levels of autophagy-related proteins, ATG7, Beclin-1 and LC3. In vivo, daily treatment of established SCCVII with amlodipine (10mg/kg) inhibited tumor growth (P<0.001), increased CD8+T cell infiltration into tumor, decreased TEX production and altered PD-L1, Rab11 and FasL content of TEX. Amlodipine delivered in vitro to tumor cells or in vivo to tumor-bearing mice interferes with tumor growth and TEX production, induces tumor autophagy, reduces circulating TEX numbers, and alters the TEX immunosuppressive signature. Amlodipine emerges as a potentially promising drug for removing immunosuppressive TEX in cancer subjects who are candidates for immune therapies.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Influence of Homologous Recombination Repair on Temozolomide Chemosensitivity in Gliomas.","authors":"Biyun Zeng, Hansen Shi, Tiancai Liu, Jinjing Tang, Juncheng Lin, Xiaocong Lin, Tao Zeng","doi":"10.1093/carcin/bgaf017","DOIUrl":"https://doi.org/10.1093/carcin/bgaf017","url":null,"abstract":"<p><p>Gliomas represent a prevalent form of primary brain tumors, with temozolomide (TMZ) serving as the established first-line therapeutic option. Nevertheless, the effectiveness of TMZ is hindered by the development of chemoresistance. Recent investigations have underscored the correlation of homologous recombination repair (HRR), a pivotal mechanism responsible for mending DNA double-strand breaks, with TMZ resistance in glioma treatment. This review centers on elucidating the significance of HRR in the management of gliomas, with a particular emphasis on pivotal molecules implicated in the HRR process, including RAD51, ATM, ATR, and newly identified small molecules that impact HRR. Modulating the expression of these genes can effectively restrain pathways such as ATM/CHK2, ATR/CHK1, and PI3K/AKT, subsequently augmenting the sensitivity of gliomas to TMZ. Noteworthy efforts have been directed towards exploring inhibitors of these pathways in recent research endeavors, culminating in encouraging outcomes. In conclusion, the involvement of HRR in glioma resistance unveils novel therapeutic avenues, with targeting crucial molecules in the HRR pathway, holding promise for enhancing the effectiveness of TMZ therapy.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MACC1 is a Potential Prognostic Biomarker for Cancer Immunotherapy in Lung Adenocarcinoma.","authors":"Changqie Pan, Zhiyuan Zhou, Jun Cao, Lemeng Zhang, Tianli Cheng, Haitao Li, Zhou Jiang, Danhui Huang, Dongqiang Zeng, Yongzhong Luo, Jianhua Wu","doi":"10.1093/carcin/bgaf015","DOIUrl":"https://doi.org/10.1093/carcin/bgaf015","url":null,"abstract":"<p><p>Our team previously reported that MACC1 levels are closely related to a variety of tumors and the efficacy of immune checkpoint blockade (ICB) therapy. However, the predictive value of MACC1 levels for lung adenocarcinoma (LUAD) immunotherapy has not been studied. This study aimed to investigate the predictive effect of the oncogene MACC1 on ICB reactivity in patients with LUAD. First, the expression patterns and clinical features of MACC1 in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were comprehensively evaluated using R packages. We subsequently assessed the correlations between MACC1 and immunological characteristics in the LUAD tumor microenvironment (TME) using the CIBERSORT algorithm. The results revealed that MACC1 overexpression was significantly correlated with 3 immune checkpoints, 14 tumor-infiltrating immune cells (TIICs), 9 immunomodulators, 5 anticancer immune process activities and 3 effector genes of TIICs in LUAD. Additionally, on the basis of the prognostic genes from LASSO analysis, we developed the MACC1-related Risk Score (MRRS), which can accurately predict the prognosis and response to cancer immunotherapy in LUAD patients (HR=3.50, AUC at 1, 2, and 3 years = 0.737, 0.744, and 0.724, respectively). Finally, in vivo experiments revealed that the combination of MACC1 silencing and PD-L1 inhibitors significantly inhibit tumor progression. These findings increase our understanding of MACC1 as a potential prognostic biomarker and potential therapeutic target for cancer immunotherapy. The MRRS may play a critical role in predicting the response of LUAD patients to ICB therapy.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted role of transgelin isoforms in cancer hallmarks.","authors":"Ana Maria Jimenez Jimenez, Yazan Haddad, Vendula Jemelikova, Vojtech Adam, Miguel Angel Merlos Rodrigo","doi":"10.1093/carcin/bgaf014","DOIUrl":"https://doi.org/10.1093/carcin/bgaf014","url":null,"abstract":"<p><p>Transgelins (TAGLNs) are actin-binding proteins within the calponin family, playing a crucial role in modulating actin-myosin interactions and maintaining actin filament stability. These proteins are expressed in both smooth and non-smooth muscle cells, contributing to the regulation of muscle contractility and cell migration. TAGLNs family has three isoforms that differ in their isoelectric point, namely: TAGLN1, TAGLN2, and TAGLN3. TAGLNs regulation