Biochemical Genetics最新文献

LncRNA GAS5 Restrains Hepatocellular Carcinoma by Targeting the miR-18a-5p-CADM2 Axis. LncRNA GAS5靶向miR-18a-5p-CADM2轴抑制肝细胞癌

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-16 DOI: 10.1007/s10528-026-11451-w

Shaoying Ke, Congren Wang, Shaoze Lin, Lingju Hong, Gongle Wu

{"title":"LncRNA GAS5 Restrains Hepatocellular Carcinoma by Targeting the miR-18a-5p-CADM2 Axis.","authors":"Shaoying Ke, Congren Wang, Shaoze Lin, Lingju Hong, Gongle Wu","doi":"10.1007/s10528-026-11451-w","DOIUrl":"https://doi.org/10.1007/s10528-026-11451-w","url":null,"abstract":"Long non-coding RNAs (lncRNAs) are key regulators in hepatocellular carcinoma (HCC) progression, yet the function of lncRNA GAS5 in HCC remains controversial. GAS5 expression was analyzed across multiple public datasets. Overexpression experiments were performed in HCC cells to evaluate GAS5's biological role. Bioinformatic prediction, luciferase reporter experiments, and rescue assays were used to elucidate the molecular mechanism. Xenograft mice were established to confirm GAS5's in vivo effects. GAS5 levels were markedly reduced in HCC tissues. Excessive GAS5 suppressed cell viability and colony formation, induced G0/G1 arrest, promoted apoptosis, and inhibited migration and invasion. Mechanistically, GAS5 functioned as a competing endogenous RNA to inhibit miR-18a-5p and restore the expression of the tumor suppressor CADM2. The direct interactions between GAS5 and miR-18a-5p, and between miR-18a-5p and the CADM2 3'-UTR, were validated by luciferase assays. Rescue assays demonstrated that miR-18a-5p overexpression or CADM2 silencing reversed the tumor-suppressive effects of GAS5. In the xenograft mice, excessive GAS5 significantly impaired tumorigenesis and modulated apoptosis- and EMT-related markers. GAS5 suppresses HCC by modulating the miR-18a-5p-CADM2 axis. Our findings offer a new perspective into HCC tumorigenesis and suggest that GAS5 and its downstream network may serve as potential therapeutic targets.","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Hedyotis diffusa Willd-Scutellaria barbata D.Don Suppresses Colorectal Cancer Liver Metastasis by Targeting hsa_circ_0039933-Mediated Epithelial-Mesenchymal Transition. 白花蛇舌草-五花芩抑制大肠癌肝转移的作用机制

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-01 Epub Date: 2026-06-08 DOI: 10.1007/s10528-026-11392-4

Shanmin Yuan, Sha Li, Cong Chen

{"title":"Hedyotis diffusa Willd-Scutellaria barbata D.Don Suppresses Colorectal Cancer Liver Metastasis by Targeting hsa_circ_0039933-Mediated Epithelial-Mesenchymal Transition.","authors":"Shanmin Yuan, Sha Li, Cong Chen","doi":"10.1007/s10528-026-11392-4","DOIUrl":"10.1007/s10528-026-11392-4","url":null,"abstract":"Colorectal cancer (CRC) liver metastasis remains a major cause of mortality, necessitating novel therapeutic strategies. Hedyotis diffusa Willd -Scutellaria barbata D.Don (HD-SB), a traditional Chinese herbal formulation, has demonstrated anti-tumor potential. However, its mechanism in CRC metastasis, particularly through the regulation of circular RNAs, remains unexplored. A CRC liver metastasis model was established in Balb/c nude mice via intrasplenic injection of HCT-15 cells. Mice received HD-SB treatment. Hematoxylin-eosin staining, Masson staining, and immunohistochemistry (Ki67 and Cytokeratin 19 [CK19]) were carried out to observe pathologic changes in CRC liver metastases. In vitro, HCT-15 cells were treated with tumor necrosis factor-α (TNF-α) to induce metastasis. hsa_circ_0039933 was knocked down and overexpressed in vitro. Transwell, wound healing, EdU, and cell counting kit-8 assays were employed to assess cell invasion, migration and proliferation, respectively. The levels of epithelial-mesenchymal transition (EMT) markers were evaluated by quantitative real-time polymerase chain reaction and western blot. HD-SB treatment dose-dependently reduced hepatic tumor nodules, fibrosis, Ki67 and CK19 expression in vivo, with high-dose HD-SB showing superior efficacy. EMT reverse (upregulated E-cadherin, downregulated N-cadherin/Vimentin) and hsa_circ_0039933 suppression were observed in HD-SB treated CRC mouse. In vitro, HD-SB attenuated TNF-α-induced proliferation, migration, and invasion, synergizing with hsa_circ_0039933 knockdown to suppress EMT and metastatic phenotypes. Conversely, hsa_circ_0039933 overexpression exacerbated TNF-α-driven aggressiveness, which was effectively counteracted by HD-SB. Collectively, HD-SB inhibits CRC liver metastasis by targeting hsa_circ_0039933 and modulating EMT. These findings highlight HD-SB as a promising circRNA-directed therapeutic agent for metastatic CRC.","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"7608-7627"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

