Molecular Carcinogenesis最新文献_第9页

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

SOAT1 Activates NLRP3 Inflammasome to Promote Cancer-Related Lymphangiogenesis and Metastasis via IL-1β/IL-1R-1 Axis in Oral Squamous Cell Carcinoma. SOAT1激活NLRP3炎性体，通过IL-1β/IL-1R-1轴促进口腔鳞状细胞癌相关淋巴管生成和转移

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1002/mc.23907

Chengzhi Zhao, Yuhao Wang, Zhishen Jiang, Shengzhao Guo, Liru Hu, Jian Pan, Fan Dan

{"title":"SOAT1 Activates NLRP3 Inflammasome to Promote Cancer-Related Lymphangiogenesis and Metastasis via IL-1β/IL-1R-1 Axis in Oral Squamous Cell Carcinoma.","authors":"Chengzhi Zhao, Yuhao Wang, Zhishen Jiang, Shengzhao Guo, Liru Hu, Jian Pan, Fan Dan","doi":"10.1002/mc.23907","DOIUrl":"10.1002/mc.23907","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer in the head and neck region, significantly impacting patient survival rates and quality of life. Lymph node (LN) metastasis is a lead contributor to the poor prognosis associated with OSCC. SOAT1 plays a critical role in cholesterol metabolism and has been implicated in various cancers, although its specific mechanisms in OSCC are poorly understood. Additionally, NLRP3 inflammasome has been identified as a factor that promotes cancer progression by influencing various processes involved in tumor development, with its activation linked to cancer metastasis. Lymphangiogenesis enhancing cancer metastasis has been identified in OSCC, while the molecule networks of regulating it remains unclear. In our study, we found that SOAT1 is overexpressed in OSCC and promotes proliferation, migration, and invasion of OSCC cells. Knockdown SOAT1 expression impaired OSCC progression both in vitro and in vivo, and reduced the rate of LN metastasis. RNA sequencing analysis revealed that NLRP3 is a downstream regulated by SOAT1, with NLRP3 inflammasome reactivation having recovered cancer malignancy inhibited by SOAT1 knockdown. Furthermore, we revealed that IL-1β, released by NLRP3 inflammasome activation, could directly bind to IL-1R-1 in lymphatic endothelial cells (LECs), and enhance tube formation capacity of LECs, indicating the potential role of NLRP3 inflammasome in promoting lymphangiogenesis and metastasis in OSCC. In conclusion, SOAT1 could promote OSCC malignancy and regulate the activation of NLRP3 inflammasome to increase the rate of lymphangiogenesis and cancer metastasis via IL-1β/IL-1R-1 axis in OSCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1039-1056"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710802","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

Hsa_circ_0000231 Accelerates Cell Autophagy and Promotes Cell Proliferation and Invasion of Colorectal Cancer via miR-140-3p/Bcl-2 Axis. Hsa_circ_0000231通过miR-140-3p/Bcl-2轴加速细胞自噬，促进结直肠癌细胞增殖和侵袭。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1002/mc.23906

Long Zhao, Haoran Zhang, Shuo Wang, Yushi Zhou, Kewei Jiang, Shan Wang, Yingjiang Ye, Bo Wang, Zhanlong Shen

{"title":"Hsa_circ_0000231 Accelerates Cell Autophagy and Promotes Cell Proliferation and Invasion of Colorectal Cancer via miR-140-3p/Bcl-2 Axis.","authors":"Long Zhao, Haoran Zhang, Shuo Wang, Yushi Zhou, Kewei Jiang, Shan Wang, Yingjiang Ye, Bo Wang, Zhanlong Shen","doi":"10.1002/mc.23906","DOIUrl":"10.1002/mc.23906","url":null,"abstract":"Accumulating evidence indicated that circular RNAs (circRNAs) directly sponge to microRNAs (miRNAs),(miRNAs), which in turn regulate the gene expression and affect the malignancy behavior at the posttranscriptional level. However, the expression levels, function, and mechanism of circ_0000231 in colorectal cancer (CRC) are largely unknown. The expression levels of circ_0000231, miR-140-3p, and Bcl-2 in 110 CRC tissues and matched normal colorectal tissues were detected by qRT-PCR method. circ_0000231 and Bcl-2 were suppressed by siRNA, and miR-140-3p was overexpressed by RNA mimics in CRC cell lines. The function-based experiments were conducted to detect the proliferation and migratory abilities in CRC cell lines. RNA pull-down, RNA immunoprecipitation (RIP), and dual-fluorescence reporter assay were conducted to verify the association among circ_0000231, miR-140-3p, and Bcl-2. Western blot analysis and mRFP-GFP-LC3 adenovirus were used to detect the autophagy level affected by circ_0000231, miR-140-3p, and Bcl-2 axis. Downregulated circ_0000231 significantly suppressed the proliferation and migratory abilities of CRC cells by suppressing autophagy and promoting G0/G1 phase arrest. Furthermore, RNA pull-down, RIP, and dual-fluorescence reporter assays confirmed that circ_0000231 regulates the expression of Bcl-2 by directly targeting miR-140-3p. More importantly, circ_0000231 promoted the levels of autophagy via the miR-140-3p/Bcl-2 axis in CRC. Our study demonstrated that circ_0000231, as a tumor promotor, enhances the level of autophagy by regulating Bcl-2 via targeting miR-140-3p. Moreover, circ_0000231 might serve as a diagnostic and prognostic indicator and a novel molecular target for CRC therapy.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1025-1038"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710799","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

