1.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
2.Predictive value of serum Perilipin 5 and growth hormone releasing peptide levels in the occurrence of major adverse cardiovascular events in patients with acute myocardial infarction
International Journal of Laboratory Medicine 2025;46(3):287-291,296
Objective To explore the predictive value of serum Perilipin 5 and growth hormone-releasing peptide(Ghrelin)levels in the occurrence of major adverse cardiovascular events(MACE)in patients with a-cute myocardial infarction(AMI).Methods A total of 148 patients with AMI treated in the First Affiliated Hospital of Xi'an Jiaotong University from February 2020 to July 2023 were selected as AMI group.Accord-ing to the occurrence of MACE,the patients were divided into the occurrence group(46 cases)and the non-oc-currence group(102 cases).Another 148 healthy subjects who underwent physical examination in the same period were selected as the control group.Serum Perilipin 5 and Ghrelin levels were detected by enzyme-linked immunosorbent assay.Multivariate Logistic regression analysis was conducted to analyze the influencing fac-tors of MACE occurrence in AMI patients,and the predictive value of serum Perilipin 5 and Ghrelin on MACE occurrence in AMI patients was analyzed by drawing receiver operating characteristic(ROC)curve.Results The serum levels of Perilipin 5 and Ghrelin in AMI group were significantly lower than those in con-trol group,and the difference was statistically significant(P<0.05).The proportion of cardiac function gradeⅢ to Ⅳ,the level of hypersensitive C-reactive protein and the proportion of coronary artery involved in the disease in the occurrence group were significantly higher than those in the non-occurrence group,while the se-rum levels of Perilipin 5,Ghrelin and left ventricular ejection fraction were significantly lower than those in the non-occurrence group,and the difference was statistically significant(P<0.05).Multivariate Logistic re-gression analysis showed that grade Ⅲ to Ⅳ and coronary artery involvement were the risk factors for MACE in AMI patients(P<0.05),and Perilipin 5 and Ghrelin were the protective factors for MACE in AMI patients(P<0.05).ROC curve analysis results showed that the area under the curve predicted by serum Perilipin 5 and Ghrelin combined was 0.915,which was better than that predicted by serum Perilipin 5 and Ghrelin a-lone.Conclusion Serum Perilipin 5 and Ghrelin levels have high predictive value for MACE occurrence in AMI patients.
3.Diagnostic value of serum PDCD5 and ADAMTS13 for myocardial injury after percutaneous coronary intervention in patients with coronary heart disease
International Journal of Laboratory Medicine 2025;46(12):1508-1513
Objective To investigate the diagnostic value of serum programmed cell death 5(PDCD5)com-bined with a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13(ADAMTS13)for myocardial injury after percutaneous coronary intervention(PCI)in patients with coronary heart disease.Methods Totally 150 patients with coronary heart disease in the First Affiliated Hospital of Xi'an Jiaotong University from January 2021 to October 2023 were selected and divided into uninjured group(108 cases)and injured group(42 cases)based on whether myocardial injury occurred after PCI.Fully automated biochemical analyzer was applied to detect levels of creatine kinase(CK),creatine kinase isoenzyme(CK-MB),cardiac tro-ponin I(cTnI),enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of PDCD5 and ADAMTS13,and Doppler ultrasound detector was applied to detect left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD),and left ventricular ejection fraction(LVEF).In addition,SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery(SYNTAX)score was used to evaluate the severity of coronary artery disease.Multivariate Logistic regression was applied to analyze the influencing factors of myocardial injury after PCI.Pearson correlation was used to analyze the correlation between PDCD5,ADAMTS13 levels with myocardial enzyme and cardiac function indicators.Re-ceiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of PDCD5 and AD-AMTS13 in patients with myocardial injury after PCI.Results Compared with the non injury group,the inju-ry group had higher levels of cTnI、CK-MB、LVEDD、LVESD、SYNTAX score and PDCD5(P<0.05),and lower LVEF、ADAMTS13(P<0.05).Multivariate Logistic regression analysis showed that elevated cTnI(OR=1.862)and PDCD5(OR=1.615)were independent risk factors for myocardial injury(P<O.05),while elevated LVEF(OR=0.652)and ADAMTS13(OR=0.426)were independent protective factors for myocardial injury(P<0.05).Correlation analysis shows that level of PDCD5 was positively correlated with cTnI,CK,CK-MB,LVEDD,LVESD and SYNTAX score,and negatively correlated with LVEF,while level of ADAMTS13 was negatively correlated with cTnI,CK,CK-MB,LVEDD,LVESD and SYNTAX score,and positively correlated with LVEF(P<0.05).ROC curve analysis showed the area under the curve(AUC)for diagnosing myocardial injury with PDCD5 and ADAMTS13 was larger than single diagnosis(P<0.05).Con-clusion Patients with myocardial injury have elevated level of PDCD5 and decreased level of ADAMTS13,which are correlated with myocardial enzyme and cardiac function indicators.The combined diagnosis of myo-cardial injury in patients with coronary heart disease after PCI has certain value.
