Molecular Carcinogenesis最新文献_第5页

RETRACTION: SENP2 Suppresses Epithelial-Mesenchymal Transition of Bladder Cancer Cells Through deSUMOylation of TGF-βRI. 撤回：SENP2通过TGF-βRI的去氧修饰抑制膀胱癌细胞上皮-间质转化。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-25 DOI: 10.1002/mc.70038

{"title":"RETRACTION: SENP2 Suppresses Epithelial-Mesenchymal Transition of Bladder Cancer Cells Through deSUMOylation of TGF-βRI.","authors":"","doi":"10.1002/mc.70038","DOIUrl":"https://doi.org/10.1002/mc.70038","url":null,"abstract":"Retraction: M. Tan, D. Zhang, E. Zhang, D. Xu, Z. Liu, J. Qiu, Y. Fan, and B. Shen, \"SENP2 Suppresses Epithelial-Mesenchymal Transition of Bladder Cancer Cells Through deSUMOylation of TGF-βRI,\" Molecular Carcinogenesis 56, no. 10 (2017): 2332-2341. https://doi.org/10.1002/mc.22687. The above article, published online on 02 June 2017, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by Wiley Periodicals LLC. A third party reported to the journal that image elements in Figure 2E of this article had been duplicated and manipulated from a previously published article by a different group of authors and reporting different experimental conditions (Mani et al. 2007 [https://doi.org/10.1073/pnas.0703900104]). Further investigation by the publisher confirmed this duplication and also detected additional duplications between the T24-Vector panel of Figure 5A and the first panel of Figure 5B, as well as duplication and rotation of image elements in the T24-SENP2 panel of Figure 5A and the third panel of Figure 5B. The authors responded to an inquiry by the publisher and stated that there were no issues of duplication between different articles and that the duplications in Figure 5 may have been caused by errors during image preparation. However, the authors were unable to provide original, unmodified data or images for the experiments reported. The retraction has been agreed to because of the duplication of images from another article, as well as duplication and rotation of images and image elements within the same article, which fundamentally compromises the reported conclusions. The authors have stated their consent to the retraction. The authors disagree with the retraction as they have stated they do not agree that image elements were duplicated in Figure 2E.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962190","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

Folic Acid Protects Against Radiation-Induced Lung Injury by Suppressing Senescence of Lung Epithelial Cells. 叶酸通过抑制肺上皮细胞衰老来预防辐射引起的肺损伤。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-25 DOI: 10.1002/mc.70027

Li Zhong, Xin Guo, Yuxin Yang, Dan Jian, Yang Peng, Xianfeng Lu

{"title":"Folic Acid Protects Against Radiation-Induced Lung Injury by Suppressing Senescence of Lung Epithelial Cells.","authors":"Li Zhong, Xin Guo, Yuxin Yang, Dan Jian, Yang Peng, Xianfeng Lu","doi":"10.1002/mc.70027","DOIUrl":"https://doi.org/10.1002/mc.70027","url":null,"abstract":"Radiation-induced lung injury (RILI) is a prevalent complication of thoracic tumor radiotherapy, severely compromising treatment efficacy and the patients' quality of life, yet effective prevention or treatment strategies remain elusive. Folic acid (FA), a water-soluble vitamin, plays critical roles in DNA synthesis/repair, cell cycle regulation, epigenetic regulation via methylation, oxidative stress response, and embryonic development. However, its radioprotective role has not been systematically elucidated. This study aimed to investigate its effects and molecular mechanisms during RILI. The RILI murine model showed that folic acid supplementation significantly alleviated radiation-induced lung tissue damage, body weight loss, and inflammatory cell infiltration. Meanwhile, folic acid mitigated radiation-induced DNA damage and cellular senescence in lung tissues and lung epithelial cell lines. RNA sequencing identified a 29-gene SASP signature (including CCL5, CXCL2, CXCL10), which was significantly suppressed by folic acid in irradiated lungs. Moreover, folic acid inhibited SASP production by suppressing the phosphorylation of P38 MAPK/NF-κB signaling pathway. By integrating in vivo and in vitro models, we revealed that folic acid exerts its radioprotective effects by reducing cellular senescence and the production of SASP. Taken together, these findings indicated that folic acid is potentially a novel therapeutic strategy for RILI.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962132","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-150-5p Regulates Merkel Cell Carcinoma Progression by Targeting FTO That Stabilizes CTNNB1 via m⁶A Modification. miR-150-5p通过m6A修饰稳定CTNNB1的FTO调控默克尔细胞癌进展。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-22 DOI: 10.1002/mc.70036