GPR87 Promotes Angiogenesis in Esophageal Squamous Cell Carcinoma via VEGFA Regulation. GPR87通过VEGFA调控促进食管鳞状细胞癌血管生成。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1002/mc.23909

Dengyan Zhu, Donglei Liu, Kai Wu, Xingdong Cheng, Yang Yang

{"title":"GPR87 Promotes Angiogenesis in Esophageal Squamous Cell Carcinoma via VEGFA Regulation.","authors":"Dengyan Zhu, Donglei Liu, Kai Wu, Xingdong Cheng, Yang Yang","doi":"10.1002/mc.23909","DOIUrl":"10.1002/mc.23909","url":null,"abstract":"The role and underlying mechanisms of G protein-coupled receptor 87 (GPR87) in esophageal squamous cell carcinoma (ESCC) remain unclear, despite its established oncogenic functions in other malignancies. This study examined the expression of GPR87 and its association with survival rate in ESCC using online databases. The expression of GPR87 in ESCC tissues was identified using immunohistochemistry, and a correlation analysis was carried out using ki-67 data. ESCC cells were transfected with GPR87 knockdown or overexpression plasmids, followed by functional assays such as, CCK-8 for cell viability, colony formation for proliferation, wound healing for migration, Transwell for invasion, and tube formation for angiogenesis. Western blot analysis was used to assess STAT3 phosphorylation and VEGFA expression. Additionally, a xenograft tumor model was established to investigate the effect of GPR87 on tumor growth in vivo. The findings demonstrated that GPR87 was highly expressed in ESCC tissues and its overexpression was associated with a poor patient survival. Transfection with a GPR87 overexpression plasmid increases the cell viability, invasion, proliferation, and angiogenesis of ESCC cells, while transfection with sh-GPR87 reversed these effects. Additionally, GPR87 controlled VEGFA expression levels by promoting STAT3 phosphorylation. Rescue trials further verified that GPR87 promotes the growth of ESCC by modulating STAT3. Moreover, in vivo studies validated that GPR87 knockdown suppressed tumor growth. In conclusion, the findings highlight GPR87 as a key regulator of VEGFA expression via STAT3 activation, contributing to ESCC malignancy. Targeting GPR87 may provide a potential therapeutic strategy for ESCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1057-1065"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710796","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

Expression of Concern: Alterations of RASSF1A in Premalignant Cervical Lesions: Clinical and Prognostic Significance. 关注表达：宫颈癌前病变中RASSF1A的改变：临床和预后意义。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-01 Epub Date: 2025-01-27 DOI: 10.1002/mc.23888

引用次数: 0

ARMC10 Drives Glioblastoma Progression Through Activating Notch Pathway. ARMC10通过激活Notch通路驱动胶质母细胞瘤进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-01 Epub Date: 2025-02-23 DOI: 10.1002/mc.23895

Bin Feng, Taihong Gao, Lin Chen, Yi Xing

{"title":"ARMC10 Drives Glioblastoma Progression Through Activating Notch Pathway.","authors":"Bin Feng, Taihong Gao, Lin Chen, Yi Xing","doi":"10.1002/mc.23895","DOIUrl":"10.1002/mc.23895","url":null,"abstract":"This study aimed to check the biological functions and uncover the mechanism of armadillo repeat protein C10 (ARMC10) in glioblastoma (GBM). The expression and potential mechanisms of ARMC10 in GBM were analyzed by bioinformatics analysis. In GBM cells, function-loss experiments were used to evaluate the influences of ARMC10 on cell proliferation, cell invasion, lipid levels, and cell migration by colony formation assay, 5-ethynyl-2'-deoxyuridine staining, cell counting kit-8 assay, transwell assay, BODIPY staining, and wound healing assay. Mouse xenograft models were constructed to validate the influences of ARMC10 in vivo. ARMC10 levels in GBM were upregulated, and patients with low ARMC10 levels displayed a better prognosis. ARMC10 knockdown resulted in a decrease of GBM cell invasion, migration, and proliferation. GSEA showed that ARMC10 was positively associated with the Notch pathway and fatty acid metabolism. ARMC10 knockdown reduced the levels of triglyceride, cholesterol, and lipid, and inhibited the expression of proteins related to fatty acid metabolism and Notch pathway. Moreover, notch receptor 1 (Notch1) overexpression reversed the inhibition of cell proliferation, fatty acid metabolism, and invasion induced by ARMC10 knockdown. In vivo, ARMC10 knockdown suppressed tumor growth. RMC10 knockdown suppressed GBM malignant progression, which had a bearing on Notch pathway.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"883-896"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483699","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

