Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis最新文献

{"title":"FOXA2 promotes glutamine metabolism to facilitate the malignant development of bladder cancer by transcriptionally increasing GLS1 expression","authors":"Quan Yuan ,&nbsp;Bowen Liu ,&nbsp;Wei Yan ,&nbsp;Huifeng Li ,&nbsp;Jinxian Pu","doi":"10.1016/j.mrfmmm.2025.111920","DOIUrl":"10.1016/j.mrfmmm.2025.111920","url":null,"abstract":"<div><h3>Background</h3><div>Forkhead box A2 (FOXA2) is found to be abnormally overexpressed in bladder cancer (BCa), but its role and underlying molecular mechanisms in BCa progression remain revealed.</div></div><div><h3>Methods</h3><div>The expression levels of FOXA2, glutaminase 1 (GLS1), glutamine metabolism-related markers were examined using qRT-PCR and western blot. Glutamine metabolism was assessed by detecting glutamine uptake, intracellular glutamate, ATP, GSH and ROS levels. BCa cell proliferation, migration and invasion were analyzed by CCK8 assay, EdU assay, wound healing assay, and Transwell assay. The regulation of FOXA2 on GLS1 promoter was confirmed by dual-luciferase reporter assay and ChIP assay. Mice xenograft tumor models were constructed to evaluate the role of FOXA2 in BCa tumorigenesis.</div></div><div><h3>Results</h3><div>FOXA2 expression was upregulated in BCa cells and its knockdown significantly decreased GLS1 expression. Silencing of FOXA2 inhibited BCa cell glutamine metabolism, thus suppressing cell proliferation and metastasis, and these effects were reversed by GLS1 overexpression. In terms of mechanism, FOXA2 increased the transcription and expression of GLS1 by binding to its promoter region. Animal study revealed that FOXA2 interference also reduced BCa tumorigenesis through decreasing GLS1 expression.</div></div><div><h3>Conclusion</h3><div>FOXA2 accelerated BCa cell proliferation and metastasis by promoting GLS1-mediated glutamine metabolism, providing a novel therapy target for BCa.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111920"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145608072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DGKβ accelerates the progression of cervical cancer through ANGPT4-mediated tumor angiogenesis","authors":"Qing Li,&nbsp;Zhenyu Zhou,&nbsp;Xiaoying Li,&nbsp;Qiongyu Lan","doi":"10.1016/j.mrfmmm.2025.111913","DOIUrl":"10.1016/j.mrfmmm.2025.111913","url":null,"abstract":"<div><h3>Background</h3><div>Cervical cancer (CC) is a major cause of morbidity and mortality in women, with complex etiology and progression. Diacylglycerol kinases (DGKs) are pivotal in lipid metabolism. Although diacylglycerol kinase beta (DGKβ) is well-studied in neurology, its role in cancer, especially CC, remains underexplored. This study aimed to explore DGKβ's role and mechanism in CC.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis was employed to identify genes differentially expressed in CC, with western blot confirming DGKβ expression in CC cells. The role of DGKβ was examined through small interfering RNA-mediated gene silencing, proliferation tests, migration and invasion assays, and angiogenesis studies. In-depth bioinformatics explored DGKβ-regulated downstream targets and pathways. Pathological assessment elucidated the impact of DGKβ and angiopoietin 4 (ANGPT4) on CC samples.</div></div><div><h3>Results</h3><div>Our data identified DGKβ as a promising candidate gene in the context of CC. This conclusion stemmed from the notable observation that DGKβ exhibited a heightened expression in CC cell lines. Notably, the silencing of DGKβ resulted in the suppression of CC cell proliferation, invasion, migration, as well as the epithelial-mesenchymal transition processes. Additional bioinformatics analysis delving into DGKβ-associated genes revealed ANGPT4 as a downstream target gene of DGKβ, which is capable of modulating angiogenesis and possesses multiple cellular functions related to cell survival, proliferation, and migration. Most significantly, our findings also demonstrated that both DGKβ and ANGPT4 were overexpressed in clinical specimens of CC.</div></div><div><h3>Conclusion</h3><div>This study uncovered an oncogenic role for DGKβ in CC and identified a potential regulatory link between DGKβ and ANGPT4 in tumor angiogenesis. These findings provided promising directions for developing new diagnostic and therapeutic approaches for CC.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111913"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WTAP-mediated m6A modification of ARG2 mRNA Inhibits Its expression and drives prostate cancer malignant progression","authors":"Jianxin Li ,&nbsp;Yu Zheng ,&nbsp;Chaojiang Chen ,&nbsp;Zhuoyuan Lin ,&nbsp;Jiangang Pan ,&nbsp;Funeng Jiang ,&nbsp;Weide Zhong","doi":"10.1016/j.mrfmmm.2025.111912","DOIUrl":"10.1016/j.mrfmmm.2025.111912","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PCa) incidence increases as age advances and seriously endangers men’s health worldwide. Arginase 2 (ARG2) has been identified as a potential diagnostic and prognostic marker for PCa. However, the molecular mechanisms underlying its function in PCa remain undefined.