Molecular Carcinogenesis最新文献

SRPK1 Activation Facilitates Gli3^S664 Phosphorylation and Promotes Metastasis in Esophageal Squamous Cell Carcinoma. SRPK1激活促进Gli3S664磷酸化并促进食管鳞状细胞癌转移

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-13 DOI: 10.1002/mc.23913

Yongwei Ding, Jiace Qin, Mengjia Zhang, Huiting Wu, Chang Liu, Yaping Guo, Wenjie Wu, Yanan Jiang, Chenjuan Zhang, Yanying Ma, Xinghuan Chen, Jing Lu, Kangdong Liu, Ziming Dong, Jimin Zhao, Yan Qiao

{"title":"SRPK1 Activation Facilitates Gli3S664 Phosphorylation and Promotes Metastasis in Esophageal Squamous Cell Carcinoma.","authors":"Yongwei Ding, Jiace Qin, Mengjia Zhang, Huiting Wu, Chang Liu, Yaping Guo, Wenjie Wu, Yanan Jiang, Chenjuan Zhang, Yanying Ma, Xinghuan Chen, Jing Lu, Kangdong Liu, Ziming Dong, Jimin Zhao, Yan Qiao","doi":"10.1002/mc.23913","DOIUrl":"10.1002/mc.23913","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) stands out as one of the most malignant digestive tumors, with its prognosis marred by frequent metastasis and recurrence. However, the mechanism behind ESCC metastasis remains elusive, impeding therapeutic advancements. SRPK1 emerges as an independent prognostic marker for ESCC patients. Our research illuminates the consequential role of SRPK1, where its genetic knockout led to decreased levels of transcription factors Snail and Slug, concomitant with an enhanced expression of the cell-to-cell adhesion protein E-cadherin. Conversely, reintroducing an overexpression of SRPK1 reversed the effects, highlighting its essential role in ESCC metastasis. Through bioinformatics analysis, we identified a correlation between SRPK1 and Gli3. Furthermore, increased levels of Gli3 and its phosphorylated form, p-Gli3S664, were detected in ESCC tissues, which are implicated in promoting ESCC metastasis. Notably, our research confirmed that SRPK1 promotes migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells through phosphorylates Gli3 at ser 664. Additional investigations reveal that dihydroartemisinin (DHA) effectively impedes ESCC cell metastasis by suppressing SRPK1-mediated phosphorylation of Gli3S664 both in vitro and in vivo. Consequently, our study underscores the pivotal role of the SRPK1-p-Gli3S664 axis in ESCC metastasis and suggests DHA as a promising candidate for preventing ESCC metastasis by targeting this axis.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1168-1181"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008578","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

Correction to "Cucurbitacin B Induces Inhibitory Effects via CIP2A/PP2A/Akt Pathway in Glioblastoma Multiforme". 更正“葫芦素B通过CIP2A/PP2A/Akt通路诱导多形性胶质母细胞瘤的抑制作用”。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-07 DOI: 10.1002/mc.23917

引用次数: 0

ENC1 Promotes the Malignant Progression and Metastasis by Suppressing TRIM21 Mediated Vimentin Degradation in Wilms Tumor. ENC1通过抑制TRIM21介导的维entin降解促进Wilms肿瘤的恶性进展和转移。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-13 DOI: 10.1002/mc.23918

Zhiyi Lu, Hongjie Gao, Fan Huang, Zuohui Zhao, Jiawei Chen, Fengyin Sun

{"title":"ENC1 Promotes the Malignant Progression and Metastasis by Suppressing TRIM21 Mediated Vimentin Degradation in Wilms Tumor.","authors":"Zhiyi Lu, Hongjie Gao, Fan Huang, Zuohui Zhao, Jiawei Chen, Fengyin Sun","doi":"10.1002/mc.23918","DOIUrl":"10.1002/mc.23918","url":null,"abstract":"Ectodermal neural cortex 1 (ENC1) is significantly upregulated in various cancers and shows a positive correlation with poor prognosis and advanced clinical stages, such as colorectal cancer, endometrial cancer and breast cancer. However, the role of ENC1 in Wilms tumor (WT) has not been previously reported. In this study, we conducted several in vitro functional experiments and established xenograft models to confirm the oncogenic potential of ENC1. The binding proteins of ENC1 were identified through co-immunoprecipitation and mass spectrometry to screen the mechanism of malignant progression. Further analysis elucidated the mechanism by which ENC1 promotes tumorigenesis. The results demonstrated that ENC1 was significantly overexpressed in tumor and recurrence samples, with elevated ENC1 expression showing a significant negative correlation with both overall survival and recurrence-free survival of patients. Functionally, the role of ENC1 in tumor oncogenicity was elucidated through the assessment of tumor cell proliferation, migration, and invasion capabilities. Mechanistically, through immunoprecipitation and mass spectrometry, we identified Vimentin as an interacting protein of ENC1. ENC1 competed with the E3 ubiquitin ligase TRIM21 for Vimentin binding, thereby reducing the ubiquitination level of Vimentin and enhancing its protein stability. In conclusion, this study demonstrates that ENC1 functions as a novel oncogenic target for Wilms tumor by disrupting TRIM21-mediated ubiquitination of Vimentin, which presents novel insights for the treatment of Wilms tumor and the development of prognostic markers.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1182-1194"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990591","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