is involved in the development of many diseases, such as pulmonary arterial hypertension, asthma, atherosclerosis, obstructive nephropathy, diabetes, and cancer. Recent research indicates TAGLNs involvement in carcinogenesis and chemoresistance. This review investigates TAGLNs as potential cancer biomarkers, exploring their versatile tissue-specific impact on patient outcomes. We also highlight their roles as, tumor suppressor agents and tumor progression oncogenes depending on the tumor type, tumor genetic variations and TAGLNs expression profiles. Furthermore, emerging evidence suggests that the interplay between TAGLN2 and chemoresistance to anticancer drugs is mediated by its interaction with the chemoresistance double agent MT-2, with possible bidirectional implications. TAGLNs present a promising avenue for novel therapeutic strategies against cancer, owing to their tissue-specific duality in promoting/suppressing tumor growth and cell migration in cancer cells. Thus, they can serve as a potential prognostic/diagnostic biomarker. The focus should be on leveraging, in future therapeutics, the interplay between TAGLNs and MTs to reverse tumor progression and chemoresistance, transforming them into tumor suppression.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemoresistance and Immune Evasion in HCC: The Role of miRNA-425-5p.","authors":"Xinghe Pan, Junliang Liu, Yitong Zhang, Chenglin Sun, You Li","doi":"10.1093/carcin/bgaf012","DOIUrl":"https://doi.org/10.1093/carcin/bgaf012","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) represents a significant global health challenge, with chemoresistance severely limiting treatment efficacy. This study investigates the role of miRNA-425-5p in exosomes in modulating the tumor microenvironment (TME) and contributing to chemoresistance and immune evasion in HCC. Differentially expressed miRNAs were identified using TaqMan low-density array technology in serum samples from XELOX-resistant and -sensitive HCC patients. miRNA-425-5p expression was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Exosomes from HCC cell lines were characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Functional assays, including luciferase reporter assays and flow cytometry, elucidated the mechanisms of miRNA-425-5p. In vivo studies with mouse xenograft models evaluated the impact of miRNA-425-5p on tumor growth and chemosensitivity. miRNA-425-5p was significantly upregulated in the serum of XELOX-resistant HCC patients and correlated with poorer survival outcomes. Exosomes from chemoresistant HCC cells exhibited increased levels of miRNA-425-5p, which, when internalized by CD4+ T cells, promoted regulatory T cell (Treg) expansion by targeting PTEN. In vivo, miRNA-425-5p overexpression enhanced tumor growth and chemoresistance, while its inhibition reduced tumor size and increased chemosensitivity. These findings indicate that miRNA-425-5p in exosomes plays a crucial role in HCC chemoresistance and immune evasion by modulating the TME and promoting Treg expansion through PTEN targeting. miRNA-425-5p serves as a potential biomarker for predicting chemoresistance and a therapeutic target for overcoming drug resistance in HCC.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manuscript Smoking Behavior-related Genetic Variants and Lung Cancer Risk in Japanese: an Assessment by Mediation Analysis.","authors":"Sayaka Yamamoto, Yuriko N Koyanagi, Yuji Iwashita, Tomohiro Shinozaki, Yutaka Fujiwara, Noriaki Sakakura, Megumi Hara, Yuichiro Nishida, Jun Otonari, Hiroaki Ikezaki, Shiroh Tanoue, Chihaya Koriyama, Yumiko Kasugai, Isao Oze, Teruhide Koyama, Satomi Tomida, Nobuaki Michihata, Yohko Nakamura, Sadao Suzuki, Hiroko Nakagawa-Senda, Mako Nagayoshi, Yoko Kubo, Yasufumi Kato, Kenji Wakai, Takeshi Watanabe, Masashi Ishizu, Naoyuki Takashima, Aya Kadota, Yukihide Momozawa, Masahiro Nakatochi, Takashi Tamura, Akio Niimi, Hidemi Ito, Keitaro Matsuo","doi":"10.1093/carcin/bgaf011","DOIUrl":"https://doi.org/10.1093/carcin/bgaf011","url":null,"abstract":"<p><p>Cigarette smoking is one of the most important risk factors for lung cancer. Genetic studies have shown that smoking behavior-related genetic variants are directly associated with lung cancer, independent of smoking behavior, mainly in European populations. A recent genome-wide association study in Japan identified five loci associated with the number of cigarettes smoked per day. This study aimed to evaluate whether these loci are associated with lung cancer risk directly or indirectly through changing smoking behavior. Here, we conducted a case-control study (1427 cases and 5595 controls) and a prospective cohort study (128 incident cases in 10 520 subjects). Using mediation analysis, we decomposed the total effect of the lead single nucleotide polymorphism (SNP) at each locus on lung cancer risk into direct and indirect effects. The results of the two studies were pooled using a random-effects model to estimate summary relative risks (RRs) and their 95% confidence intervals (CIs). Two studies showed that: (a) rs78277894 (EPHX2-CLU, G>A) had a protective direct effect (RR 0.84; 95% CI 0.77-0.93) on lung cancer risk; and (b) rs56129017 (CYP2A6, C>T) had carcinogenic direct and indirect effects on lung cancer risk (RR 1.26; 95% CI 1.15-1.39 and RR 1.01; 95% CI 1.00-1.01, respectively). This mediation analysis revealed that two smoking behavior-related SNPs, EPHX2-CLU rs78277894 and CYP2A6 rs56129017, were associated with lung cancer risk through pathways independent of changing smoking behavior. Our findings may contribute to our understanding of lung carcinogenesis pathways that cannot be addressed by changes in smoking behavior.