Carcinogenesis最新文献_第10页

Correction to: (-)-Epigallocatechin-3-gallate and DZNep reduce polycomb protein level via a proteasome-dependent mechanism in skin cancer cells. 更正：(-)-表没食子儿茶素-3-棓酸盐和 DZNep 通过蛋白酶体依赖机制降低皮肤癌细胞中多聚体蛋白的水平。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-05-19 DOI: 10.1093/carcin/bgad045

引用次数: 0

E3 ubiquitin ligase RNF148 functions as an oncogene in colorectal cancer by ubiquitination-mediated degradation of CHAC2. E3泛素连接酶RNF148通过泛素化介导的CHAC2降解在结直肠癌中发挥癌基因的功能。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgae002

Shuiping Liu, Lvjia Zhuo, Lu Chen, Ying He, Xudong Chen, Hao Zhang, Yuan Zhou, Ziheng Ni, Shujuan Zhao, Xiaotong Hu

{"title":"E3 ubiquitin ligase RNF148 functions as an oncogene in colorectal cancer by ubiquitination-mediated degradation of CHAC2.","authors":"Shuiping Liu, Lvjia Zhuo, Lu Chen, Ying He, Xudong Chen, Hao Zhang, Yuan Zhou, Ziheng Ni, Shujuan Zhao, Xiaotong Hu","doi":"10.1093/carcin/bgae002","DOIUrl":"10.1093/carcin/bgae002","url":null,"abstract":"We previously reported that RNF148 was involved in the ubiquitination-mediated degradation of CHAC2. However, its molecular mechanism was not determined. In this study, we investigated the role and mechanism of RNF148 in the progression of colorectal cancer (CRC), especially in the process of ubiquitination-mediated degradation of CHAC2. Our results revealed that RNF148 was upregulated in most CRC tissues, and its expression significantly correlated with the 3-year overall survival rate and most clinicopathological parameters of CRC patients. Furthermore, RNF148 served as an independent prognostic biomarker of CRC and promoted CRC cell proliferation and migration while inhibiting cell apoptosis and sensitivity to 5-FU. Mechanistically, RNF148 used its protease-associated domain to bind to the CHAC domain of CHAC2 and target it for degradation. In addition, we identified two phosphorylation and three ubiquitination residues of CHAC2 and identified Y118 and K102 as the critical phosphorylation and ubiquitination residues, respectively. We also identified CHAC2's and RNF148's interacting proteins and discovered their potential interaction network. In conclusion, our current study unveiled the role of RNF148 in CRC and the mechanism of RNF148 in the ubiquitination-mediated degradation of CHAC2, which shed light on providing potential prognostic biomarkers and molecular targets for CRC patients.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"247-261"},"PeriodicalIF":4.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402014","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}

引用次数: 0

MAGP1 maintains tumorigenicity and angiogenesis of laryngeal cancer by activating Wnt/β-catenin/MMP7 pathway. MAGP1 通过激活 Wnt/β-catenin/MMP7 通路维持喉癌的致瘤性和血管生成。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgad003

Fei Lv, Xiaoqi Li, Ying Wang, Liying Hao

引用次数: 0

ITGA2 as a prognostic factor of glioma promotes GSCs invasion and EMT by activating STAT3 phosphorylation. ITGA2 是胶质瘤的一个预后因子，它通过激活 STAT3 磷酸化促进 GSCs 的侵袭和 EMT。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgad096

Jin Zhang, Ruinan Li, Haibin Zhang, Shanshan Wang, Yuanli Zhao

{"title":"ITGA2 as a prognostic factor of glioma promotes GSCs invasion and EMT by activating STAT3 phosphorylation.","authors":"Jin Zhang, Ruinan Li, Haibin Zhang, Shanshan Wang, Yuanli Zhao","doi":"10.1093/carcin/bgad096","DOIUrl":"10.1093/carcin/bgad096","url":null,"abstract":"Glioma is the most common malignant brain tumor in adults with a high mortality and recurrence rate. Integrin alpha 2 (ITGA2) is involved in cell adhesion, stem cell regulation, angiogenesis and immune cell function. The role of ITGA2 in glioma malignant invasion remains unknown. The function and clinical relevance of ITGA2 were analysed by bioinformatics databases. The expression of ITGA2 in parent cells and GSCs was detected by flow cytometry and immunofluorescence double staining. The role of ITGA2 on the malignant phenotype of GSCs and epithelial-mesenchymal transition (EMT) was identified by stem cell function assays and Western blot. The effect of ITGA2 on glioma progression in vivo was determined by the intracranial orthotopic xenograft model. Immunohistochemistry, Spearman correlation and Kaplan-Meier were used to analyse the relationship of ITGA2 with clinical features and glioma prognosis. Biological analysis showed that ITGA2 might be related to cell invasion and migration. ITGA2, enriched in GSCs and co-expressed with SOX2, promoted the invasion and migration of GSCs by activating STAT3 phosphorylation and enhancing EMT. ITGA2 knockout suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice. In addition, the expression level of ITGA2 was significantly correlated to the grade of malignancy, N-cadherin and Ki67. High expression of ITGA2 indicated a worse prognosis of glioma patients. As a biomarker for the prediction of prognosis, ITGA2 promotes the malignant invasion of GSCs by activating STAT3 phosphorylation and enhancing EMT, leading to tumor recurrence and poor prognosis.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"235-246"},"PeriodicalIF":4.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032183","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}