ANGPTL1 Inhibits the Growth, Migration, and Angiogenesis of Gastric Cancer Cells by Downregulating VEGFA Expression. ANGPTL1通过下调VEGFA表达抑制胃癌细胞生长、迁移和血管生成

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-01 Epub Date: 2026-06-01 DOI: 10.1007/s10528-026-11406-1

Lingli Jin, Guangxin Lu, Rui Shang, Junhua Hu, Chaobei Zhu, Tingting Yan

{"title":"ANGPTL1 Inhibits the Growth, Migration, and Angiogenesis of Gastric Cancer Cells by Downregulating VEGFA Expression.","authors":"Lingli Jin, Guangxin Lu, Rui Shang, Junhua Hu, Chaobei Zhu, Tingting Yan","doi":"10.1007/s10528-026-11406-1","DOIUrl":"10.1007/s10528-026-11406-1","url":null,"abstract":"Gastric cancer (GC) remains one of the most common malignant tumors worldwide, with high incidence and mortality rates. Angiopoietin-like protein 1 (ANGPTL1), a member of the ANGPTL family, is known to function as an anti-angiogenic factor and tumor suppressor. However, its role and underlying mechanisms in GC development have not been investigated and require further investigation. Protein expression levels were analyzed using western blotting and immunofluorescence (IF) assays. Cell viability was assessed using the CCK-8 assay, and cell proliferation was evaluated through colony formation assays. Cell migration and invasion were examined using Transwell assays. Angiogenic capacity was determined through tube formation assays. The VEGFA mRNA expression was detected through RT-qPCR. The level of VEGFA was confirmed through ELISA. The tumor size, volume and weight were confirmed through the in vivo assay. The CD31 protein expression was verified though IHC assay. ANGPTL1 was found to be expressed at lower levels in GC cells, and negatively correlated with VEGFA. ANGPTL1 significantly inhibited GC cell proliferation, migration, and invasion. Furthermore, ANGPTL1 suppressed angiogenesis in vitro. Mechanistically, it was observed that ANGPTL1 overexpression reduced VEGFA expression, and ANGPTL1 can interact with VEGFA. Importantly, reintroduction of VEGFA reversed the inhibitory effects of ANGPTL1 on GC progression. Lastly, VEGFA overexpression retarded the tumor growth in vivo. This study demonstrates that ANGPTL1 inhibits the growth, migration, and angiogenesis of GC cells by downregulating VEGFA expression. These findings suggest that ANGPTL1 may serve as a promising therapeutic target for gastric cancer treatment.","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"7465-7481"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

FTO Deficiency Inhibits Vascular Endothelial Cell Apoptosis and Improved Mitophagy in Obesity-Related Hypertension by Enhancing NDRG1 m6A Methylation. FTO缺乏通过增强NDRG1 m6A甲基化抑制肥胖相关性高血压的血管内皮细胞凋亡和线粒体自噬

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-01 Epub Date: 2026-06-04 DOI: 10.1007/s10528-026-11410-5

