Molecular Carcinogenesis最新文献

C1QBP Promotes Prostate Cancer Progression and Lipid Accumulation by Negatively Regulating ALDH9A1. C1QBP通过负调控ALDH9A1促进前列腺癌进展和脂质积累。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-18 DOI: 10.1002/mc.23904

Xinyu Liu, Jiaxin Li, Runxuan Du, Qiufang Qiao, Shuang Liu, Zhihao Bo, Ruibing Chen, Yihan Dong, Xuesong Xiao, Yuejing Pan, Huamao Jiang, Rui Wang, Yong Wang, Dan Yue

{"title":"C1QBP Promotes Prostate Cancer Progression and Lipid Accumulation by Negatively Regulating ALDH9A1.","authors":"Xinyu Liu, Jiaxin Li, Runxuan Du, Qiufang Qiao, Shuang Liu, Zhihao Bo, Ruibing Chen, Yihan Dong, Xuesong Xiao, Yuejing Pan, Huamao Jiang, Rui Wang, Yong Wang, Dan Yue","doi":"10.1002/mc.23904","DOIUrl":"10.1002/mc.23904","url":null,"abstract":"Prostate cancer (PCa) relies heavily on lipid metabolism for energy acquisition, and lipid metabolic reprogramming plays a crucial role in its progression. Here, we utilized publicly available PCa databases and immunohistochemistry to evaluate C1QBP expression in PCa. We found that C1QBP is highly expressed in PCa, potentially due to promoter hypomethylation. Functional assays showed that C1QBP promotes cell proliferation, migration, and lipid accumulation in PCa cells. We identified differentially expressed proteins associated with C1QBP by using liquid chromatography-tandem mass spectrometry. Functional enrichment analysis revealed that C1QBP affects lipid metabolism and negatively regulates the lipid metabolism-related molecule ALDH9A1. Furthermore, ALDH9A1 intervention rescued the tumor suppression and lipid reduction caused by C1QBP knockdown. RNA sequencing (RNA-seq) was performed to explore C1QBP regulatory pathways at the mRNA level, revealing that C1QBP also affects the MAPK and p53 pathways, as well as the expression of lipid metabolism-related molecules. In conclusion, these findings suggest that C1QBP influences PCa progression and lipid deposition by regulating ALDH9A1, while other potential mechanisms may also be involved, indicating that C1QBP is a promising target for PCa treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"997-1012"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CtBP2 Regulates Wnt Signal Through EGR1 to Influence the Proliferation and Apoptosis of DLBCL Cells. CtBP2通过EGR1调控Wnt信号影响DLBCL细胞的增殖和凋亡

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-18 DOI: 10.1002/mc.23901

Jianfang Dong, Lihua Li, Xuefei Zhang, Xijing Yin, Zucong Chen

{"title":"CtBP2 Regulates Wnt Signal Through EGR1 to Influence the Proliferation and Apoptosis of DLBCL Cells.","authors":"Jianfang Dong, Lihua Li, Xuefei Zhang, Xijing Yin, Zucong Chen","doi":"10.1002/mc.23901","DOIUrl":"10.1002/mc.23901","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of lymphoma. The overexpression of CtBP2 in tissues may contribute to tumor occurrence and progression. The expression of EGR1 in DLBCL is elevated, suggesting its potential role as an oncogene that promotes the proliferation of DLBCL cells. Database predictions indicate that CtBP2 can bind to EGR1. The objective of the present study was to investigate whether CtBP2 can influence the proliferation and apoptosis of DLBCL cells by regulating the Wnt signaling pathway through EGR1. Western blot assay showed that CtBP2 expression was upregulated in DLBCL cells. Cell proliferation level was detected by CCK8 assay and EdU staining, and the apoptosis level and cycle distribution were analyzed through flow cytometry. Our data indicated that interference with CtBP2 and EGR1 can inhibit the proliferation and cell cycle progression of DLBCL cells while promoting apoptosis. The predictions from the HDOCK server, along with the results of Co-IP experiments, suggested that EGR1 and CtBP2 can effectively bind to each other, with EGR1 positioned downstream of CtBP2 and regulated by it. Furthermore, interference with CtBP2 could also inhibit the expression of the Wnt/β-catenin signaling pathway. Overexpression of EGR1 counteracted the effects of siRNA-CtBP2, promoting cell proliferation and cycle, inhibiting apoptosis and upregulating the expression of the Wnt/β-catenin signaling pathway. From the above experiments, we found that CtBP2 can regulate the Wnt/β-catenin signaling pathway through EGR1 to influence the proliferation and apoptosis of DLBCL cells. Therefore, EGR1 may be one of the key contributors involved in the regulation of Wnt/β-catenin signaling by CtBP2.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"959-969"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TSPAN31 Activates Fatty Acid Metabolism and PI3K/AKT Pathway to Promote Tumor Progression in Breast Cancer. TSPAN31激活脂肪酸代谢和PI3K/AKT通路促进乳腺癌肿瘤进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1002/mc.23912