引用次数: 0

Functional genetic variants of the disulfidptosis-related INF2 gene predict survival of hepatitis B virus-related hepatocellular carcinoma. 二硫化相关 INF2 基因的功能性遗传变异可预测乙型肝炎病毒相关肝细胞癌的存活率。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgae003

Junjie Wei, Qiuping Wen, Shicheng Zhan, Ji Cao, Yanji Jiang, Jiawei Lian, Yuejiao Mai, Moqin Qiu, Yingchun Liu, Peiqin Chen, Qiuling Lin, Xiaoxia Wei, Yuying Wei, Qiongguang Huang, Ruoxin Zhang, Songqing He, Guandou Yuan, Qingyi Wei, Zihan Zhou, Hongping Yu

{"title":"Functional genetic variants of the disulfidptosis-related INF2 gene predict survival of hepatitis B virus-related hepatocellular carcinoma.","authors":"Junjie Wei, Qiuping Wen, Shicheng Zhan, Ji Cao, Yanji Jiang, Jiawei Lian, Yuejiao Mai, Moqin Qiu, Yingchun Liu, Peiqin Chen, Qiuling Lin, Xiaoxia Wei, Yuying Wei, Qiongguang Huang, Ruoxin Zhang, Songqing He, Guandou Yuan, Qingyi Wei, Zihan Zhou, Hongping Yu","doi":"10.1093/carcin/bgae003","DOIUrl":"10.1093/carcin/bgae003","url":null,"abstract":"Disulfidptosis is a novel form of programmed cell death involved in migration and invasion of cancer cells, but few studies investigated the roles of genetic variants in disulfidptosis-related genes in survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We used Cox proportional hazards regression analyses, Kaplan-Meier curves and receiver operating characteristic curves to assess effects of genetic variants in 14 disulfidptosis-related genes on overall survival of 866 HBV-HCC patients. The Bayesian false discovery probability was used for multiple testing corrections. We also investigated biological mechanisms of the significant variants through expression quantitative trait loci analyses using the data from publicly available databases, luciferase reporter assays and differential expression analyses. As a result, we identified two independently functional single nucleotide polymorphisms (SNPs) (INF2 rs4072285 G > A and INF2 rs4444271 A > T) that predicted overall survival of HBV-HCC patients, with adjusted hazard ratios of 1.60 (95% CI = 1.22-2.11, P = 0.001) and 1.50 (95% CI = 1.80-1.90, P < 0.001), respectively, after multiple testing correction. Luciferase reporter assays indicated that both INF2 rs4072285 A and INF2 rs4444271 T alleles increased INF2 mRNA expression levels (P < 0.001) that were also higher in HCC tumor tissues than in adjacent normal tissues (P < 0.001); such elevated INF2 expression levels were associated with a poorer survival of HBV-HCC patients (P < 0.001) in the TCGA database. In summary, this study supported that INF2 rs4072285 and INF2 rs4444271 may be novel biomarkers for survival of HBV-HCC patients.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"199-209"},"PeriodicalIF":4.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545760","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}

引用次数: 0

Sitravatinib combined with PD-1 blockade enhances cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma. 西拉瓦替尼联合阻断PD1可增强食管癌中M2 - M1肿瘤巨噬细胞的细胞毒性t细胞浸润。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgad087

Ryan Sweeney, Ashten N Omstead, John T Fitzpatrick, Ping Zheng, Anastasia Gorbunova, Erin E Grayhack, Arul Goel, Alisha F Khan, Juliann E Kosovec, Patrick L Wagner, Blair A Jobe, Ronan J Kelly, Ali H Zaidi