Bin Zheng, Min Li, Zixuan Gao, Yajie Yang, Kaikai Guo, Huijie Gao, Yungang Zhao, Weng-Onn Lui, Hong Xie

{"title":"miR-150-5p Regulates Merkel Cell Carcinoma Progression by Targeting FTO That Stabilizes CTNNB1 via m6A Modification.","authors":"Bin Zheng, Min Li, Zixuan Gao, Yajie Yang, Kaikai Guo, Huijie Gao, Yungang Zhao, Weng-Onn Lui, Hong Xie","doi":"10.1002/mc.70036","DOIUrl":"https://doi.org/10.1002/mc.70036","url":null,"abstract":"MicroRNAs (miRNAs) are small regulatory molecules playing important roles in different physiological and pathological processes, but only several miRNAs were functionally characterized in Merkel cell carcinoma (MCC). We previously identified miR-150-5p as one of the differentially expressed miRNAs between MCC metastases and primary tumors. In the present study, we further investigated the functional role of miR-150-5p in MCC progression. Our results revealed that miR-150-5p suppresses the migratory and invasive properties of MCC cells. We identified RNA N6-methyladenosine (m6A) demethylase FTO as a direct target of miR-150-5p. Functionally, we showed that FTO enhances proliferative, migratory and invasive properties of MCC cells, and rescued the antitumor effects induced by miR-150-5p. Mechanistically, we demonstrated that FTO stabilizes CTNNB1 transcripts via its m6A demethylation activity. Silencing the m6A reader YTHDF2 increased, while its overexpression decreased CTNNB1 mRNA and protein levels. Furthermore, the RNA immunoprecipitation assays demonstrated the interaction between CTNNB1 mRNA and YTHDF2. Together, these results suggest that FTO stabilizes CTNNB1 in an m6A-dependent manner. In conclusion, our findings uncover the role of miR-150-5p and its target FTO in MCC progression, suggesting the potential of targeting FTO signaling for MCC therapy.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962159","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

GDF15-Mediated Regulation of Ferroptosis: Unraveling the p62/Keap1/Nrf2 Pathway in Gastric Cancer Development. gdf15介导的铁下垂调控：揭示p62/Keap1/Nrf2通路在胃癌发展中的作用。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-21 DOI: 10.1002/mc.70037

Lixia Yang, Hong Li, Yun Yang, Liping Dong, Yanqiong Li, Youhua Lv

{"title":"GDF15-Mediated Regulation of Ferroptosis: Unraveling the p62/Keap1/Nrf2 Pathway in Gastric Cancer Development.","authors":"Lixia Yang, Hong Li, Yun Yang, Liping Dong, Yanqiong Li, Youhua Lv","doi":"10.1002/mc.70037","DOIUrl":"https://doi.org/10.1002/mc.70037","url":null,"abstract":"Gastric cancer (GC) is a highly prevalent and lethal malignancy. This study aims to investigate the role of Growth Differentiation Factor 15 (GDF15) in regulating ferroptosis through the p62/Keap1/Nrf2 pathway and to elucidate its impact on GC progression. GDF15 levels were assessed via Western blot (WB) analysis in both human gastric mucosal cells and GC cell lines. Cellular viability and growth were evaluated using CCK-8 assays and colony formation experiments. Cell migration and invasion capabilities were assessed using wound healing and Transwell assays. Levels of ROS, MDA, GSH, GPX4, and Fe²⁺ in cells were measured using assay kits. JC-1 method was utilized for evaluating mitochondrial membrane potential. Tumor weight changes were recorded in BALB/c nude mouse models. GDF15 was highly expressed in GC cells, and sh-GDF15 inhibited the growth and metastasis of GC cells, increased the expression of ROS and MDA in cells, promoted cell ferroptosis, and inhibited the p62/Keap1/Nrf2 pathway in cells (p < 0.05). Compared to the sh-GDF15 group, treatment with the Nrf2 activator, NK-252 reduced ROS and MDA levels, suppressed ferroptosis, and enhanced the activation of the p62/Keap1/Nrf2 signaling pathway in GC cells. In GC tissues, the sh-GDF15 group showed reduced tumor volume and weight, elevated Keap1, ROS, and MDA expression, decreased p62 and Nrf2 levels, and increased ferroptosis, which were reversed by the addition of NK-252 (p < 0.05). Conclusively, silencing GDF15 inhibits the p62/Keap1/Nrf2 pathway, promoting ferroptosis and suppressing GC progression.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962161","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