Qinglei Gan, Na Yang

{"title":"FTO Deficiency Inhibits Vascular Endothelial Cell Apoptosis and Improved Mitophagy in Obesity-Related Hypertension by Enhancing NDRG1 m6A Methylation.","authors":"Qinglei Gan, Na Yang","doi":"10.1007/s10528-026-11410-5","DOIUrl":"10.1007/s10528-026-11410-5","url":null,"abstract":"Vascular endothelial dysfunction contributes to obesity-related hypertension, yet its mechanisms remain unclear. This study examined the role of N6-methyladenosine (m6A) in this process using in vivo and in vitro models. C57BL/6J mice fed a high-fat diet (HFD) developed obesity-related hypertension, while oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs) simulated endothelial injury. Global m6A levels were assessed via dot blot, and m6A regulators were quantified by qPCR. Endothelial function was evaluated through viability (CCK-8), apoptosis (flow cytometry), and mitophagy (Western blot and immunofluorescence staining). Mechanistic studies included methylated RNA immunoprecipitation (MeRIP) and dual-luciferase assays. Results showed HFD reduced m6A levels but elevated Fto expression in mice, while ox-LDL decreased m6A levels and upregulated FTO in HAECs. FTO knockdown in HAECs enhanced viability and mitophagy while suppressing apoptosis under ox-LDL stress. Mechanistically, FTO silencing increased m6A methylation on NDRG1 mRNA, leading to its degradation via YTHDF2 recognition. NDRG1 overexpression reversed these effects, restoring apoptosis while reducing mitophagy and viability. These findings reveal that FTO depletion attenuates endothelial dysfunction in obesity-related hypertension by enhancing m6A-mediated suppression of NDRG1, highlighting the FTO/m6A/NDRG1/YTHDF2 axis as a therapeutic target for vascular protection.","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"7523-7541"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Identification of Key Genes Related to SUMOylation and Potassium Channels and Their Mechanism of Influence on Pulmonary Arterial Hypertension. SUMOylation和钾通道相关关键基因的鉴定及其对肺动脉高压的影响机制。

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-01 Epub Date: 2026-04-30 DOI: 10.1007/s10528-026-11388-0

Lingyun Gao, Wei Huang, Qianqian Wang, Sen Lei

引用次数: 0

Bacillus spp. Mediated Growth Enhancement and Antioxidative Defence Activation in Peppermint (Mentha piperita L.). 芽孢杆菌介导的薄荷生长促进和抗氧化防御激活。

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-01 Epub Date: 2026-05-28 DOI: 10.1007/s10528-026-11396-0

Vagmi Singh, Shivani Chandra, Ram Kishor, Nidhi Maurya, Suaib Luqman, Rajesh Kumar Verma, Anju Kumari Yadav, Birendra Kumar

{"title":"Bacillus spp. Mediated Growth Enhancement and Antioxidative Defence Activation in Peppermint (Mentha piperita L.).","authors":"Vagmi Singh, Shivani Chandra, Ram Kishor, Nidhi Maurya, Suaib Luqman, Rajesh Kumar Verma, Anju Kumari Yadav, Birendra Kumar","doi":"10.1007/s10528-026-11396-0","DOIUrl":"10.1007/s10528-026-11396-0","url":null,"abstract":"Peppermint (Mentha piperita L.) is a valuable medicinal and aromatic herb cultivated globally for its essential oil, prized for its therapeutic and flavouring properties. The productivity and essential oil quality of peppermint is strongly influenced by the intervention of biotic and abiotic elicitors, which eventually induces plant growth dynamics, redox homeostasis, and secondary metabolite biosynthesis. This study evaluates the effect of five plant growth promoting rhizobacteria (PGPRs): Bacillus tequilensis (T1), Bacillus subtilis (T2), Bacterium strain (T3), Bacillus thuringiensis (T4), and Bacillus cereus (T5), to access the modulation efficiency of these plant probionts over morphological, physiological, and biochemical parameters of peppermint variety CIM-Suras. The surface sterilized, uniform sized suckers of a menthol-rich peppermint variety CIM-Suras were inoculated with five aforementioned Bacillus spp., endowed with phosphate solubilization, ammonia production, siderophore production, and Indole Acetic Acid production efficiencies, in triplicate. The results of the study revealed that T2 (Bacillus subtilis) has significantly enhanced the photosynthetic process, contents of chlorophyll (64.71%), accumulation of proline (43.17%), SOD (24.89%), and catalase (56.33%), over the control, followed by T1 (Bacillus tequilensis), and T4 (Bacillus thuringiensis). Treatment with Bacillus subtilis (T2) showing maximum improvement in studied morphological, physiological and biochemical parameters in peppermint suggests the potential of the isolate to abate the oxidative damage of the cells during altering environmental conditions. These findings underscore the efficiency of peppermint-native Bacillus-based PGPRs, especially B. subtilis, for improving crop growth, stress resilience, and essential oil yield in a menthol-rich cultivar. This approach offers a sustainable alternative to synthetic fertilizers to improve peppermint productivity.","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"7387-7409"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