{"title":"Sitravatinib combined with PD-1 blockade enhances cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma.","authors":"Ryan Sweeney, Ashten N Omstead, John T Fitzpatrick, Ping Zheng, Anastasia Gorbunova, Erin E Grayhack, Arul Goel, Alisha F Khan, Juliann E Kosovec, Patrick L Wagner, Blair A Jobe, Ronan J Kelly, Ali H Zaidi","doi":"10.1093/carcin/bgad087","DOIUrl":"10.1093/carcin/bgad087","url":null,"abstract":"Esophageal adenocarcinoma (EAC) is a leading cause of cancer-related mortality. Sitravatinib is a novel multi-gene tyrosine kinase inhibitor (TKI) that targets tumor-associated macrophage (TAM) receptors, VEGF, PDGF and c-Kit. Currently, sitravatinib is actively being studied in clinical trials across solid tumors and other TKIs have shown efficacy in combination with immune checkpoint inhibitors (ICI) in cancer models. In this study, we investigated the anti-tumor activity of sitravatinib alone and in combination with PD-1 blockade in an EAC rat model. Treatment response was evaluated by mortality, pre- and post-treatment MRI, gene expression, immunofluorescence and immunohistochemistry. Our results demonstrated adequate safety and significant tumor shrinkage in animals treated with sitravatinib, and more profoundly, sitravatinib and PD-1 inhibitor, AUNP-12 (P < 0.01). Suppression of TAM receptors resulted in increased gene expression of pro-inflammatory cytokines and decreased expression of anti-inflammatory cytokines, enhanced infiltration of CD8+ T cells, and M2 to M1 macrophage phenotype repolarization in the tumor microenvironment of treated animals (P < 0.01). Moreover, endpoint immunohistochemistry staining corroborated the anti-tumor activity by downregulation of Ki67 and upregulation of Caspase-3 in the treated animals. Additionally, pretreatment gene expression of TAM receptors and PD-L1 were significantly higher in major responders compared with the non-responders, in animals that received sitravatinib and AUNP-12 (P < 0.02), confirming that TAM suppression enhances the efficacy of PD-1 blockade. In conclusion, this study proposes a promising immunomodulatory strategy using a multi-gene TKI to overcome developed resistance to an ICI in EAC, establishing rationale for future clinical development.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"210-219"},"PeriodicalIF":4.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457987","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}

引用次数: 0

Actinomycin D synergizes with Doxorubicin in triple-negative breast cancer by inducing P53-dependent cell apoptosis. 放线菌素D与阿霉素协同作用诱导p53依赖性细胞凋亡治疗三阴性乳腺癌

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgad086

Hong Yang, Sha Li, Wan Li, Yihui Yang, Yizhi Zhang, Sen Zhang, Yue Hao, Wanxin Cao, Fang Xu, Hongquan Wang, Guanhua Du, Jinhua Wang

{"title":"Actinomycin D synergizes with Doxorubicin in triple-negative breast cancer by inducing P53-dependent cell apoptosis.","authors":"Hong Yang, Sha Li, Wan Li, Yihui Yang, Yizhi Zhang, Sen Zhang, Yue Hao, Wanxin Cao, Fang Xu, Hongquan Wang, Guanhua Du, Jinhua Wang","doi":"10.1093/carcin/bgad086","DOIUrl":"10.1093/carcin/bgad086","url":null,"abstract":"Objectives: There are three major subtypes of breast cancer, ER+, HER2+ and triple-negative breast cancer (TNBC), namely ER-, PR-, HER2-. TNBC is the most aggressive breast cancer with poor prognosis and no target drug up to now. Actinomycin D (ActD) is a bioactive metabolite of marine bacteria that has been reported to have antitumor activity. The aim of study is to investigate whether ActD has a synergetic effect on TNBC with Doxorubicin (Dox), the major chemotherapeutic drug for TNBC, and explore the underlying mechanism.Methods: TNBC cell lines HCC1937, MDA-MB-436 and nude mice were used in the study. Drug synergy determination, LDH assay, MMP assay, Hoechst 33342 staining, Flow cytometry, Flexible docking and CESTA assay were carried out. The expression of proteins associated with apoptosis was checked by Western blot and siRNA experiments were performed to investigate the role of P53 and PUMA induced by drugs.Results: There was much higher apoptosis rate of cells in the ActD + Dox group than that in ActD group or Dox group. Expression of MDM2 and BCL-2 was reduced while expression of P53, PUMA and BAX were increased in the groups treated with ActD + Dox or Dox compared to the control group. Furthermore, P53 siRNA or PUMA siRNA tremendously abrogated the cell apoptosis in the groups treated by ActD, Dox and ActD + Dox. Flexible docking and CESTA showed that ActD can bind MDM2.Conclusions: ActD had a synergetic effect on TNBC with Dox via P53-dependent apoptosis and it may be a new choice for treatment of TNBC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"262-273"},"PeriodicalIF":4.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298480","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}

引用次数: 0

Surgical stress induced tumor immune suppressive environment. 手术应激诱导的肿瘤免疫抑制环境。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgae012

Fan Yang, Qing Hua, Xiaoyan Zhu, Pingbo Xu

引用次数: 0

Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis. 剪接因子ESRP1衍生circ_0068162通过miR-186/JAG轴促进口腔鳞状细胞癌的进展。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-03-11 DOI: 10.1093/carcin/bgad082