Independent Clonal Origin in Early-Stage Bilateral Papillary Thyroid Cancer: Evidence From Nuclear and Mitochondrial Genome Analysis. 早期双侧乳头状甲状腺癌的独立克隆起源：来自核和线粒体基因组分析的证据。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-19 DOI: 10.1002/mc.70031

Xingyun Su, Jimeng Yuan, Xianmeng Chen, Shitu Chen, Xumeng Wang, Jie Zhou, Lisong Teng, Feng Zhang, Weibin Wang

{"title":"Independent Clonal Origin in Early-Stage Bilateral Papillary Thyroid Cancer: Evidence From Nuclear and Mitochondrial Genome Analysis.","authors":"Xingyun Su, Jimeng Yuan, Xianmeng Chen, Shitu Chen, Xumeng Wang, Jie Zhou, Lisong Teng, Feng Zhang, Weibin Wang","doi":"10.1002/mc.70031","DOIUrl":"10.1002/mc.70031","url":null,"abstract":"Papillary thyroid cancer (PTC) often presents as anatomically distinct foci in bilateral lobes. However, it remains controversial whether these foci arise independently from distinct malignant progenitor cells or result from the dissemination of the primary lesion. Fifteen pairs of bilateral PTC at Stage I were enrolled, and sequencing was performed using a 437-cancer-gene panel (Geneseeq). The entire mitochondrial DNA (mtDNA) was also sequenced and analyzed. The genetic alterations and molecular profiles were comprehensively analyzed and compared between the paired bilateral tumors. Fourty-eight mutations were detected in the nuclear genome, all of which were somatic and heteroplasmic. Among these, BRAFV600E mutation was predominant (25/30, 83.3%). In mtDNA, three mutations (10963A-C, 13193T-C, 13341 C-G) were identified as novel, seven heteroplasmic mutations were detected including six somatic mutations. Discordant genetic alterations were observed between the paired tumors in 86.7% (13/15) of bilateral PTC cases. Our results reveal that the majority of early-stage bilateral PTCs develop from independent malignant clones harboring different genetic backgrounds, which provides insights into the pathogenesis of bilateral PTCs and supports individualized clinical decision-making.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883239","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

Noncanonical Pathways of Proteasome Inhibition in HPV-Negative Head & Neck Cancer. hpv阴性头颈癌中蛋白酶体抑制的非典型途径。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-19 DOI: 10.1002/mc.70029

Hye-Yeon Lee, Ji-Yeong Kim, Zhiyong Wang, Panomwat Amornphimoltham, J Silvio Gutkind, Woo-Jin Jeong

{"title":"Noncanonical Pathways of Proteasome Inhibition in HPV-Negative Head & Neck Cancer.","authors":"Hye-Yeon Lee, Ji-Yeong Kim, Zhiyong Wang, Panomwat Amornphimoltham, J Silvio Gutkind, Woo-Jin Jeong","doi":"10.1002/mc.70029","DOIUrl":"10.1002/mc.70029","url":null,"abstract":"Carfilzomib, a second-generation proteasome inhibitor approved for the treatment of multiple myeloma, is a highly potent and selective inhibitor of the CT-L activity of the i20S proteasome. Several studies have shown that carfilzomib (CFZ) can bypass resistance to bortezomib; however, its impact on squamous cell carcinoma of the head and neck is not well understood. This study aimed to evaluate the anticancer potential of CFZ in head and neck cancer cells (HNSCC) by examining its effects on proliferation, apoptosis, and the underlying mechanisms in both HPV-positive and HPV-negative HNSCC. In Vitro validation of CFZ showed an IC50 that was more than fourfold lower in HPV-negative CAL-27 than other HNSCC cell lines. In addition, CFZ inhibited p-Akt and p-S6 and activated p21, which increased growth inhibition and apoptosis in CAL-27 cells. In mice bearing xenografted HPV-negative CAL-27 cells, we confirmed that CFZ reduced tumor growth. Collectively, the cytotoxic effects induced by CFZ involve cell growth inhibition and apoptosis via the PI3K/AKT/mTOR and p21 signaling pathways. This suggests that CFZ is a novel therapeutic agent that can overcome the existing cisplatin resistance used in the treatment of HPV-negative HNSCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883240","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 Posttranslational Modifications in the Tumor Stromal Microenvironment for Antitumor Therapy. 靶向肿瘤间质微环境翻译后修饰的抗肿瘤治疗。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-19 DOI: 10.1002/mc.70030