COVID-19 as a Modifier of Genetically Determined Coagulation Phenotype: Implications for Precision Risk Stratification After Infection. COVID-19作为基因决定凝血表型的修饰因子：感染后精确风险分层的意义

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-01 Epub Date: 2026-06-09 DOI: 10.1007/s10528-026-11414-1

Oleg Alexandrovich Perevezentsev, Ilgar Salekh Mamedov, Dmitry Vladimirovich Burtsev

{"title":"COVID-19 as a Modifier of Genetically Determined Coagulation Phenotype: Implications for Precision Risk Stratification After Infection.","authors":"Oleg Alexandrovich Perevezentsev, Ilgar Salekh Mamedov, Dmitry Vladimirovich Burtsev","doi":"10.1007/s10528-026-11414-1","DOIUrl":"10.1007/s10528-026-11414-1","url":null,"abstract":"Persistent endothelial dysfunction and coagulation abnormalities are increasingly recognized as central components of post-COVID syndrome. However, substantial interindividual variability in long-term coagulation biomarkers suggests the presence of genetically determined susceptibility factors capable of modulating post-infectious thromboinflammatory responses. To determine whether common prothrombotic genetic variants modify long-term D-dimer and INR levels after COVID-19 and to assess their value for precision risk stratification. A controlled observational cohort study included 504 adults aged 18-50 years examined more than two years after PCR-confirmed COVID-19 and 270 control individuals without clinically significant SARS-CoV-2 infection. Genotyping of F2 c.20210G > A, F5 c.1691G > A (Factor V Leiden), and MTHFR c.C677T was performed using real-time PCR. D-dimer and international normalized ratio (INR) were measured monthly for 12 months and averaged. Log-transformed D-dimer was analyzed using multivariable linear regression with interaction terms. All three variants were independent predictors of D-dimer. In adjusted models, F2 GA (+ 31%), F5 GA (+ 37%), MTHFR CT (+ 34%), and MTHFR TT (+ 67%) were associated with higher D-dimer levels (all p < 0.001). Significant amplification of genetic effects was observed in post-COVID individuals (Group × Genotype interaction p < 0.01). INR showed no genotype association. COVID-19 acts as a long-term modifier of inherited thrombophilia phenotypes. Incorporating genetic profiling into post-COVID evaluation may enable precision identification of individuals at risk for persistent hypercoagulability.","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"7665-7677"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Circular RNA hsa_circ_0002473 Boosts Gastric Cancer Progression via the miR-873-5p/TEAD1 Axis. 环状RNA hsa_circ_0002473通过miR-873-5p/TEAD1轴促进胃癌进展

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-01 Epub Date: 2026-06-04 DOI: 10.1007/s10528-026-11407-0

Min Wang, Zhouying Wu, Ruiying Tong, Yikun Geng, Feng Li, Xue Huo, Lan Yu

{"title":"Circular RNA hsa_circ_0002473 Boosts Gastric Cancer Progression via the miR-873-5p/TEAD1 Axis.","authors":"Min Wang, Zhouying Wu, Ruiying Tong, Yikun Geng, Feng Li, Xue Huo, Lan Yu","doi":"10.1007/s10528-026-11407-0","DOIUrl":"10.1007/s10528-026-11407-0","url":null,"abstract":"Circular RNAs (circRNAs) display cancer-specific expression profiles associated with the prevalence and fatality rates of gastric cancer (GC). Although the functions of certain circRNAs in GC advancement have been clarified, a recently identified circRNA hsa_circ_0002473, require further examination. The current study reveals that hsa_circ_0002473 facilitates gastric cancer progression. Initially, we observed that hsa_circ_0002473 exhibited high expression levels in gastric cancer tissue and cells. Subsequent investigations utilizing the Incucyte S3 imaging system, colony formation assay, scratch wound healing assay, and mouse xenograft models demonstrated that knockdown of hsa_circ_0002473 significantly inhibited the proliferation and migration of GC cells. Additionally, dual-luciferase assays confirmed hsa_circ_0002473 directly binds miR-873-5p and miR-873-5p targeting of the TEAD1 3'UTR. Crucially, rescue experiments demonstrated that miR-873-5p restoration or TEAD1 knockdown reduced hsa_circ_0002473-driven GC cells proliferation and migration. Our findings demonstrate that hsa_circ_0002473 elevates TEAD1 expression by competitively sequestering miR-873-5p, thereby promoting gastric cancer progression. This newly identified circRNA regulatory axis could enrich the genetic characteristics of GC, provide a possible medicinal genetic target for GC, and present a new perspective for GC molecular diagnosis.","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"7501-7522"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Association Between Ticagrelor and Glucose Homeostasis Regulation: Insights from Genetic and Transcriptomic Analyses. 替格瑞洛与葡萄糖稳态调节之间的关系：来自遗传和转录组学分析的见解。