Shuai Chen, Yingrui Zong, Zhenzhen Hou, Zhifen Deng, Zongping Xia

{"title":"Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis.","authors":"Shuai Chen, Yingrui Zong, Zhenzhen Hou, Zhifen Deng, Zongping Xia","doi":"10.1093/carcin/bgad082","DOIUrl":"10.1093/carcin/bgad082","url":null,"abstract":"Objectives: Oral squamous cell carcinoma (OSCC) is a common malignancy in the oral and maxillofacial regions with an increasing incidence rate. Circular RNA (circRNA) is a recently discovered long-chain non-coding RNA family member. The objective of this study was to analyze the role of circ_0068162 in OSCC development.Methods: We downloaded sample data GSE145608 from the Gene Expression Omnibus database. Online databases Starbase, TargetScan and miRDB were used to predict the target microRNAs (miRNAs) and genes. Cell viability and proliferation were assessed using the CCK-8 and EdU assays, respectively. Cell migration and invasion abilities were detected using transwell assay. The double luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the interaction relationship between the identified target molecules. RNase R and actinomycin D treatment were performed to analyze the stability of circ_0068162.Results: We found that circ_0068162 was overexpressed in the cytoplasm of OSCC cells and clinical OSCC tissues. Knockdown of circ_0068162 inhibited the growth, migration and invasion of OSCC cells. We also identified miR-186 as the target miRNA of circ_0068162, and JAG1 and JAG2 as the target genes of miR-186. The miR-186 inhibitor rescued the effects of sh-circ_0068162 and JAG1/JAG2 overexpression rescued the effects of miR-186 mimic in OSCC cells. Furthermore, ESRP1 promoted the biosynthesis of circ_0068162.Conclusions: The circ_0068162/miR-186/JAGs/ESRP1 feedback loop is closely related to OSCC development.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"107-118"},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590305","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}

引用次数: 0

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-03-11 DOI: 10.1093/carcin/bgad094

Yutaro Hori, Tomoaki Yoh, Hiroto Nishino, Keisuke Okura, Makoto Kurimoto, Yuichi Takamatsu, Motohiko Satoh, Takahiro Nishio, Yukinori Koyama, Takamichi Ishii, Keiko Iwaisako, Satoru Seo, Etsuro Hatano

{"title":"Ferroptosis-related gene glutathione peroxidase 4 promotes reprogramming of glucose metabolism via Akt-mTOR axis in intrahepatic cholangiocarcinoma.","authors":"Yutaro Hori, Tomoaki Yoh, Hiroto Nishino, Keisuke Okura, Makoto Kurimoto, Yuichi Takamatsu, Motohiko Satoh, Takahiro Nishio, Yukinori Koyama, Takamichi Ishii, Keiko Iwaisako, Satoru Seo, Etsuro Hatano","doi":"10.1093/carcin/bgad094","DOIUrl":"10.1093/carcin/bgad094","url":null,"abstract":"The role of the ferroptosis-related gene glutathione peroxidase 4 (GPX4) in oncology has been extensively investigated. However, the clinical implications of GPX4 in patients with intrahepatic cholangiocarcinoma (ICC) remain unknown. This study aimed to evaluate the prognostic impact of GPX4 and its underlying molecular mechanisms in patients with ICC. Fifty-seven patients who underwent surgical resection for ICC between 2010 and 2017 were retrospectively analyzed. Based on the immunohistochemistry, patients were divided into GPX4 high (n = 15) and low (n = 42) groups, and clinical outcomes were assessed. Furthermore, the roles of GPX4 in cell proliferation, migration and gene expression were analyzed in ICC cell lines in vitro and in vivo. The results from clinical study showed that GPX4 high group showed significant associations with high SUVmax on 18F-fluorodeoxyglucose-positron emission tomography (≥8.0, P = 0.017), multiple tumors (P = 0.004), and showed glucose transporter 1 (GLUT1) high expression with a trend toward significance (P = 0.053). Overall and recurrence-free survival in the GPX4 high expression group were significantly worse than those in the GPX4 low expression group (P = 0.038 and P < 0.001, respectively). In the experimental study, inhibition of GPX4 attenuated cell proliferation and migration in ICC cell lines. Inhibition of GPX4 also decreased the expression of glucose metabolism-related genes, such as GLUT1 or HIF1α. Mechanistically, these molecular changes are regulated in Akt-mechanistic targets of rapamycin axis. In conclusion, this study suggested the pivotal value of GPX4 serving as a prognostic marker for patients with ICC. Furthermore, GPX4 can mediate glucose metabolism of ICC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"119-130"},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828319","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}

引用次数: 0