Acta biochimica et biophysica Sinica最新文献

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Lutonarin attenuates LPS-induced intestinal epithelial barrier dysfunction: a functional and transcriptomic analysis. Lutonarin减弱lps诱导的肠上皮屏障功能障碍:功能和转录组学分析。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-15 DOI: 10.3724/abbs.2025069
Qian Du, Jing Li, Guyanan Li, Zihan Wang, Siran Yu, Lihua Wang, Xiangyu Guo, Dali Wang, Bin Hui, Yuehua Tu, Wenguang Sun, Xuan Zhang, Wei Chen
{"title":"Lutonarin attenuates LPS-induced intestinal epithelial barrier dysfunction: a functional and transcriptomic analysis.","authors":"Qian Du, Jing Li, Guyanan Li, Zihan Wang, Siran Yu, Lihua Wang, Xiangyu Guo, Dali Wang, Bin Hui, Yuehua Tu, Wenguang Sun, Xuan Zhang, Wei Chen","doi":"10.3724/abbs.2025069","DOIUrl":"https://doi.org/10.3724/abbs.2025069","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zinc fingers are responsible for the efficient control of KLF7 on the transcription of genes in the NF-κB signaling pathway and fatty acid β-oxidation. 锌指有效控制KLF7对NF-κB信号通路和脂肪酸β-氧化相关基因的转录。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-14 DOI: 10.3724/abbs.2025053
Jiazhen Tian, Tingting Zhang, Zhaoxiong Qi, Yuechan Chen, Xiangquan Mi, Zhiwei Zhang
{"title":"Zinc fingers are responsible for the efficient control of KLF7 on the transcription of genes in the NF-κB signaling pathway and fatty acid β-oxidation.","authors":"Jiazhen Tian, Tingting Zhang, Zhaoxiong Qi, Yuechan Chen, Xiangquan Mi, Zhiwei Zhang","doi":"10.3724/abbs.2025053","DOIUrl":"https://doi.org/10.3724/abbs.2025053","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intracellular acetyl phosphate modulates Escherichia coli pyruvate metabolism. 胞内乙酰磷酸调节大肠杆菌丙酮酸代谢。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-14 DOI: 10.3724/abbs.2025068
Ling Zhang, Hongmei Shi, Zixiang Liu, Jing Gu, Jiaoyu Deng
{"title":"Intracellular acetyl phosphate modulates <i>Escherichia coli</i> pyruvate metabolism.","authors":"Ling Zhang, Hongmei Shi, Zixiang Liu, Jing Gu, Jiaoyu Deng","doi":"10.3724/abbs.2025068","DOIUrl":"https://doi.org/10.3724/abbs.2025068","url":null,"abstract":"<p><p>Lysine acetylation has been shown to be an abundant and vital post-translational modification (PTM) that utilizes acetyl phosphate (AcP) as one of the acetyl group donors in bacteria. The pyruvate dehydrogenase (PDH) complex catalyzes the conversion from pyruvate to acetyl coenzyme A (acetyl-CoA). Thus far, the connection between lysine acetylation and pyruvate metabolism has not been thoroughly investigated. In this study, we show that AcP could acetylate <i>Escherichia coli</i> pyruvate dehydrogenase (AceE) <i>in vitro</i> and <i>in vivo</i>, which could be reversed by protein lysine deacetylase (CobB). <i>In vitro</i> treatment of AceE with AcP also causes increased phosphorylation of the protein, whereas deleting <i>ackA</i> does not affect the phosphorylation of the protein. As a result, <i>in vitro</i> treatment of AceE by AcP leads to decreased enzymatic activity. In contrast, deleting <i>ackA</i> leads to increased acetylation and enzymatic activity of AceE, and deleting <i>pta</i> results in the decreased acetylation and enzymatic activity of AceE. As expected, deleting <i>pta</i> in <i>E</i>. <i>coli</i> causes pyruvate accumulation. Although deleting <i>ackA</i> also causes pyruvate accumulation, decreased expression of the two genes involved in pyruvate metabolism ( <i>ldhA</i> and <i>poxB</i>) is observed in the mutant, indicating that AcP could affect pyruvate metabolism by other routes in addition to modulating the AceE activity. Thus, our results demonstrate that intracellular AcP could modulate pyruvate metabolism in <i>E</i>. <i>coli</i>. For the first time, a linkage between AcP-mediated protein lysine acetylation, pyruvate dehydrogenase activity, and pyruvate metabolism is established.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to: Stattic sensitizes osteosarcoma cells to epidermal growth factor receptor inhibitors via blocking the interleukin 6-induced STAT3 pathway. statstatic通过阻断白细胞介素6诱导的STAT3通路使骨肉瘤细胞对表皮生长因子受体抑制剂敏感。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-13 DOI: 10.3724/abbs.2025079
Shenglin Wang, Yunqing Wang, Zhen Huang, Hongxiang Wei, Xinwen Wang, Rongkai Shen, Wenbin Lan, Guangxian Zhong, Jianhua Lin