Wenquan Luo, Yuxiang Sun, Liang Cao

{"title":"TSPAN31 Activates Fatty Acid Metabolism and PI3K/AKT Pathway to Promote Tumor Progression in Breast Cancer.","authors":"Wenquan Luo, Yuxiang Sun, Liang Cao","doi":"10.1002/mc.23912","DOIUrl":"10.1002/mc.23912","url":null,"abstract":"Breast cancer (BC) is one of the most common human malignancies, but the mechanisms of BC have not been fully elucidated. Recently, tetraspanin 31 (TSPAN31) is reported to be linked to cancer progression. However, the function of TSPAN31 remains unclear in BC. Investigation of the function and potential mechanism of TSPAN31 in BC was the purpose of this study. Immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were applied to measure TSPAN31 expression. Loss and gain functional experiments were utilized to survey the influences of TSPAN31 on BC biological process, including cell growth, invasion, migration, and fatty acid metabolism. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis based on DepMap database and Gene Set Enrichment Analysis based on The Cancer Genome Atlas database were executed to find TSPAN31-related pathway. Western blot was carried out to assess the changes of fatty acid synthase (FASN), sterol regulatory element binding protein 1 (SREBP1), acyl-CoA synthetase long-chain family member 1 (ACSL1), phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-PI3K, protein kinase B (AKT), and p-AKT. In human non-triple negative breast cancer tissues and cells, TSPAN31 expression was upregulated. TSPAN31 knockdown induced BC cell apoptosis, inhibited cell proliferation, invasion, migration, and fatty acid metabolism, and reduced the protein levels of FASN, SREBP1, ACSL1, p-PI3K/PI3K, and p-AKT/AKT. In contrast, TSPAN31 overexpression led to the opposite results. Additionally, the activator of PI3K (740 Y-P) attenuated the inhibition of TSPAN31 knockdown on fatty acid metabolism, proliferation, and invasion in BC cells. Through activation of fatty acid metabolism and PI3K/AKT pathway, TSPAN31 played a carcinogenic role in BC. For the mechanism of BC tumorigenesis, our study provides an interesting insight.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1078-1089"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of SIRT6 Expression With Risk of Pneumonitis Induced by Radiotherapy in Cancer Patients. SIRT6表达与癌症患者放疗所致肺炎风险的关系

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1002/mc.23900

Fengyuan Yu, Zheng Gong, Yuan Li, Danial F Naseem, Chen Li, Miaowei Wen, Bingying Zhao, Zhezhe Xu, Shanshan Zhang, Rukun Zang, Ailu Wu, Qingxin Han, Shuhui Wu, Hongwei Li, Yipeng Song