</div></div><div><h3>Methods</h3><div>ARG2 mRNA and protein expression were quantified in PCa tissues and cells using qRT-PCR and Western blot. Cellular proliferation, glucose consumption, lactate production, apoptosis, and ferroptosis were evaluated via EdU incorporation, colony formation assays, commercial kits, and flow cytometry. Subsequently, the xenograft model was established to assess ARG2’s role in tumor growth <em>in vivo</em>. Bioinformatics analysis and RNA immunoprecipitation (RIP) were employed to investigate the interaction between Wilms’ tumor 1-associating protein (WTAP), a key component of the N6-methyladenosine (m6A) methyltransferase complex, and ARG2 mRNA. Besides, mRNA stability was determined using actinomycin D chase assays.</div></div><div><h3>Results</h3><div>ARG2 exhibited low expression in PCa tissues and cells. Upregulation of ARG2 inhibited proliferation and glycolysis, and promoted apoptosis, oxidative stress and ferroptosis of PCa cells. However, silencing ARG2 had the opposite effects. I<em>n vivo</em>, ARG2 overexpression suppressed tumor growth. Mechanistically, WTAP bound directly to ARG2 mRNA, and their expression levels were inversely correlated. WTAP knockdown phenocopied ARG2 overexpression by repressing proliferation and glycolysis and enhancing apoptosis/ferroptosis, effects reversed by ARG2 silencing. ARG2 overexpression counteracted the oncogenic effects of WTAP overexpression.</div></div><div><h3>Conclusion</h3><div>WTAP bound to ARG2 and suppressed its expression, thereby promoting the malignant progression of PCa.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111912"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated artificial mutagenesis of Bradyrhizobium diazoefficiens by gamma irradiation accelerates the acquisition of high-temperature tolerance","authors":"Yoshihiro Hase,&nbsp;Ikuko Nagafune,&nbsp;Katsuya Satoh","doi":"10.1016/j.mrfmmm.2025.111919","DOIUrl":"10.1016/j.mrfmmm.2025.111919","url":null,"abstract":"<div><div>Effective mutant screening is critical for improving industrial microorganisms. This study was conducted to evaluate the effect of repeated mutagenesis with gamma rays on the experimental evolution of rhizobial high-temperature tolerance. Wild-type <em>Bradyrhizobium diazoefficiens</em> USDA110 cells grow optimally at 32−34 °C, but their growth is markedly retarded at 36 °C. Wild-type cells were subcultured in a 96-well deep-well plate for 76 or 83 days, with a gradual increase in temperature from 34.0 to 37.0 °C. Additionally, they were exposed to gamma radiation (1–120 Gy, 10 times in total) during the experimental period. The 40-Gy and 80-Gy treatments generated the most lines with high-temperature-tolerance. However, after extended subculturing without mutagenesis, tolerant lines obtained following the 80-Gy treatment produced smaller colonies than tolerant lines obtained after the 40-Gy treatment, suggesting the accumulation of deleterious mutations. These results imply that approximately 40 Gy is the appropriate dose for accumulating beneficial mutations under our experimental conditions. The two most tolerant lines obtained via the 30-Gy treatment commonly had a mutation in the 16S ribosomal RNA gene and the DNA-directed RNA polymerase subunit beta′ gene (<em>rpoC</em>), possibly reflecting a strong relationship with high-temperature tolerance. The optimal mutagenesis conditions for accumulating beneficial mutations were discussed based on the number of induced mutations in the population.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111919"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145608075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Saikosaponin-d Mediates FOXG1 to Reverse Docetaxel Resistance in Prostate Cancer through Oxidative Phosphorylation” [Mut. Res. - Fundam. Mol. Mech. Mutagenesis 829 (2024) 111875]","authors":"Jun Meng,&nbsp;Bo Yang,&nbsp;Chang Shu,&nbsp;Shuai Jiang","doi":"10.1016/j.mrfmmm.2025.111914","DOIUrl":"10.1016/j.mrfmmm.2025.111914","url":null,"abstract":"","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111914"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CPMFD: An algorithm for Classification of Point Mutations together with Frameshift Determination in related mRNA sequences","authors":"Probir Mondal ,&nbsp;Pratyay Banerjee ,&nbsp;Krishnendu Basuli","doi":"10.1016/j.mrfmmm.2025.111918","DOIUrl":"10.1016/j.mrfmmm.2025.111918","url":null,"abstract":"<div><div>Mutations are responsible for the genetic origin of various diseases. Existing techniques for mutation identification often fails to detect the full spectrum of mutations