Targeting FGFR Attenuates Tumor Growth in an Anal Squamous Cell Carcinoma Patient Derived Xenograft Model. 靶向FGFR减缓肛门鳞状细胞癌患者衍生异种移植模型的肿瘤生长。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-21 DOI: 10.1002/mc.23919

Thuc Ly, Athena E Golfinos-Owens, Naren Raja, Levi Arnold, Pachiappan Arjunan, John Ashcraft, Benjamin Martin, Shrikant Anant, Sumedha Gunewardena, Rong Wang, Huy Q Dinh, Sufi Mary Thomas

{"title":"Targeting FGFR Attenuates Tumor Growth in an Anal Squamous Cell Carcinoma Patient Derived Xenograft Model.","authors":"Thuc Ly, Athena E Golfinos-Owens, Naren Raja, Levi Arnold, Pachiappan Arjunan, John Ashcraft, Benjamin Martin, Shrikant Anant, Sumedha Gunewardena, Rong Wang, Huy Q Dinh, Sufi Mary Thomas","doi":"10.1002/mc.23919","DOIUrl":"10.1002/mc.23919","url":null,"abstract":"Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence and limited treatment options. To identify actionable therapeutic targets, we developed a patient-derived xenograft (PDX) model using a metastatic ASCC sample and performed single-cell RNA sequencing. Our analysis confirmed previously reported genetic mutations highly expressed in the sample, along with copy number alterations, and revealed epithelial cancer cell heterogeneity. Notably, epithelial cells exhibited a low hybrid epithelial-mesenchymal transition (hEMT) signature compared to stromal cells. Among epithelial subpopulations, the most abundant cluster displayed high expression of FGFR1-2 and FGF ligands. Treatment with AZD4547, an FGFR1-3 inhibitor, resulted in a significant reduction in tumor volume over time (p = 0.0036). Immunohistochemistry staining for proliferative Ki67 and cleaved caspase 3 suggested ongoing proliferation in residual cells. Fourier-transform infrared (FTIR) spectroscopy of post-treatment residual tumors revealed significant differences in the Amide I and Amide II regions between AZD4547-treated and control groups. These findings demonstrate that FGFR inhibition effectively attenuates ASCC tumor growth and highlights the promise of precision medicine in managing this rare cancer.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1236-1246"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019277","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

CYP4F11, an NRF2 Target Gene, Promotes Hepatocellular Carcinoma Cell Growth. NRF2靶基因CYP4F11促进肝癌细胞生长

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-05-06 DOI: 10.1002/mc.23925

Jinjing Chen, Carlee A Trindl, Haofeng Ye, Dichun Huang, Aikseng Ooi, Joe G N Garcia, Eli Chapman, Donna D Zhang

