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}
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}
Fen Tan, Juan Chen, Lunquan Sun, Lu Zhang, Rui Zhou
{"title":"Cx58 is associated with the metastasis of non-small cell lung cancer via MEF2B/Cx58 axis.","authors":"Fen Tan, Juan Chen, Lunquan Sun, Lu Zhang, Rui Zhou","doi":"10.3724/abbs.2025049","DOIUrl":"https://doi.org/10.3724/abbs.2025049","url":null,"abstract":"<p><p>Connexins (Cxs), also known as gap junction proteins, are structurally related transmembrane proteins and have been implicated in carcinogenesis. Although some evidence suggests that these proteins are tumor suppressors due to their reduced expression in cancers, recent research indicates their complicated roles in tumor progression during different stages, including metastasis. Here, we show that Cx58, which is upregulated in non-small cell lung cancer (NSCLC), is modulated by myocyte-enhancer binding factor 2B (MEF2B). Either <i>Cx58</i> or <i>MEF2B</i> knockdown attenuates the migration and invasion of NSCLC cells by inducing cytoskeleton rearrangement. Additionally, the prometastatic role of Cx58 in NSCLC is demonstrated <i>in vivo</i>. In conclusion, our findings suggest that Cx58 is transcriptionally activated by MEF2B and is involved in the metastasis of NSCLC by regulating cytoskeleton organization. Targeting the MEF2B/Cx58 axis may be exploited as a modality for improving NSCLC therapy.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956427","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}
{"title":"Single-cell transcriptomic data reveal the cellular heterogeneity of glutamine metabolism in gastric premalignant lesions and early gastric cancer.","authors":"Qingfeng Ni, Jiawei Yu, Yuanjie Niu, Zhenwei Han, Boyang Hu, Yang Wang, Jianwei Zhu","doi":"10.3724/abbs.2025061","DOIUrl":"https://doi.org/10.3724/abbs.2025061","url":null,"abstract":"<p><p>Glutamine metabolism is a hallmark of cancer metabolism. This study aims to perform a comprehensive and systematic single-cell profile of glutamine metabolism in premalignant and malignant gastric lesions. We use single-cell transcriptomics data from chronic atrophic gastritis (CAG) and early gastric cancer (EGC) lesions and investigate glutamine metabolism features at the single-cell level. Experiments are implemented to validate the expression and biological role of ERO1LB in gastric cancer (GC). A single-cell atlas based on 22511 cells from premalignant and early-malignant gastric lesions is established. Among these cells, epithelial cells constitute the dominant cell population in both CAG and EGC lesions. The activity of glutamine metabolism is higher in epithelial cells from EGC lesions than in those from CAG lesions. Among the epithelial cell subpopulations, glutamine metabolism is more active in the epithelial cell subpopulation cluster_4 in EGCs than in CAG lesions. As a key marker gene of this subpopulation, <i>ERO1LB</i> is experimentally proven to be overexpressed in human GC tissue lesions. In both <i>in vitro</i> and <i>in vivo</i> experiments, overexpression of ERO1LB in GC cells increases glutamine metabolism, facilitates cell growth and migration and prevents cell apoptosis, and vice versa. This study provides insight into the cellular heterogeneityof glutamine metabolism within the gastric mucosa in premalignant and malignant gastric lesions and identifies ERO1LB as a key orchestrator of glutamine metabolism, which may help to identify markers for GC prevention and contribute to our understanding of GC pathogenesis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956808","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}
{"title":"Long noncoding RNA UCA1 knockdown inhibits cisplatin-resistant cervical cancer tumorigenesis via the miR-195-5p/IKBKB axis.","authors":"Bi Wang, Ling Li, Zhengyu Wu, Xuanzhen Qian, Wenfeng Yu, Zhi Huang","doi":"10.3724/abbs.2025032","DOIUrl":"https://doi.org/10.3724/abbs.2025032","url":null,"abstract":"<p><p>Cisplatin resistance is a major cause of poor prognosis in patients with cervical cancer. Dysregulation of long noncoding RNAs (lncRNAs) plays a key role in chemoresistance. Our results reveal that the lncRNA UCA1 is upregulated in cisplatin (DDP)-resistant cervical cancer tissues and HeLa cells. Mechanistically, the lncRNA UCA1 acts as a sponge for miR-195-5p, targeting IKBKB. UCA1 enhances proliferation, migration, and invasion while reducing apoptosis in DDP-resistant HeLa cells via the miR-195-5p/IKBKB axis. Additionally, UCA1 upregulates BNIP3Δex2 and p-p65 expressions and downregulates BNIP3 expression in DDP-resistant HeLa cells. Abnormal expressions of BNIP3Δex2 and BNIP3 significantly alter the malignant progression of HeLa/DPP cells. <i>In vivo</i>, <i>UCA1</i> silencing inhibits growth, enhances apoptosis, and upregulates IKBKB, BNIP3Δex2, and p-p65 expressions while downregulating BNIP3 expression in subcutaneous xenografts in nude mice by targeting miR-195-5p. Overall, this study highlights a novel promising target for the treatment of DDP-resistant cervical cancer.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957407","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}
Yu Du, Xinchao Zhang, Yixin Xu, Yuefan Zhou, Yanping Xu