Potential Crosstalk Between ANXA1+ Epithelial Cells and FABP4+ TAM Cells of Ferroptosis-Related Molecular Clusters Promotes an Immunosuppressive Microenvironment in Non-Small Cell Lung Cancer. 凋亡相关分子簇ANXA1+上皮细胞和FABP4+ TAM细胞之间的潜在串扰促进了非小细胞肺癌的免疫抑制微环境

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-01 Epub Date: 2025-03-04 DOI: 10.1002/mc.23899

Shengqiang Mao, Qingyan Li, Ying Yang, Zhiqiang Liu, Li Zhang

{"title":"Potential Crosstalk Between ANXA1+ Epithelial Cells and FABP4+ TAM Cells of Ferroptosis-Related Molecular Clusters Promotes an Immunosuppressive Microenvironment in Non-Small Cell Lung Cancer.","authors":"Shengqiang Mao, Qingyan Li, Ying Yang, Zhiqiang Liu, Li Zhang","doi":"10.1002/mc.23899","DOIUrl":"10.1002/mc.23899","url":null,"abstract":"The tumor microenvironment (TME) affects tumor initiation, invasion, metastasis, and therapies. Recently, increasing evidence has demonstrated that ferroptosis plays important regulatory roles in tumourigenesis and progression. It is unclear how ferroptosis affects non-small cell lung cancer (NSCLC) progression by remodeling the TME. In this study, the single-cell RNA sequencing (scRNA-seq) data (85,562 cells, n = 18) were employed to reveal the heterogeneity of ferroptosis activation in NSCLC, and identified six ferroptosis-related molecular clusters. We found that ANXA1+ epithelial and FABP4 + TAM subpopulations were key factors in lung cancer progression and TME remodeling. In addition, the cell-cell communication analysis showed that ANXA1-FPR2/FPR1 receptor-ligand pair contributed to the formation of an immunosuppressive TME. Furthermore, we established a novel signature based on ferroptosis-related molecular clusters, and the risk score model may predict survival and response to immunotherapy. We also found that compared with responder, the expression of ANXA1 and FABP4 is higher in progressor, which indicating a higher expression of ANXA1 and FABP4 was associated with a worse response to immunotherapy. Therefore, we concluded that the molecular clusters associated with ferroptosis served as potential prognostic markers and therapeutic targets for NSCLC patients.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"936-950"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557486","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

SPP1 Promotes NSCLC Brain Metastasis Via Sequestration of Ubiquitin Ligase RNF114 to Facilitate P85α Ubiquitination. SPP1通过隔离泛素连接酶RNF114促进P85α泛素化，促进NSCLC脑转移。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-01 Epub Date: 2025-02-07 DOI: 10.1002/mc.23866

Xiaoqin Li, Yun Wu, Baosong Xie, Mingxiao Xu, Tianjian Xie, Wenxiang Yue, Ming Lin, Ying Lin, Yusheng Chen

{"title":"SPP1 Promotes NSCLC Brain Metastasis Via Sequestration of Ubiquitin Ligase RNF114 to Facilitate P85α Ubiquitination.","authors":"Xiaoqin Li, Yun Wu, Baosong Xie, Mingxiao Xu, Tianjian Xie, Wenxiang Yue, Ming Lin, Ying Lin, Yusheng Chen","doi":"10.1002/mc.23866","DOIUrl":"10.1002/mc.23866","url":null,"abstract":"Brain metastasis (BM) is a significant factor contributing to the poor prognosis of patients with non-small cell lung cancer (NSCLC). Secreted phosphoprotein 1 (SPP1) is implicated in the progression and metastasis of several cancers. The role of SPP1 in NSCLC remains unclear, especially in NSCLC BM. This study aimed to identify genes associated with NSCLC BM and to investigate the involvement of SPP1 in NSCLC BM. Integrated genomic analysis was utilized to identify candidate genes in NSCLC. The expression levels of SPP1 were evaluated in NSCLC tissues and cell lines. In vitro and in vivo experiments were conducted to assess the effect of SPP1 on NSCLC cell behavior and BM. The potential mechanisms of SPP1 were demonstrated by CO-IP and liquid chromatography-mass spectrometry (LC-MS). The underlying mechanism involving the PI3K/AKT/mTOR pathway was explored. The results showed that SPP1 expression was upregulated in NSCLC tissues and cell lines. Depletion of SPP1 using shRNA inhibited cell proliferation, migration, and invasion in vitro and suppressed BM in vivo. Mechanistically, SPP1 facilitates the ubiquitination of P85α by interacting with the ubiquitin ligase RNF114, thus playing a role in regulating NSCLC BM through the PI3K/AKT/mTOR signaling pathway. Moreover, immunohistochemistry staining confirmed higher expression of SPP1 in NSCLC tissues with BM compared to those without BM. In summary, elevated SPP1 expression was associated with poor clinical outcomes in NSCLC patients. This study highlights the role of SPP1 as a regulator of cell metastasis and suggests its potential as a novel therapeutic target for BM in NSCLC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"829-841"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365273","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