Huiguo Qing, Xiangyan Jiang, Yong Ma, Zongrui Xing, Yuxia Wu, Keshen Wang, Hongtai Cao, Zuoyi Jiao, Zeyuan Yu

引用次数: 0

TRAF6 Exerts Tumor-Promoting Effects via Genetic and Autophagic Modulation in Gastric Cancer. TRAF6通过基因和自噬调节在胃癌中发挥促瘤作用。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-19 DOI: 10.1002/mc.70032

Yifan Zou, Zhenguang Mao, Jianghao Xu, Weizhi Wang, Zhihao Wang, Jianghong Dai, Rui Zheng, Mulong Du, Zhengdong Zhang

{"title":"TRAF6 Exerts Tumor-Promoting Effects via Genetic and Autophagic Modulation in Gastric Cancer.","authors":"Yifan Zou, Zhenguang Mao, Jianghao Xu, Weizhi Wang, Zhihao Wang, Jianghong Dai, Rui Zheng, Mulong Du, Zhengdong Zhang","doi":"10.1002/mc.70032","DOIUrl":"10.1002/mc.70032","url":null,"abstract":"Autophagy plays a multifaceted role in tumorigenesis. However, the association between genetic variants in autophagy and gastric cancer susceptibility remains unclear. We evaluated the association between single-nucleotide polymorphisms (SNPs) of autophagy-related genes and gastric cancer risk using a cohort of 1,625 cases and 2,100 controls. Next, transcriptomic data were used to analyze differential gene expression and characterize the tumor immune microenvironment (TME). Single-cell RNA sequencing analysis was performed to investigate cell-type-specific expression profiles. In vitro gain/loss-of-function experiments were conducted to explore the biological roles of TRAF6 in cancer cells. We found that TRAF6 rs5030437 G > A conferred an increased risk of gastric cancer (OR = 1.23, 95% CI: 1.06-1.43, p = 1.28 × 10-3), particularly in males (OR = 1.24, 95% CI: 1.07-1.44, p = 3.69 × 10-3) and older individuals (OR = 1.41, 95% CI: 1.18-1.68, p = 1.53 × 10-4). TRAF6 expression was significantly upregulated in tumor tissues, correlating with poor prognosis in gastric cancer patients. Enrichment analyses implicated TRAF6 in immune response and inflammation signaling, manifested as its characteristic cellular expression distribution and influence on the abundance of specific immune cells. In vitro experiments demonstrated that TRAF6 positively regulated autophagy activity and promoted cell viability, migration, and proliferation of gastric cancer cells, which were reversed by autophagy inhibition. This study elucidated the genetic association of rs5030437 G > A and gastric cancer as well as the impacts of TRAF6 on TME dynamics and cancer biology, which provided novel insights into gastric carcinogenesis and the tumor ecosystem.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883242","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

Elevated Polyamine Metabolism Activates Fibroblasts via GCN2 Activation and Generates Senescent Fibroblasts to Promote Tumor Formation and Progression. 多胺代谢升高通过GCN2激活成纤维细胞，产生衰老成纤维细胞，促进肿瘤的形成和进展。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-19 DOI: 10.1002/mc.70034