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olfactomedin 4 promotes gastric cancer cell G2/M progression and serves as a therapeutic target in gastric adenocarcinoma.","authors":"Wenli Liu, Hongzhen Li, Istvan Botos, Chutima Kumkhaek, Jianqiong Zhu, Griffin P Rodgers","doi":"10.1093/carcin/bgaf010","DOIUrl":"10.1093/carcin/bgaf010","url":null,"abstract":"<p><p>Olfactomedin 4 (OLFM4) is a member of the olfactomedin domain-containing olfactomedin glycoprotein family and plays important roles in innate immunity, inflammation, and cancer. It exhibits increased expression in gastric cancer patient tissues and has been shown to regulate proliferation and apoptosis in gastric cancer cells. However, the molecular mechanism(s) underlying OLFM4's role in gastric cancer remain unknown. In this study, we found that OLFM4 knock-down significantly inhibited YCC3 gastric cancer cell proliferation and induced G2/M cell cycle arrest. Yeast two-hybridization screening revealed that OLFM4 directly interacts with cyclin B1 interacting protein 1 (CCNB1IP1), an E3 ubiquitin protein ligase. In YCC3 cells, OLFM4 co-immunoprecipitated and colocalized with CCNB1IP1, and underwent cell cycle phase-specific nucleo-cytoplasmic shuttling. OLFM4 knockdown decreased both cyclin B1 protein levels and CDK1 activity in YCC3 cells. Screening of a cohort of OLFM4-targeted microRNAs (miRNAs) for their impact on cell proliferation identified several that significantly downregulated OLFM4 protein levels and inhibited YCC3 cell proliferation in vitro. Rescue experiments demonstrated that these miRNAs' inhibitory effect on cell proliferation was partially related to their downregulation of OLFM4. When three of these miRNAs were individually administered intratumorally to nude mice bearing YCC3 cell xenografts, tumor growth was significantly inhibited when compared with tumors treated with a negative control miRNA. These results suggest that OLFM4 promotes cell cycle progression and cell proliferation in gastric cancer cells and may have utility as a therapeutic target in gastric adenocarcinoma.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA MEG3 Suppresses Prostate Cancer Progression by Mediating Macrophage Polarization via the miR-148a-3p/ARRDC3 Signaling Axis.","authors":"Jinguang Luo, Huaixiang Tao, Long Chen, Hao Hu, Likai Mao, Han Guan","doi":"10.1093/carcin/bgaf009","DOIUrl":"https://doi.org/10.1093/carcin/bgaf009","url":null,"abstract":"<p><p>Long-chain non-coding RNA (LncRNA) MEG3 significantly influences tumor microenvironment (TME) dynamics and macrophage polarization. However, its specific involvement in prostate cancer (PCa) progression remains unclear. MEG3 exhibited low expression in PCa, and immune infiltration analysis revealed a positive association with M1 macrophages infiltration and a negative association with M2 macrophages infiltration. Immunohistochemical analysis demonstrated increased MEG3 levels, corresponding with upregulated INOS (an M1 marker) and downregulated CD163 (an M2 marker). MEG3 expression was markedly elevated in LPS-induced M1 macrophages and notably reduced in IL-4-induced M2 macrophages. The overexpression of MEG3 significantly enhanced M1 macrophages polarization while suppressing M2 macrophages polarization. Using an online database and a dual luciferase reporter assay, miR-148a-3p was identified as a downstream target of MEG3. Reduced miR-148a-3p expression was observed in LPS-induced M1 macrophages, while an increase was noted in IL-4-induced M2 macrophages. Moreover, MEG3 overexpression's impact on macrophage polarization was nullified following miR-148a-3p mimic transfection. ARRDC3 was validated as a downstream target of miR-148a-3p. The upregulation of ARRDC3 triggered by MEG3 overexpression was effectively suppressed by miR-148a-3p mimics. Additionally, Knockdown of ARRDC3 effectively counteracted the MEG3 overexpression-induced increase in M1 macrophages polarization while simultaneously mitigating the reduction in M2 macrophages polarization. Collectively, MEG3 exhibits reduced expression in PCa and correlates with macrophage infiltration and polarization. Specifically, it drives M1 macrophages polarization while suppressing M2 macrophages polarization via the miR-148a-3p/ARRDC3 axis, thereby impeding tumor immune evasion and restricting PCa progression.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}