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-01 Epub Date: 2026-05-20 DOI: 10.1007/s10528-026-11398-y

Zhipeng Xie, Heshuo Ma, Yingjian Liu, Weihua Lai

{"title":"Association Between Ticagrelor and Glucose Homeostasis Regulation: Insights from Genetic and Transcriptomic Analyses.","authors":"Zhipeng Xie, Heshuo Ma, Yingjian Liu, Weihua Lai","doi":"10.1007/s10528-026-11398-y","DOIUrl":"10.1007/s10528-026-11398-y","url":null,"abstract":"Emerging evidence has demonstrated the additional therapeutic benefits of ticagrelor in acute coronary syndrome (ACS) patients with diabetes. However, the underlying mechanisms of this association remain elusive. Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on ticagrelor, plasma proteomics and type 2 diabetes was employed to identify causal mediator proteins. RNA sequencing (RNA-seq) of ticagrelor-treated HepG2 cells revealed the molecular pathways regulating glucose metabolism. Genetically proxied ticagrelor was significantly associated with a reduced risk of diabetes (OR = 0.859, 95% CI: 0.783-0.934, P = 7.98E-05), and 24.41% of this effect was mediated by upregulation of BDH2 protein. In vitro experiments confirmed the enhanced effect of ticagrelor on glucose consumption. Transcriptome analysis revealed that mitochondrial respiratory chain transfer and oxidative phosphorylation (OXPHOS) were significantly enriched, and genes related to ATP biosynthesis were significantly upregulated. These findings highlight the non-platelet function of ticagrelor in maintaining glucose homeostasis, providing insights into potential drug repurposing in the future.","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"7356-7372"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

2,6-Diaminopurine Induces ACTN3 Premature Termination Codon Readthrough. 2,6-二氨基嘌呤诱导ACTN3过早终止密码子读取

IF 1.9 4区生物学

Biochemical Genetics Pub Date : 2026-10-01 Epub Date: 2026-04-03 DOI: 10.1007/s10528-026-11371-9

Nagakatsu Harada

{"title":"2,6-Diaminopurine Induces ACTN3 Premature Termination Codon Readthrough.","authors":"Nagakatsu Harada","doi":"10.1007/s10528-026-11371-9","DOIUrl":"10.1007/s10528-026-11371-9","url":null,"abstract":"The ACTN3 gene encodes a sarcomeric α-actinin-3 protein, which forms an anti-parallel dimer and constitutes the Z-lines in human skeletal muscle fast-twitch fibers. In human ACTN3, a nonsense mutation that replaces a CGA codon for the 577th arginine (R) residue with a TGA premature termination codon (PTC; specified as X) produces the R577X polymorphism. Since ACTN3 577X mRNA is targeted and degraded by a cellular nonsense-mediated mRNA decay (NMD) system, individuals with the homozygous ACTN3 577XX genotype do not express α-actinin-3 protein in the muscles, resulting in a decrease in speed-oriented athletic performance and muscle mass. The PTC has been a target for translational readthrough using aminoglycoside antibiotics, which enable the full-length α-actinin-3 protein to be produced from the ACTN3 577X gene. However, this effect requires a supraphysiological dose (mM levels) and supportive NMD inhibition. Using expression plasmids and HEK293 cultured cells, in this paper I show that 2,6-diaminopurine (DAP), a recently identified natural compound with translational readthrough activity, can produce a full-length α-actinin-3 protein from the ACTN3 577X gene even when used alone and at a relatively low concentration (µM levels). Most ACTN3 577X alleles likely contain three missense mutations (Q523R, R628C, and R776Q). Full-length α-actinin-3 proteins derived from the ACTN3 577X gene formed more homodimers than α-actinin-3 proteins derived from the ACTN3 577R gene. These results indicate that DAP-induced translational readthrough has the potential to restore function to the lost gene ACTN3 577X in humans.","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"7821-7834"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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