Eric T Alexander, Katherine S Barone, Susan K Gilmour

{"title":"Elevated Polyamine Metabolism Activates Fibroblasts via GCN2 Activation and Generates Senescent Fibroblasts to Promote Tumor Formation and Progression.","authors":"Eric T Alexander, Katherine S Barone, Susan K Gilmour","doi":"10.1002/mc.70034","DOIUrl":"10.1002/mc.70034","url":null,"abstract":"GCN2 is one of the main sensors of amino acid starvation stress, and its activation in the stressful tumor microenvironment plays a crucial role in tumor survival. We hypothesized that elevated polyamine biosynthesis and subsequent depletion of precursor arginine in the tissue microenvironment activates GCN2 and alters stromal cell metabolism to support tumor cell survival and drive myeloid immunosuppressive function. To study the effect of elevated polyamine metabolism on fibroblast activation, we used the K6/ODC transgenic model of carcinogen-initiated, polyamine-promoted skin carcinogenesis. GCN2 loss significantly delayed tumor development and decreased tumor number and tumor burden in K6/ODC; GCN2-/- mice compared that in K6/ODC mice. Underlying dermal fibroblasts from nontumor bearing K6/ODC mice express elevated levels of genes associated with GCN2 activation and fibroblast activation. Expression of these genes was not elevated in K6/ODC; GCN2-/- dermis. In addition, K6/ODC mice have significantly more myeloid derived suppressor cells (MDSC) compared to normal littermates, and MDSCs were decreased in K6/ODC mice deficient in GCN2. Dermal fibroblasts cultured from K6/ODC transgenic mouse skin secrete increased levels of protumorigenic factors including senescence associated secretory phenotype (SASP) factors that stimulate invasiveness of stem-like epidermal tumorspheres as well as the polarization of M2-like macrophages. Using K6/ODC; p16-3MR mice in which senescent fibroblasts can be eliminated with ganciclovir treatment, carcinogen-initiated tumor development was greatly inhibited when senescent fibroblasts were eliminated in K6/ODC; p16-3MR mice. Our studies suggest a new paradigm in which cellular stress responses resulting from increased polyamine biosynthesis accelerate fibroblast activation and a senescence phenotype to create a protumorigenic microenvironment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883238","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

Uncovering the Role of DNA Repair Impairment in UVA-Induced Mutagenesis in Human Xeroderma Pigmentosum Variant Cells. 揭示DNA修复损伤在uva诱导的人类色素干皮变异型细胞突变中的作用。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-08-12 DOI: 10.1002/mc.70028

Camila Corradi, Natália Cestari Moreno, Nathalia Quintero-Ruiz, Giovana da Silva Leandro, Marcela Teatin Latancia, Tiago Antonio de Souza, Veridiana Munford, Carlos Frederico Martins Menck

{"title":"Uncovering the Role of DNA Repair Impairment in UVA-Induced Mutagenesis in Human Xeroderma Pigmentosum Variant Cells.","authors":"Camila Corradi, Natália Cestari Moreno, Nathalia Quintero-Ruiz, Giovana da Silva Leandro, Marcela Teatin Latancia, Tiago Antonio de Souza, Veridiana Munford, Carlos Frederico Martins Menck","doi":"10.1002/mc.70028","DOIUrl":"https://doi.org/10.1002/mc.70028","url":null,"abstract":"Ultraviolet A (UVA) radiation induces DNA damage both directly, by forming cyclobutane pyrimidine dimers (CPDs), and indirectly, by generating oxidative stress. Cells rely on nucleotide excision repair (NER) and translesion synthesis (TLS) to tolerate these lesions. Xeroderma pigmentosum variant (XP-V) cells, deficient in DNA polymerase eta (pol eta), exhibit a heightened risk of skin cancer due to impaired TLS. While XP-V patients are considered NER-proficient, our findings challenge this assumption by demonstrating that UVA-induced oxidative stress impaired NER activity, leading to increased C > T transitions at CPD sites. Whole-exome sequencing of UVA-irradiated XP-V cells revealed a substantial rise in mutations, with a distinct C > T signature characteristic of defective CPD repair. Notably, pretreatment with the antioxidant N-acetylcysteine (NAC) mitigated this effect, reducing C > T transitions through enhanced NER function and decreasing C > A transversions via its antioxidant properties. These results redefine the mutagenic landscape of XP-V cells, revealing that oxidatively generated damage to NER proteins-rather than TLS deficiency alone-contributes to their elevated mutation burden. Our findings suggest that antioxidant strategies may partially protect XP-V patients from UVA-driven mutagenesis enhancing the cells' DNA repair capacity, ultimately reducing skin cancer and contributing to better overall health outcomes.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822112","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