{"title":"Association of SIRT6 Expression With Risk of Pneumonitis Induced by Radiotherapy in Cancer Patients.","authors":"Fengyuan Yu, Zheng Gong, Yuan Li, Danial F Naseem, Chen Li, Miaowei Wen, Bingying Zhao, Zhezhe Xu, Shanshan Zhang, Rukun Zang, Ailu Wu, Qingxin Han, Shuhui Wu, Hongwei Li, Yipeng Song","doi":"10.1002/mc.23900","DOIUrl":"10.1002/mc.23900","url":null,"abstract":"Thoracic tumours represent a significant proportion of malignant cancers. While radiotherapy (RT) improves prognosis, it can also lead to side effects such as radiation-induced pneumonitis (RP). Since SIRT6 is involved in DNA repair, energy metabolism and inflammation, this study aims to investigate the expression of SIRT6 in lymphocytes as a potential biomarker and therapeutic target for RP. This study included 170 patients diagnosed with thoracic tumours, all of whom underwent thoracic RT. RP was evaluated and classified as severe RP (SRP) and lower as non-severe RP (NSRP). Analyses were performed using SPSS version 26.0 and the R. Among 170 patients in this study, 124 developed NSRP, and 46 experienced SRP. The univariate analysis showed that SIRT6 expression (cOR, 0.33, 95%CI, 0.18-0.97 before RT and 0.31, 0.19-0.98 after RT), clinical factors, dosimetric parameters and haematological/serological parameters were associated with SRP before and after RT. Our multivariable logistic regression showed that SIRT6 expression was significantly associated with risk of SRP before (aOR, 0.32, 95%CI, 0.15-0.96) and after RT (aOR, 0.32, 95%CI, 0.18-0.99) after adjustment with other confounders. Moreover, the receiver operating characteristic curve analysis revealed that the combined multivariable model exhibited superior predictive capability compared to any single predictor (overall AUC, 0.93, 95%CI, 0.90-0.97 before RT and AUC, 0.91, 95%CI, 0.87-0.96 after RT). The expression of SIRT6 alone or in combination with other risk factors was associated with an increased risk of SRP, suggesting a novel approach for the prevention and treatment of radiation pneumonitis in clinical practice.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1104-1118"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

P21-Activated Kinase 1 (PAK1) Modulates Therapeutic Response to Ionizing Radiation in Head and Neck Squamous Cell Carcinoma Cells. p21活化激酶1 （PAK1）调节头颈部鳞状细胞癌细胞对电离辐射的治疗反应。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-18 DOI: 10.1002/mc.23902

Swetha Rajendran, Rohan Prasad Surabhi, A Satheesh Kumar, Prarthana Gopinath, Vishnupriya Kanakaveti, Gouthaman Shanmugasundaram, M Michael Gromiha, Suresh Kumar Rayala, Ganesh Venkatraman

{"title":"P21-Activated Kinase 1 (PAK1) Modulates Therapeutic Response to Ionizing Radiation in Head and Neck Squamous Cell Carcinoma Cells.","authors":"Swetha Rajendran, Rohan Prasad Surabhi, A Satheesh Kumar, Prarthana Gopinath, Vishnupriya Kanakaveti, Gouthaman Shanmugasundaram, M Michael Gromiha, Suresh Kumar Rayala, Ganesh Venkatraman","doi":"10.1002/mc.23902","DOIUrl":"10.1002/mc.23902","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) continues to be a formidable epithelial malignancy characterized by late-stage detection and recurrence impacting survival. P21-activated kinase-1 (PAK1) was reported to be overexpressed in head and neck cancers and activated by ionizing radiation (IR), affecting treatment outcomes. Present investigations revealed that PAK1 silencing on HNSCC cells reverted the aggressive phenotype and showed impaired DNA damage repair upon IR exposure. Further HNSCC cells were resistant to IR up to 30 Gy with elevated pPAK1 levels. Radiation-resistant (RR) HNSCC cells expressed radiation-resistant markers, namely MRE-11 and NME-1; stemness markers-OCT4 and SOX2; and EMT & metastasis markers-vimentin, snail, and α-smooth muscle actin (α-SMA). In addition, HNSCC RR cells showed increased levels of DNA damage response protein H2AX, indicative of an aggressive phenotype with an augmented DNA repair machinery and a potential target for inhibition. Since H2AX appears to be a mechanistic hub for PAK1-induced radiation resistance, using in silico methods, peptides were designed, and the PL-8 peptide was chosen to target the phosphorylation of H2AX, which could enhance the sensitivity to IR and push the cells to radiation-induced cell death. PL-8 peptide inhibited H2AX phosphorylation on HNSCC cells and triggered radiation-induced cell death as determined by functional assays. The present study reveals PAK1 induced in HNSCC cells by IR and causes resistance by enhancing DNA damage response mediated through γH2AX. To counteract this complex molecular interplay, we propose inhibiting γH2AX formation & silencing PAK1 appears to be a probable way forward in HNSCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"970-984"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interferon-Inducible ADAR1 p150 Is Essential for the Survival of Oral Squamous Cell Carcinoma. 干扰素诱导的ADAR1 p150对口腔鳞状细胞癌的生存至关重要。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1002/mc.23910