{"title":"CYP4F11, an NRF2 Target Gene, Promotes Hepatocellular Carcinoma Cell Growth.","authors":"Jinjing Chen, Carlee A Trindl, Haofeng Ye, Dichun Huang, Aikseng Ooi, Joe G N Garcia, Eli Chapman, Donna D Zhang","doi":"10.1002/mc.23925","DOIUrl":"10.1002/mc.23925","url":null,"abstract":"Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related mortality globally. Current systemic therapies for HCC are limited and often exhibit unsatisfactory efficacy, underscoring the need for novel therapeutic approaches. Nuclear factor erythroid 2-related factor-2 (NRF2), a master transcription factor regulating cellular redox and metabolic homeostasis, is frequently overexpressed in HCC due to mutations in NFE2L2/NRF2 or its negative regulator Kelch-like ECH-associated protein 1 (KEAP1), contributing to tumor progression. In this study, we identify CYP4F11, a member of the Cytochrome P450 family, as a direct target gene of NRF2. CYP4F11, primarily expressed in the liver, is crucial in fatty acid oxidation and eicosanoid metabolism. We demonstrate that CYP4F11 expression is driven by NRF2 and is significantly elevated in HCC patients harboring NFE2L2 gain of function or KEAP1 loss of function mutations. Functionally, CYP4F11 promotes HCC cell growth, and reduced expression of CYP4F11 not only suppresses HCC cell proliferation but also enhances sorafenib-induced HCC cell death. Further, NRF2 inhibition sensitizes HCC to sorafenib through downregulation of CYP4F11. These findings position CYP4F11 as a novel contributor to HCC progression and highlight the potential of targeting the NRF2-CYP4F11 axis for HCC treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1264-1274"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028631","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

Therapeutic Targeting of the Pentose Phosphate Pathway in Colorectal Cancer Using 6-Aminonicotinamide and 5-Fluorouracil. 6-氨基烟碱酰胺和5-氟尿嘧啶治疗结肠直肠癌戊糖磷酸途径的靶向性研究

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-16 DOI: 10.1002/mc.23920

Israa Ahmad Cheikh, Berthe Hayar, Noorhan Ghanem, Lara Al Saleh, Chirine El-Baba, Sadaf Al-Hadeethi, Riyad El-Khoury, Julnar Usta, Nadine Darwiche

{"title":"Therapeutic Targeting of the Pentose Phosphate Pathway in Colorectal Cancer Using 6-Aminonicotinamide and 5-Fluorouracil.","authors":"Israa Ahmad Cheikh, Berthe Hayar, Noorhan Ghanem, Lara Al Saleh, Chirine El-Baba, Sadaf Al-Hadeethi, Riyad El-Khoury, Julnar Usta, Nadine Darwiche","doi":"10.1002/mc.23920","DOIUrl":"10.1002/mc.23920","url":null,"abstract":"Colorectal cancer (CRC) is a significant global health concern with rising incidence and mortality rates. 5-Fluorouracil (5-FU) is the standard chemotherapy for CRC but is often constrained by resistance and toxicity, highlighting the need for more efficient treatments. The pentose phosphate pathway (PPP), a glucose metabolic shunt, is significantly upregulated in CRC to support nucleotide synthesis and redox balance. Therefore, we hypothesized that targeting the PPP decreases CRC cell growth, reduces tumor progression, and improves 5-FU therapy. Consequently, we investigated the anti-tumor activities, cell death mechanism, and mode of action of the PPP inhibitor, 6-aminonicotinamide (6-AN), and 5-FU alone or in combination against CRC. We used human CRC cell lines with different p53 and 5-FU resistance statuses and a CRC xenograft model. Our findings show that 6-AN reduced the viability of human CRC cells independently of their p53 and 5-FU resistance profile, with its effect further enhanced in combination with 5-FU. The 6-AN/5-FU combination treatment synergized by reducing the total dehydrogenase activity of the PPP, inducing oxidative stress, and promoting senescence in CRC cells. Furthermore, 6-AN treatment significantly decreased tumor growth in a CRC xenograft mouse model. However, combining 6-AN with 5-FU did not reduce tumor volume significantly, highlighting the complexities of translating in vitro findings to animal models. These results suggest that interfering with the PPP activity suppresses CRC cell growth and may reduce 5-FU resistance. This study underscores targeting cancer metabolism as a novel therapeutic strategy to minimize drug resistance and to improve CRC therapeutic outcomes.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1222-1235"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991103","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 Value of AURKA and CDK6 Amplification for the Response of Patients With Gastric Cancer to Neoadjuvant Chemotherapy. AURKA和CDK6扩增对胃癌患者新辅助化疗反应的潜在价值

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-13 DOI: 10.1002/mc.23921

Yuen Tan, Yao Xing, Shuai Yuan, Fan Sun, Xiaohui Lin, Simeng Bao, Dongyue Jiang, Jianjun Zhang, Shu-Lan Sun