4.Correlation between serum FABP4,ANGPTL4,CA125 and the cardiac function classification and recurrence after radiofrequency ablation in patients with paroxysmal atrial fibrillation
International Journal of Laboratory Medicine 2025;46(13):1636-1640
Objective To explore the correlation between serum fatty acid binding protein 4(FABP4),an-giopoietin like protein 4(ANGPTL4),carbohydrate antigen 125(CA125)and the cardiac function classifica-tion and recurrence after radiofrequency ablation in patients with paroxysmal atrial fibrillation(PAF).Meth-ods Totally 126 patients with PAF who underwent radiofrequency ablation in the First Affiliated Hospital of Xi'an Jiaotong University from March 2022 to March 2023 were selected as the PAF group.They were divided into the mild group and the severe group according to the cardiac function classification,and were further di-vided into the recurrence group and the non-recurrence group based on the postoperative follow-up results.Another 116 healthy individuals who underwent physical examinations in this hospital during the same period were selected as the control group.The levels of serum FABP4,ANGPTL4 and CA125 were detected by en-zyme-linked immunosorbent assay(ELISA),the correlations among the levels of serum FABP4,ANGPTL4 and CA125 in patients with PAF were analyzed by Pearson method,and the influencing factors of postopera-tive recurrence in patients with PAF were analyzed by multivariate Logistic regression.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum FABP4,ANGPTL4,and CA125 levels for postoperative recurrence in patients with PAF.Results Compared with the control group,the levels of serum FABP4 and CA125 in the PAF group were increased(P<0.05),and the level of ANGPTL4 was de-creased(P<0.05).Compared with the mild group,the levels of serum FABP4 and CA125 in the severe group increased(P<0.05),and the level of ANGPTL4 decreased(P<0.05).The levels of serum ANGPTL4 were negatively correlated with those of FABP4 and CA125(r=-0.467,—0.513,both P<0.001),and the level of serum FABP4 was positively correlated with that of CA125(r=0.436,P<0.001).The levels of serum FABP4 and CA125 in the recurrence group were increased compared with those in the non-recurrence group(P<0.05),and the level of ANGPTL4 was decreased(P<0.05).Hypertension,the use of antiarrhythmic drugs,serum FABP4,CA125,and ANGPTL4 were the influencing factors for postoperative recurrence in pa-tients with PAF(P<0.05).The combined prediction value of serum FABP4,ANGPTL4 and CA125 for re-currence after radiofrequency ablation in patients with PAF was superior to that of each index alone(P<0.05).Conclusion The serum levels of FABP4 and CA125 in PAF patients increase,while the level of AN-GPTL4 decreases.All three indicators are closely related to cardiac function grading and recurrence after ra-diofrequency ablation.
5.Localization and identification of the mutant gene in the loop-tail mouse
Fenli ZHANG ; Bing CHEN ; Zhengfeng XUE ; Yi LI
Chinese Journal of Comparative Medicine 2014;(12):20-23,26
Objective To define the loci of the mutant gene in the loop-tail mouse.Methods To study the heredity pattern, loop-tail mice were mated with normal C57BL/6J and C3H mice.Their offsprings with loop-tail or normal phenotype were registered respectively.Microsatellite marker D1Mit113 and D1Mit149 were used to locate the mutant gene.Based on fine mapping, the candidate gene Vangl2 was found.Vangl2 gene from the loop-tail mice was amplified by PCR followed by sequencing.Incision enzyme FspBI ( BfaI ) identified the genotype of offspring from loop-tail mice intercrossing.Results Heredity test indicated that the loop-tail phenotype was controlled by a single dominant gene not with 100%penetrance but was affected by genetic background.A C-to-T transversion was at the 1345bp in Vangl2 gene of the loop-tail mice.Conclusions The C-to-T transversion introduces a pre-termination codon of amino acids and causes the phenotype of loop-tail phenotype.None homozygous mice were found in the offsprings, suggesting that the homozygous mice are lethal.

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