{"title":"Corrigendum to: Stattic sensitizes osteosarcoma cells to epidermal growth factor receptor inhibitors via blocking the interleukin 6-induced STAT3 pathway.","authors":"Shenglin Wang, Yunqing Wang, Zhen Huang, Hongxiang Wei, Xinwen Wang, Rongkai Shen, Wenbin Lan, Guangxian Zhong, Jianhua Lin","doi":"10.3724/abbs.2025079","DOIUrl":"https://doi.org/10.3724/abbs.2025079","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Causal effects of immune cells on the efficacy and adverse drug reactions of platinum drugs. 免疫细胞对铂类药物疗效及不良反应的因果影响。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-06 DOI: 10.3724/abbs.2025052
Wanting Li, Bing Yu, Qi Xiao, Zhao Zhang, Hanxue Huang, Jiajia Cui, Guangying Qi, Jifang Zheng, Jiye Yin, Zhaoqian Liu, Xi Li, Howard L McLeod
{"title":"Causal effects of immune cells on the efficacy and adverse drug reactions of platinum drugs.","authors":"Wanting Li, Bing Yu, Qi Xiao, Zhao Zhang, Hanxue Huang, Jiajia Cui, Guangying Qi, Jifang Zheng, Jiye Yin, Zhaoqian Liu, Xi Li, Howard L McLeod","doi":"10.3724/abbs.2025052","DOIUrl":"https://doi.org/10.3724/abbs.2025052","url":null,"abstract":"<p><p>Platinum drugs are widely used in lung cancer chemotherapy, but the immune characteristics of different individuals have different effects on the sensitivity and side effects of platinum drugs. In this study, we use 731 kinds of immune cell traits of 3757 healthy individuals and 429 patients with non-small cell lung cancer (NSCLC) in Xiangya Hospital of Central South University to conduct a Mendel randomized analysis in order to find out the causal relationship between some immune cell traits and the efficacy and adverse reactions of platinum drugs. We find that CD19 on CD24 <sup>+</sup>CD27 <sup>+</sup> B cell (OR = 0.598, <i>P</i> = 0.004) is the most significant immune cell trait as the protective factor of efficacy. HLA-DR <sup>+</sup>CD8 <sup>+</sup> T cell % lymphocyte (OR = 0.427, <i>P</i> = 7.55 × 10 <sup>-4</sup>) and HLA-DR <sup>+</sup>CD8 <sup>+</sup> T cell % T cell (OR = 0.471, <i>P</i> = 0.003) are the protective factors of liver injury. CD39 on CD39 <sup>+</sup> secreting CD4 <sup>+</sup> regulatory T cell (OR = 28.729, <i>P</i> = 0.009) and CD3 on CD39 <sup>+</sup> resting CD4 regulatory T cell (OR = 3.024, <i>P</i> = 0.009) are the risk factors of renal injury. Meanwhile, B cell-related traits mainly affect gastrointestinal upset and cutaneous toxicity, while T cell-related traits mainly affect other outcome variables. These findings may promote our understanding of the relationship between the efficacy and adverse reactions of platinum drugs and the immune system, and promote future development of biomarkers for predicting the efficacy and adverse reactions of platinum drugs.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Osteocalcin carboxylation/undercarboxylation levels and gene variants associated with type 2 diabetes mellitus in the Chinese Han population. 中国汉族2型糖尿病相关骨钙素羧化/欠羧化水平和基因变异
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-04-30 DOI: 10.3724/abbs.2025060
Luyue Qi, Hong Wu, Xiangqi Li, Yang Xu, Liangyong Liu
{"title":"Osteocalcin carboxylation/undercarboxylation levels and gene variants associated with type 2 diabetes mellitus in the Chinese Han population.","authors":"Luyue Qi, Hong Wu, Xiangqi Li, Yang Xu, Liangyong Liu","doi":"10.3724/abbs.2025060","DOIUrl":"https://doi.org/10.3724/abbs.2025060","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crystal structures of Kif2A complexed with WDR5 reveal the structural plasticity of WIN-S7 sites. Kif2A与WDR5配合的晶体结构揭示了WIN-S7位点的结构可塑性。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-04-30 DOI: 10.3724/abbs.2025066
Yang Yang, Shuting Zhang, Zhangyu Wu, Wenwen Li, Xuefang Sun, Yumi Xuan, Tianrong Hang, Li Xu, Xuemin Chen