in complex genomes hindering progress in diagnosis, treatment and prevention of diseases. Here we propose an algorithm to identify the location and type of mutation occurring in a mutated string with respect to a reference mRNA sequence. In addition to identifying insertion and deletion, by constructing suitable rational combinations of the prime numbers, our algorithm is able to classify point mutations in a novel way by distinguishing missense mutation from silent mutation. Amino acid transformation at each missense mutation site is identified. Moreover, the method allows to locate regions in the sequence undergoing frameshift. It turns out to be efficient when applied on sample dataset. Application of this framework to two haplotypes of the <em>Plasmodium falciparum</em> datasets exhibits different mutation profile to develop similar chloroquine resistance. Despite the overwhelming similarity between the <span><math><mi>β</mi></math></span>-globin genes of pygmy and common chimpanzees, our algorithm is able to pinpoint the minute details of the mutations occurring in them differentiating the two species. Additionally, in Alzheimer datasets, the method meticulously identifies true variations in related genes.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111918"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145544548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-induced HIF-1α enhanced the tumorigenesis in non-small cell lung cancer by targeting GAB2","authors":"Xunxia Zhu ,&nbsp;Xiaoyong Shen ,&nbsp;Xiaoyu Chen,&nbsp;Xuelin Zhang,&nbsp;Wen Gao","doi":"10.1016/j.mrfmmm.2025.111917","DOIUrl":"10.1016/j.mrfmmm.2025.111917","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is a lethal disease with high morbidity and mortality rates. HIF-1α is confirmed to be involved in NSCLC. However, the detailed mechanism of its role remains unclear. NCI-H226 and SK-MES-1 cell lines were used to explore the mechanisms by which hypoxia affects the progression of NSCLC <em>in vitro</em>. The cellular functions were detected by transwell. The expressions of key biomarkers were examined by Real-time quantitative reverse transcription PCR (qRT-PCR) and Western Blot assays. The RNA sequencing analysis was used to explore the downstream targets of HIF-1α. Luciferase and Chromatin immunoprecipitation (ChIP) assays confirmed the interaction between HIF-1α and GAB2. What’s more, the xenograft model was used to investigate the effect of GAB2 <em>in vivo</em>. Hypoxia promoted the migration and invasion capabilities of NCI-H226 and SK-MES-1 cells. RNA sequencing analysis revealed that the expression of GAB2 is dramatically altered under a hypoxic environment. The bioinformatics analysis implied that the differentially expressed genes (DEGs) were enriched in the MEK/ERK signaling pathway and the significantly expressed GAB2 was associated with HIF-1α. Functionally, GAB2 regulated migration and invasion capabilities in vitro and facilitated tumor growth and lung metastasis of NSCLC <em>in vivo</em>. What’s more, luciferase and ChIP assays further demonstrated that HIF-1α could bind to GAB2<strong>.</strong> Hypoxia-induced HIF-1α enhanced tumor growth and lung metastasis in NSCLC by targeting GAB2, which might provide novel insights into GAB2 as a potential therapeutic target for NSCLC.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111917"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL14-mediated m6A modification of ETV4 inhibits tumor development in colorectal cancer","authors":"Xiaofeng Liao,&nbsp;Tao Hu","doi":"10.1016/j.mrfmmm.2025.111910","DOIUrl":"10.1016/j.mrfmmm.2025.111910","url":null,"abstract":"<div><h3>Background</h3><div>Many m6A methyltransferases have been identified to regulate colorectal cancer (CRC) progression. METTL14 has been confirmed to play a negative role in CRC process, but the molecular mechanism of METTL14 in regulating CRC progression needs to be further elucidated.</div></div><div><h3>Methods</h3><div>The levels of METTL14, YTHDF2 and ETS translocation variant 4 (ETV4) were examined by qRT-PCR and western blot. Cell proliferation and apoptosis were determined by colony formation assay and flow cytometry. Cell glycolysis was assessed by detecting corresponding indicators. Cell ferroptosis was evaluated via measuring SOD, MDA, GSH, ROS and Fe^2 + levels. The interaction between ETV4 and METTL14 or m6A readers was confirmed by RIP assay and RNA pull-down assay. Animal experiments were performed to confirm METTL14 roles <em>in vivo</em>.</div></div><div><h3>Results</h3><div>METTL14 was downregulated in CRC tissues and cells, which overexpression inhibited proliferation and glycolysis, as well as promoted apoptosis and ferroptosis in CRC cells. METTL14 reduced the mRNA stability of ETV4 and inhibited ETV4 protein expression through m6A modification. m6A reader YTHDF2 could recognize m6A-methylated ETV4. The downregulation of ETV4 by METTL14 leads to increased apoptosis and ferroptosis in CRC cells, suggesting a critical role in tumor suppression. Moreover, METTL14 inhibited CRC tumorigenesis <em>in vivo</em> via reducing ETV4 expression.