{"title":"D-mannose suppresses the angiogenesis and progression of colorectal cancer.","authors":"Yu Du, Xinchao Zhang, Yixin Xu, Yuefan Zhou, Yanping Xu","doi":"10.3724/abbs.2025043","DOIUrl":"https://doi.org/10.3724/abbs.2025043","url":null,"abstract":"<p><p>Angiogenesis is an important factor influencing the development of solid tumors, and vascular endothelial growth factor receptor-2 (VEGFR2) is a central regulator of angiogenesis. Antibodies and inhibitors against VEGFR2 have been widely used in various malignancies. However, the regulatory mechanism of VEGFR2 has not been fully clarified. Here, we show that D-mannose can significantly inhibit angiogenesis and tumor growth by degrading VEGFR2. Specifically, D-mannose inactivates GSK3β by promoting the phosphorylation of GSK3β at Ser9, enhances the nuclear translocation of TFE3, and promotes lysosomal biogenesis, thereby increasing the lysosome-mediated degradation of VEGFR2. Thus, D-mannose significantly inhibits the proliferation, migration, and capillary formation of human umbilical vein endothelial cells (HUVECs) <i>in vitro</i>. Oral administration of D-mannose dramatically inhibits angiogenesis and tumor growth in mice. Our findings reveal a previously unrecognized anti-tumor mechanism of D-mannose by destabilizing VEGFR2 and provide a new strategy for the clinical treatment of colorectal cancer (CRC).</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958396","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}
{"title":"Integrated quantitative proteomics and phosphoproteomics analysis reveals USP46-POU4F1-HPSE signaling axis in the pathogenesis of Hirschsprung disease.","authors":"Guowei Li, Fengyin Sun, Jiawei Chen, Qiongqian Xu, Xintao Zhang, Luqiu Chen, Peimin Hou, Aiwu Li","doi":"10.3724/abbs.2025064","DOIUrl":"https://doi.org/10.3724/abbs.2025064","url":null,"abstract":"<p><p>Hirschsprung's disease (HSCR) is a congenital disorder characterized by the absence of enteric ganglion cells in the distal colon, resulting in functional intestinal obstruction. While genetic mutations and microenvironmental imbalances have been implicated in HSCR, the underlying molecular mechanisms are not fully understood. This study uses integrated quantitative proteomics and phosphoproteomics analyses to characterize the differential protein profiles and phosphorylation modifications associated with HSCR. These findings reveal significant dysregulation of the extracellular matrix (ECM) remodelling pathway, suggesting its potential involvement in HSCR pathogenesis. Notably, the deubiquitinating enzyme USP46 is found to be significantly reduced in the aganglionic segments of HSCR patients. Through IP-MS, GST pull-down, and co-immunoprecipitation assays, it is demonstrated that USP46 interacts with the transcription factor POU4F1. Mechanistically, USP46 stabilizes POU4F1 via deubiquitination, increasing its binding to the heparanase (HPSE) promoter and increasing HPSE expression, which in turn promotes ECM remodelling and neural cell migration. The role of the USP46-POU4F1-HPSE signaling axis in HSCR pathogenesis is confirmed via chromatin immunoprecipitation-qPCR, luciferase reporter assays, and transwell migration assays. This study elucidates a novel regulatory mechanism linking USP46-mediated protein stabilization to ECM dynamics and neural cell migration, offering new insights into HSCR pathogenesis and potential therapeutic targets.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957917","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}
Huiping Yang, Gongyi Xiao, Dinghui Wang, Tianhua Xiong, Jing Wang, Xiaodong Jing, Bingquan Xiong, Junmei Xie, Bin Liu, Qiang She
{"title":"Inhibition of HMOX1 alleviates diabetic cardiomyopathy by targeting ferroptosis.","authors":"Huiping Yang, Gongyi Xiao, Dinghui Wang, Tianhua Xiong, Jing Wang, Xiaodong Jing, Bingquan Xiong, Junmei Xie, Bin Liu, Qiang She","doi":"10.3724/abbs.2024232","DOIUrl":"https://doi.org/10.3724/abbs.2024232","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is an important complication of chronic diabetes mellitus. However, its pathologic process and pathogenesis have not been fully elucidated. This study aims to investigate the role of ferroptosis in DCM and clarify the effect of heme oxygenase-1 (HMOX1) on DCM by targeting ferroptosis. <i>In vivo</i>, an animal model of DCM is established by subjecting mice to a high-fat diet (HFD) combined with low-dose streptozotocin (STZ) injection. We induce an <i>in vitro</i> DCM model by exposing H9C2 cells to high glucose and palmitic acid. Transcriptome sequencing reveals that the differentially expressed genes (DEGs) are enriched primarily in fatty acid metabolism and mitochondrial fatty acid β-oxidation, which are closely related to ferroptosis. The experimental results show that the diabetic microenvironment induces ferroptosis both <i>in vivo</i> and <i>in vitro</i>. Western blot analysis reveals the decreased expressions of the antioxidant proteins GPX4, SLC7A11 and ferritin in the DCM group. However, qPCR demonstrates the elevated expressions of the ferroptosis markers <i>PTGS2</i> and <i>ACSL4</i>. Biochemical indicators further support the occurrence of ferroptosis, with increased levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH), along with decreased level of glutathione (GSH). <i>In vitro</i>, intervention with high glucose and palmitic acid in H9C2 cells results in ferroptosis, which is reversed by ferrostatin-1 (Fer-1). Results show the elevated expression of HMOX1 in DCM. Moreover, knockdown of <i>HMOX1</i> ameliorates ferroptosis, thereby alleviating diabetic cardiomyopathy by reducing cardiac fibrosis and improving cardiac function. Our study elucidates the role of HMXO1 in DCM pathogenesis and provides a potential therapeutic strategy for clinical treatment.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968559","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}