{"title":"Potential Value of AURKA and CDK6 Amplification for the Response of Patients With Gastric Cancer to Neoadjuvant Chemotherapy.","authors":"Yuen Tan, Yao Xing, Shuai Yuan, Fan Sun, Xiaohui Lin, Simeng Bao, Dongyue Jiang, Jianjun Zhang, Shu-Lan Sun","doi":"10.1002/mc.23921","DOIUrl":"10.1002/mc.23921","url":null,"abstract":"Many patients respond poorly to neoadjuvant chemotherapy (NACT), negatively affecting the surgical success rate. Identifying effective biomarkers and understanding the potential resistance mechanisms are urgently needed. Data of 18 patients with advanced stomach cancer who were treated with NACT categorized according to tumor regression grade into major histological response (MJHR) and nonhistological response (NHR) groups were retrospectively analyzed. Genomic signatures associated with the response to NACT were identified using whole-exome and RNA sequencing. Extraction of molecular signatures revealed increased deficient mismatch repair signature and tumor mutation levels in the NHR group. Compared to the MJHR group, the NHR group was also characterized by a greater number of copy number alterations (p = 0.08), which was further confirmed by RNA sequencing, and upregulation of aurora kinase A (AURKA) (p = 0.05) and cyclin-dependent kinase 6 (CDK6) (p = 0.049). Western blot analysis and immunohistochemical analyses further confirmed high CDK6 (p < 0.01/p < 0.0001) and AURKA (p < 0.01/p < 0.001) expression levels in the NHR group. Finally, palbociclib, an inhibitor of CDK4/6, effectively inhibited the proliferation (p < 0.05) and induced apoptosis of oxaliplatin-resistant gastric cancer cells (p < 0.01) in vitro. These findings support the potential value of AURKA and CDK6 amplification, as well as their effects on the tumor microenvironment, in predicting poor outcomes of NACT in patients with locally advanced gastric cancer. Thus, CDK4/6 inhibitors could be used to treat NACT-resistant patients with gastric cancer.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1195-1208"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029148","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

SDCBP Orchestrated Gastric Cancer Aggression Through Epithelial- Mesenchymal Transition and Macrophages M2 Polarization. SDCBP通过上皮-间质转化和巨噬细胞M2极化介导胃癌侵袭。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-21 DOI: 10.1002/mc.23923

Chan-Yuan Zhao, Feng Liu, Jia-Ming Dong, Cun-Pu Du, Chen-Li Zhang, Chen-Yu Wang, Xiao-Yu Zhang, Quan Zhou, Wei Liu, Ai-Jun Yang, Yong-Ning Zhou, Yun Dang, Li-Na Shang, Min Wang, Min Li

{"title":"SDCBP Orchestrated Gastric Cancer Aggression Through Epithelial- Mesenchymal Transition and Macrophages M2 Polarization.","authors":"Chan-Yuan Zhao, Feng Liu, Jia-Ming Dong, Cun-Pu Du, Chen-Li Zhang, Chen-Yu Wang, Xiao-Yu Zhang, Quan Zhou, Wei Liu, Ai-Jun Yang, Yong-Ning Zhou, Yun Dang, Li-Na Shang, Min Wang, Min Li","doi":"10.1002/mc.23923","DOIUrl":"10.1002/mc.23923","url":null,"abstract":"Gastric cancer remains a significant global health burden with limited treatment options and high mortality. Syndecan-binding protein (SDCBP), a scaffolding protein involved in tumor differentiation, has attracted attention as a potential therapeutic target in cancers. However, its precise role in gastric cancer progression is not fully understood. In this study, through bioinformatics analysis and gastric cancer samples detection, we discovered that SDCBP was highly expressed in gastric cancer tissues, which was correlated with clinicopathological features such as tumor invasion depth and distant metastasis, and exhibited heterogeneity across histological or molecular subtypes. Elevated SDCBP expression promoted the proliferation, invasion and migration of gastric cancer cells, and modulated epithelial-mesenchymal transition (EMT) via the ERK signaling pathway. Xenograft experiments in mice confirmed that inhibiting SDCBP or ERK signaling could delay cancer progression. We also found that gastric cancer cells with SDCBP knockdown were able to inhibit the M2 polarization of cocultured macrophages, reduce chemotaxis and enhance phagocytosis of macrophages. Therefore, SDCBP plays a crucial role in driving gastric cancer progression. Targeting SDCBP in gastric cancer can partially reverse the malignant phenotype, and SDCBP is expected to be a promising therapeutic target for gastric cancer.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1247-1263"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034020","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

Diagnostic Utility of microRNA146a and microRNA19a in Gallbladder Cancer: A Pilot Study. 胆囊癌中 microRNA146a 和 microRNA19a 的诊断效用：一项试点研究