{"title":"Crystal structures of Kif2A complexed with WDR5 reveal the structural plasticity of WIN-S7 sites.","authors":"Yang Yang, Shuting Zhang, Zhangyu Wu, Wenwen Li, Xuefang Sun, Yumi Xuan, Tianrong Hang, Li Xu, Xuemin Chen","doi":"10.3724/abbs.2025066","DOIUrl":"https://doi.org/10.3724/abbs.2025066","url":null,"abstract":"<p><p>Chromosome congression and spindle assembly are essential for genomic stability and proper cell division, with deficiencies in these processes linked to tumorigenesis. WD repeat-containing protein 5 (WDR5), a core component of the mixed lineage leukemia (MLL) methyltransferase complex, directly binds to kinesin family member 2A (Kif2A) to regulate these mitotic events. Despite the importance of this interaction, its structural basis for Kif2A recognition by WDR5 remains unclear. Here, we determine the crystal structure of WDR5 in complex with a Kif2A-derived peptide (residues 114-122) at a resolution of 1.85 Å. Structural analysis reveals that Kif2A engages both the WIN and S7 sites of WDR5 via Arg117 and Ser121, with Ser121 forming hydrogen bonds with WDR5 Tyr191 and Lys259, driving Tyr191 rotation and opening the S7 pocket. Additional structures of WDR5 complexed with truncated or mutated Kif2A peptides and a WDR5 Y191F variant highlight the dynamic nature of Tyr191. Notably, anti-WDR5 compounds exhibit a similar binding mode at the WDR5 WIN-S7 site. The results of mutagenesis combined with isothermal titration calorimetry (ITC) assays underscore the critical roles of Arg117 and Ser121 in mediating the binding of Kif2A to WDR5. In summary, our findings provide atomic-level insights into the molecular mechanisms underlying the non-canonical mitotic function of the MLL/WDR5 complex and highlight WIN-S7 sites as promising therapeutic targets for diseases associated with chromosomal instability, such as cancers.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New feature of hMEIOB and hSPATA22 binding to ssDNA from a single-molecule perspective. hMEIOB和hSPATA22与ssDNA单分子结合的新特征。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-04-28 DOI: 10.3724/abbs.2025057
Yating Xu, Wei Qu, Erchi Zhou, Qi Sun, Weihao Gong, Lei Xu, Yaoke Lei, Zhangying Jia, Hanqing Shi, Xinghua Zhang, Mengcheng Luo
{"title":"New feature of hMEIOB and hSPATA22 binding to ssDNA from a single-molecule perspective.","authors":"Yating Xu, Wei Qu, Erchi Zhou, Qi Sun, Weihao Gong, Lei Xu, Yaoke Lei, Zhangying Jia, Hanqing Shi, Xinghua Zhang, Mengcheng Luo","doi":"10.3724/abbs.2025057","DOIUrl":"https://doi.org/10.3724/abbs.2025057","url":null,"abstract":"<p><p>MEIOB and SPATA22 are gonad-specific proteins that function in meiosis recombination. Mutations in these two proteins cause oligospermia or azoospermia in human males. It has been reported that the heterodimer composed of MEIOB and SPATA22 recognizes and binds to the single-strand DNA (ssDNA) protected by the replication protein A (RPA) complex to promote DNA damage repair during homologous recombination. However, the amino acid sequences of the two proteins are inconsistent in humans and rodents, which leads to functional differences in meiosis. In this study, human-derived MEIOB (hMEIOB) and SPATA22 (hSPATA22) are expressed and purified for electrophoretic mobility shift assay (EMSA), magnetic tweezer (MT) assay and bio-layer interferometry (BLI) assay to analyze the ssDNA binding patterns. The results show that hMEIOB has low ssDNA-binding affinity and stability alone, but hSPATA22 binds to ssDNA faster and more stably and promotes ssDNA condensation. Strong binding affinity and stability to ssDNA are present when the hMEIOB-hSPATA22 heterodimer is formed. Moreover, we find that multiple hMEIOB-hSPATA22 heterodimers spontaneously aggregate <i>in vitro</i>. hRPA complex weakens the binding affinity of hMEIOB, hSPATA22 and hMEIOB-hSPATA22 heterodimer to ssDNA, and it can also bind to hSPATA22 and hMEIOB-hSPATA22 heterodimer <i>in vitro</i>, which might be related to the proven function of RPA complex to protect ssDNA and recruit proteins related to DNA damage repair during meiosis. Overall, this study is the first time to elucidate the binding patterns of the hMEIOB and hSPATA22 to ssDNA <i>in vitro</i>, and to verify the relationship between the RPA complex and meiosis-related proteins, MEIOB and SPATA22, from single-molecule perspective.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
D-CAPS: an efficient CRISPR-Cas9-based phage defense system for E. coli. D-CAPS:高效的基于crispr - cas9的大肠杆菌噬菌体防御系统
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-04-28 DOI: 10.3724/abbs.2024208
Mingjun Sun, Jie Gao, Hongjie Tang, Hengyi Wang, Liyan Zhou, Chuan Song, Yongqiang Tian, Qi Li