</div></div><div><h3>Conclusion</h3><div>METTL14 accelerated CRC cell apoptosis and ferroptosis via downregulating ETV4 in m6A-dependent manner, providing a molecular target for CRC treatment.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111910"},"PeriodicalIF":1.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of TERT promoter hotspot mutations using droplet digital PCR in hepatoblastoma and hepatocellular carcinoma","authors":"Yoko Hiyama ,&nbsp;Masato Kojima ,&nbsp;Sho Kurihara ,&nbsp;Isamu Saeki ,&nbsp;Ryo Touge ,&nbsp;Takahiro Fukazawa ,&nbsp;Takanori Harada ,&nbsp;Eiso Hiyama","doi":"10.1016/j.mrfmmm.2025.111915","DOIUrl":"10.1016/j.mrfmmm.2025.111915","url":null,"abstract":"<div><div>Somatic mutations in the telomerase reverse transcriptase promoter (<em>TERT</em>p) region are common in many cancers, including in liver cancers. Detection of <em>TERT</em>p mutations in tumor tissue DNAs and cell-free tumor DNAs is useful for diagnosing and monitoring cancers. Since the most common <em>TERT</em>p hotspot mutations, C228T and C250T, are difficult to identify using Sanger sequencing, we tested an easy and highly sensitive alternative method that targets these two sites using droplet digital PCR. Using this method, both the sensitivity and specificity for detecting these two mutations were 100 % in DNA samples derived from cell lines and liver cancer tissues, including hepatocellular carcinoma (HCC) and hepatoblastoma (HB). The detection limit for the allele frequencies of these mutations was approximately 0.1 %. This method is also widely applicable; for instance, it can be applied to DNA derived from FFPE (formalin-fixed paraffin embedded) samples. In addition, we applied this method to detecting <em>TERT</em>p mutations in cell-free DNA samples of patients with <em>TERT</em>p-mutated tumors. Finally, we found that outcomes for HB patients with <em>TERT</em>p mutations were significantly worse than in those without mutations, indicating the importance of this method for improving patient outcomes. In light of this, we discuss the advantages of this method for clinical implementation in the detection and monitoring of cancers.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111915"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting cancer-cell mitochondria using Tigecycline improves radiotherapy response in colorectal cancer cell line","authors":"Sepideh Hassanpour Khodaei ,&nbsp;Shahnaz Sabetkam ,&nbsp;Zeinab Mazloumi ,&nbsp;Khadijeh Dizaji Asl ,&nbsp;Ali Rafat","doi":"10.1016/j.mrfmmm.2025.111905","DOIUrl":"10.1016/j.mrfmmm.2025.111905","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer<span> (CRC) is the third most common cancer worldwide and causes more than 50,000 deaths in the United States each year. Due to the limited therapeutic options and poor prognosis in CRC, extensive research and development of novel therapeutic methods is essential. In this regard, the presence of cancer stem cells with unlimited division ability is the main reason for the therapeutic resistance in CRC. Tigecycline is a pharmacological mitochondria inhibitor and blocks mitochondria-related cell proliferation in cancer cells. This study investigated the effects of Tigecycline combined with radiotherapy on CRC cell apoptosis.</span></div></div><div><h3>Methods</h3><div>Human colorectal cancer cells (HCT-116) were treated with Tigecycline, and cell viability was measured with MTT assay. In the next step, the cells were exposed to radiation using a Siemens Primus 6 MV linear accelerator at radiation dose of 400 cGy. Finally, we evaluated cancer cell apoptosis, caspase-3 activity and apoptotic-related genes expression with AnnexinV/PI, flowcytometry and gene expression, respectively.</div></div><div><h3>Results</h3><div>The MTT assay revealed an IC50 value of 93 μM for Tigecycline after 48 hours. Mitochondria inhibition, at its IC50 value, sensitizes colorectal cancer cells to radiotherapy. Compared to monotherapy, the combination therapy increased the number of apoptotic cells and caspase-3 activity, up-regulated pro-apoptotic genes, and down-regulated anti-apoptotic genes.</div></div><div><h3>Conclusion</h3><div>In conclusion, our data suggests that targeting mitochondria may represent a clinically relevant approach to enhance the sensitivity of colorectal cancer cells to therapy. These findings could provide new insights into cancer therapy and might be used as a novel method to improve the current state of CRC therapy.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"831 ","pages":"Article 111905"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}