Pei San Yee, Annie Wai Yeeng Chai, Shi Mun Yee, Shiyin Ooi, Yee Hua Tan, Mathew J Garnett, Siew Kit Ng, Sok Ching Cheong

{"title":"Interferon-Inducible ADAR1 p150 Is Essential for the Survival of Oral Squamous Cell Carcinoma.","authors":"Pei San Yee, Annie Wai Yeeng Chai, Shi Mun Yee, Shiyin Ooi, Yee Hua Tan, Mathew J Garnett, Siew Kit Ng, Sok Ching Cheong","doi":"10.1002/mc.23910","DOIUrl":"10.1002/mc.23910","url":null,"abstract":"We identified ADAR1 as one of the top essential genes for oral squamous cell carcinoma (OSCC) survival from our genome-wide CRISPR/Cas9 screen in OSCC cell lines. In this study, we confirm that ADAR1-knockout (KO) inhibits cell viability and colony forming ability, and induces apoptosis. We report that IFN-β treatment sensitizes less-dependent cell lines to ADAR1 KO-induced cell lethality. Overexpression of ADAR1-p150, but not ADAR1-p110, rescued cell lethality upon ADAR1 KO, confirming that the IFN-inducible p150 is responsible for OSCC survival. Using a deaminase inactive mutant, we demonstrate that the editing function of ADAR1 is important for OSCC survival. Furthermore, we show that ADAR1 KO-induced cell death is mediated by both PKR and MDA5. We compute gene signatures of ADAR1 dependency in OSCC tumors, and found that those with high ADAR1 dependency score are associated with well or moderate differentiation, likely due to high PKR expression or activation. While a majority of ADAR1-dependent tumors exhibit a low T cell-inflamed gene expression profile, ADAR1 KO upregulates PD-L1, a marker of anti-PD1 response, indicating that ADAR1 inhibition may enhance immunotherapy response in OSCC. Collectively, these findings suggest that targeting ADAR1-p150 not only induces OSCC cell death but could induce a favorable response to anti-PD1.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1066-1077"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LINC02154 Promotes Esophageal Squamous Cell Carcinoma Progression via the PI3K-AKT-mTOR Signaling Pathway by Interacting With IGF2BP2. LINC02154通过PI3K-AKT-mTOR信号通路与IGF2BP2相互作用促进食管鳞状细胞癌进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-18 DOI: 10.1002/mc.23903

Mingyuan Zhang, Cai Zhang, Fuyou Zhou, Ruotong Yang, Yang Feng, Yangyang Ji, Huijun Ren, Liang Ming

引用次数: 0

Circ_0044362 Facilitates the Progression of Epithelial Ovarian Cancer via Enhancing HOXB4 Transcription to Activate the RUNX1/IGFBP3 Axis. Circ_0044362通过增强HOXB4转录激活RUNX1/IGFBP3轴促进上皮性卵巢癌的进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-18 DOI: 10.1002/mc.23905