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-06 DOI: 10.1002/mc.23916

Rahul Saxena, Sarath Krishnan Mp, Amit Gupta, Sweety Gupta, Anissa A Mirza, Nitin Chaudhary, Bela Goyal

{"title":"Diagnostic Utility of microRNA146a and microRNA19a in Gallbladder Cancer: A Pilot Study.","authors":"Rahul Saxena, Sarath Krishnan Mp, Amit Gupta, Sweety Gupta, Anissa A Mirza, Nitin Chaudhary, Bela Goyal","doi":"10.1002/mc.23916","DOIUrl":"10.1002/mc.23916","url":null,"abstract":"Gallbladder cancer (GBC) is a rare but aggressive malignancy, often diagnosed at advanced stages due to its asymptomatic progression and lack of reliable biomarkers. Chronic inflammation plays a crucial role in its pathogenesis, with inflammatory pathways contributing to tumor development. This study evaluates the diagnostic potential of microRNA19a and microRNA146a, key regulators of inflammatory and oncogenic pathways, in distinguishing GBC from cholelithiasis and healthy controls. An observational analytical study was conducted on 60 participants, divided into three groups: GBC (n = 20), cholelithiasis (n = 20), and non-dysplastic/healthy controls (n = 20). microRNA expression levels in tissue and plasma samples were quantified using RT-PCR and qPCR, with ΔCq values normalized to U6 RNA. Receiver Operating Characteristic (ROC) analysis assessed diagnostic performance, and correlations between tissue and plasma expression levels were examined. Most GBC cases (65%) were diagnosed at Stage IV, with 75% showing liver infiltration. microRNA19a and microRNA146a expression levels were significantly elevated in GBC tissues compared to the other groups (p < 0.0001). Plasma microRNA146a demonstrated high diagnostic accuracy, with an AUC of 0.953, sensitivity of 80%, and specificity of 95%, outperforming microRNA19a (AUC 0.388, sensitivity 20%, specificity 95%). Strong positive correlations between tissue and plasma expression were observed for microRNA146a (r = 0.693, p = 0.0007) and microRNA19a (r = 0.564, p = 0.010), supporting their potential as circulating biomarkers. microRNA146a exhibits good diagnostic utility in differentiating GBC, particularly in advanced disease stages, while microRNA19a reflects inflammation-driven carcinogenesis. Plasma-based microRNA detection offers a promising noninvasive diagnostic approach for early and accurate GBC detection. Further large-scale studies are warranted to validate these biomarkers and explore their therapeutic implications.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1160-1167"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795705","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

Adipose Secreted Slit2-C Suppresses Breast Cancer Invasion Through cAMP/PKA Transition. 脂肪分泌的Slit2-C通过cAMP/PKA转换抑制乳腺癌侵袭。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-01 DOI: 10.1002/mc.23915

Haolin Hu, Kexuan Li, Lifei Han, Yangyang Gu, Zhenling Ji

{"title":"Adipose Secreted Slit2-C Suppresses Breast Cancer Invasion Through cAMP/PKA Transition.","authors":"Haolin Hu, Kexuan Li, Lifei Han, Yangyang Gu, Zhenling Ji","doi":"10.1002/mc.23915","DOIUrl":"10.1002/mc.23915","url":null,"abstract":"Adipose tissue activation plays a positive role in breast cancer outcomes, consistent with the improved outcomes observed through exercise and weight loss mediated by brown and beige fat. However, the underlying mechanism of this process remains unclear. C-terminal fragment of Slit2 (Slit2-C), endogenously produced by brown or beige adipose cells could increase the thermogenic process of adipose cells in autocrine and paracrine manners. Here, we show that Slit2-C dominantly reduces breast cancer cell invasion through cAMP/PKA mediated inhibition of epithelial-mesenchymal transition. In the process, Slit2-C plays a vital role as a positive regulator of cAMP/PKA signaling in breast cancer. As a result, the overexpression of Slit2-C leads to a reduction in cancer cell invasion and an increase in both the epithelial phenotype and thermogenesis. Besides, inhibiting PKA phosphorylation with H89 reversed the reduced invasion process seen in human breast cancer cells overexpressing Slit2-C, which suggests that the effect of Slit2-C on reducing invasion is mediated through the activation of PKA signaling. Taken together, our study suggests that the modulation of the Slit2-C/cAMP/PKA axis might be a potential targeting therapeutic intervention in aggressive breast cancers.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1149-1159"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764490","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