{"title":"D-CAPS: an efficient CRISPR-Cas9-based phage defense system for <i>E</i>. <i>coli</i>.","authors":"Mingjun Sun, Jie Gao, Hongjie Tang, Hengyi Wang, Liyan Zhou, Chuan Song, Yongqiang Tian, Qi Li","doi":"10.3724/abbs.2024208","DOIUrl":"https://doi.org/10.3724/abbs.2024208","url":null,"abstract":"<p><p><i>Escherichia coli</i> is widely used in industrial chemical synthesis but faces significant challenges due to bacteriophage contamination, which reduces product quality and yield. Therefore, developing an efficient antiphage system is essential. In this study, we develop a CRISPR-Cas9-based antiphage system (CAPS) targeting essential genes of the T7 phage (gene <i>5</i> and gene <i>19</i>) with single gRNAs transformed into MG1655 strains expressing Cas9. While CAPS provides limited resistance, with plating efficiencies ranging from 10 <sup>-5</sup> to 10 <sup>-1</sup>, further optimization is needed. To enhance efficacy, we design a double-site-targeting CRISPR-Cas9-based antiphage system (D-CAPS). D-CAPS demonstrates complete resistance, with no plaques observed even at a high multiplicity of infection (MOI of 2), and growth curve analysis reveals that antiphage <i>E</i>. <i>coli</i> strains grow normally, similar to the wild-type strain, even at a high multiplicity of infection. Furthermore, D-CAPS is effective against BL21(DE3) strains, showing strong resistance and demonstrating its versatility across different <i>E</i> . <i>coli</i> strains. Protein expression analysis via green fluorescent protein confirms that <i>E</i>. <i>coli</i> carrying D-CAPS could maintain normal protein expression levels even in the presence of phages, comparable to wild-type strains. Overall, D-CAPS offers a robust and versatile approach to enhancing <i>E</i>. <i>coli</i> resistance to phages, providing a practical solution for protecting industrial <i>E</i>. <i>coli</i> strains and improving fermentation processes.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GWAS study of myelosuppression among NSCLC patients receiving platinum-based combination chemotherapy. 接受铂类联合化疗的NSCLC患者骨髓抑制的GWAS研究。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-04-28 DOI: 10.3724/abbs.2025013
Hanxue Huang, Junyan Liu, Qi Xiao, Chenxue Mao, Lei She, Lulu Yu, Bing Yu, Mengrong Lei, Ying Gao, Baimei He, Pinhua Pan, Xi Li, Jiye Yin, Zhaoqian Liu
{"title":"GWAS study of myelosuppression among NSCLC patients receiving platinum-based combination chemotherapy.","authors":"Hanxue Huang, Junyan Liu, Qi Xiao, Chenxue Mao, Lei She, Lulu Yu, Bing Yu, Mengrong Lei, Ying Gao, Baimei He, Pinhua Pan, Xi Li, Jiye Yin, Zhaoqian Liu","doi":"10.3724/abbs.2025013","DOIUrl":"https://doi.org/10.3724/abbs.2025013","url":null,"abstract":"<p><p>Platinum-based chemotherapy remains the mainstay for non-small cell lung cancer (NSCLC), but it frequently causes dose-limiting myelosuppression, with significant individual variability in susceptibility. However, the genetic basis of myelosuppression side effects remains elusive, greatly hindering personalized therapeutic approaches. In this study, we perform a comprehensive genome-wide association analysis on 491 NSCLC patients receiving platinum-based chemotherapy, examining 4,690,998 single-nucleotide polymorphisms (SNPs) to identify relevant genetic variants. LDBlockShow, FUMA, and MAGMA are utilized to explore linkage disequilibrium, expression quantitative trait loci (eQTLs), chromatin interaction, and conduct gene-based and gene set-based analysis of candidate SNPs. The GWAS results reveal that rs6856089 and its linked SNPs are significantly associated with platinum-based chemotherapy-induced myelosuppression. Specifically, patients with the A allele of rs6856089 have a significantly lower risk of myelosuppression (odds ratio (OR) = 0.1300, <i>P</i> = 7.59 × 10 <sup>-8</sup>). Furthermore, gene-based analysis reveals that <i>EMCN</i> ( <i>P</i> = 2.47 × 10 <sup>-5</sup>), which encodes endomucin, a marker for hematopoietic stem cells, might mediate myelosuppression. This study provides a scientific basis for the individual differences in platinum-based chemotherapy-induced myelosuppression.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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