Shengtou Ye, Han Wu, Junjiang Liu, Jianguo Zhou, Sisi He, Na Li

{"title":"Circ_0044362 Facilitates the Progression of Epithelial Ovarian Cancer via Enhancing HOXB4 Transcription to Activate the RUNX1/IGFBP3 Axis.","authors":"Shengtou Ye, Han Wu, Junjiang Liu, Jianguo Zhou, Sisi He, Na Li","doi":"10.1002/mc.23905","DOIUrl":"10.1002/mc.23905","url":null,"abstract":"Increasing numbers of studies have elucidated the emerging roles of circular RNA (circRNA) in cancer progression. However, the function of circRNAs in modulating their parental genes in ovarian cancer remains poorly understood. In this study, we identified that circ_0044362, a circRNA derived from homeobox B4 (HOXB4), significantly promotes the expression of its parental gene HOXB4 in ovarian cancer. Functionally, circ_0044362 promotes the malignant phenotypes of ovarian cancer cells. Further analysis revealed that circ_0044362 facilitates the transcriptional activation of its parental gene HOXB4 by directly guiding U1 small nuclear ribonucleoprotein (snRNP) to its promoter region, thereby enhancing the oncogenic behaviors of ovarian cancer cells. Furthermore, HOXB4 positively regulates runt-related transcription factor 1 (RUNX1) expression, with RUNX1 serving as a transcription factor to promote the transcription of insulin-like growth factor binding protein-3 (IGFBP3). Notably, inhibitors of either HOXB4, RUNX1, or IGFBP3 could reverse the oncogenic activity mediated by circ_0044362. Collectively, our findings reveal the involvement of the circ_0044362/HOXB4 pathway in ovarian cancer progression and provide potential therapeutic strategies for ovarian cancer treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1013-1024"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miR-135b-5p/PDE3B Axis Regulates Gemcitabine Resistance in Pancreatic Cancer Through Epithelial-Mesenchymal Transition. miR-135b-5p/PDE3B轴通过上皮-间质转化调控胰腺癌吉西他滨耐药

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1002/mc.23914

Yuxuan Fu, Liangsheng Chen, Neng Lv, Jia Wang, Shuwei Yu, Qilu Fang, Wenxiu Xin

引用次数: 0

KCNE3 Facilitates M1 Macrophage Polarization by Suppressing the Wnt/β-Catenin Pathway, Inhibiting Glioma Proliferation, Migration, and Invasion. KCNE3通过抑制Wnt/β-Catenin通路，抑制胶质瘤增殖、迁移和侵袭，促进M1巨噬细胞极化。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-27 DOI: 10.1002/mc.23911

Shangyu Liu, Qiao Li, Liang Niu, Peng Feng, Wenshan Li, Ying Dang, Juan Jia, Guoqiang Yuan, Yawen Pan

{"title":"KCNE3 Facilitates M1 Macrophage Polarization by Suppressing the Wnt/β-Catenin Pathway, Inhibiting Glioma Proliferation, Migration, and Invasion.","authors":"Shangyu Liu, Qiao Li, Liang Niu, Peng Feng, Wenshan Li, Ying Dang, Juan Jia, Guoqiang Yuan, Yawen Pan","doi":"10.1002/mc.23911","DOIUrl":"10.1002/mc.23911","url":null,"abstract":"The glioma microenvironment is critical for tumor growth, where reprogramming M2-polarized tumor-associated macrophages/microglia (TAMs) to an antitumor M1 phenotype represents a promising therapeutic strategy. While the potassium channel regulatory subunit KCNE3 has been implicated in tumorigenesis across malignancies, its functional role in shaping the glioma microenvironment remains undefined. Here, we leveraged transcriptome data from the Gene Expression Omnibus (GEO) to identify KCNE3 as a TAM-enriched gene in gliomas. To interrogate its mechanistic contributions, we generated KCNE3-knockdown and overexpressing macrophages and evaluated their impact on glioma cells in coculture systems. Silencing KCNE3 in macrophages significantly attenuated glioma cell proliferation, migration, and invasion in vitro, accompanied by enhanced M1 polarization. Mechanistically, KCNE3 depletion suppressed Wnt/β-catenin signaling, driving increased secretion of pro-inflammatory cytokines TNF-α, IL-6, and IL-12. Conversely, KCNE3 overexpression reversed these effects, promoting M2-like characteristics and tumor-supportive behaviors. These findings establish KCNE3 as a key modulator of TAM phenotype and glioma progression, suggesting that targeted KCNE3 inhibition may disarm pro-tumorigenic immune responses to improve therapeutic outcomes. This study uncovers a novel actionable method in glioma immunotherapy.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1090-1103"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0