Suresh C Tyagi, Irina Smolenkova, Yuting Zheng, Mahavir Singh
{"title":"Epigenetic Control of Hyperuricemia and Gout by Gene Writer DNMT1 and RNA Editor ADAR1: Mechanism of Gout and Amyloid Dissolution in Down Syndrome.","authors":"Suresh C Tyagi, Irina Smolenkova, Yuting Zheng, Mahavir Singh","doi":"10.1007/s10528-025-11038-x","DOIUrl":"https://doi.org/10.1007/s10528-025-11038-x","url":null,"abstract":"<p><p>Although DNA methyltransferase 1 (DNMT1) and RNA editor ADAR triplications exist in Down syndrome (DS), their specific roles remain unclear. DNMT methylates DNA, yielding S-adenosine homocysteine (SAH), subsequently converted to homocysteine (Hcy) and adenosine by S-adenosine homocysteine (Hcy) hydrolase (SAHH). ADAR converts adenosine to inosine and uric acid. We hypothesized that targeting epigenetic regulators and RNA editor, and inhibiting Hcy and adenosine, could alleviate DS phenotype including the congenital heart disease (CHD). DS and wild-type mice were treated with epigallocatechin gallate (EG), inhibitor of Hcy, and adenosine. Specific substrate gel zymography identified matrix metalloproteinases (MMPs)/A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) activities and MMP12/ADAMTS12 and MMP13/ADAMTS13 levels were assessed via gel zymography. Cardiac levels of DNMT1, ADAR, tissue inhibitor of metalloproteinase 1 (TIMP1), SAHH, and ten-eleven translocator (TET2), along with hydroxymethylation (a gene eraser), were measured. Calcium urate deposits in heart tissue suggested gout mechanism in DS. Robust amyloid fibers in DS mouse brain cortex were most likely dissolved by ADAMTS as its levels were elevated in tissues, with a corresponding decrease in TIMP1 in the EG group. It appears that triplication of down syndrome cell adhesion molecule (DSCAM) and cell adhesion molecule 1 (CAM1) fragment also help dissolve amyloid fibers, thus suggesting ADAMTS13/TIMP1 ratio could predict plaque dissolution. Our results indicate that cystathionine-β synthase (CBS) inhibitor as a potential therapy for amyloid dissolution.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062981","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}
Dong Liao, Wu Liu, Yunhui Jiang, Ping Zhao, Yun Yao
{"title":"TNIP1 Impacts Prognosis by Modulating the Immune Microenvironment in BRCA.","authors":"Dong Liao, Wu Liu, Yunhui Jiang, Ping Zhao, Yun Yao","doi":"10.1007/s10528-025-11034-1","DOIUrl":"https://doi.org/10.1007/s10528-025-11034-1","url":null,"abstract":"<p><p>Breast invasive carcinoma (BRCA) affects women worldwide, and despite advancements in diagnosis, prevention, and treatment, outcomes remain suboptimal. TNIP1, a novel target involved in multiple immune signaling pathways, influences tumor development and survival. However, the connection between BRCA and TNIP1 remains unclear. Analysis of data from the TCGA, GEO, Sangerbox, and Ualcan databases revealed that TNIP1 is underexpressed in BRCA tissues. This finding was corroborated by RT-PCR and immunohistochemistry. Furthermore, data from the TCGA and GEPIA2 databases, along with Sangerbox, identified TNIP1 as a marker of poor prognosis in BRCA patients. TNIP1 expression shows significant positive correlations with the BRCA Tumor Microenvironment (TME) StromalScore (R = 0.22), ImmuneScore (R = 0.25), and ESTIMATEScore (R = 0.27). Various algorithms have demonstrated a strong association between TNIP1 expression and BRCA tumor-infiltrating immune cells (TIICs). Further analysis using EPIC, TIMER, MCPCounter, QUANTISEQ, xCell, and other computational tools revealed that elevated TNIP1 expression is significantly associated with increased immune cell scores. TNIP1 expression in BRCA tumor tissues also shows a strong correlation with immune checkpoint markers. Data from the HAP database indicate that TNIP1 expression is predominantly involved in the normal skin microenvironment. Subsequent analysis using the TISCH platform with the BRCA single-cell dataset demonstrated that TNIP1 exhibits higher expression levels in immune cells compared to non-immune cells in BRCA patients. This expression is significantly positively correlated with inflammation (R = 0.25) and differentiation (R = 0.28) within the TME, while showing negative correlations with BRCA stemness (R = - 0.34) and invasion (R = - 0.22). Consequently, TNIP1 is proposed as a potential prognostic marker and therapeutic target for BRCA.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051237","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}
{"title":"Angiotensin-Converting Enzyme 2 Enhances Autophagy via the Consumption of miR-326 in a Mouse Model of Acute Lung Injury.","authors":"Xingsheng Lin, Fengying Gao","doi":"10.1007/s10528-025-11040-3","DOIUrl":"https://doi.org/10.1007/s10528-025-11040-3","url":null,"abstract":"<p><p>Angiotensin-converting enzyme 2 (ACE2) has been reported to exert a protective effect in acute lung injury (ALI), though its underlying mechanism remains incompletely understood. In this study, ACE2 expression was found to be upregulated in a mouse model of ALI induced by lipopolysaccharide (LPS) injection. ACE2 knockdown modulated the severity of ALI, the extent of autophagy, and the mTOR pathway in this model. ACE2 regulated liver kinase B1 (LKB1) gene expression by sequestering miR-326, thereby alleviating ALI severity through enhanced autophagy. In cell-based experiments, miR-326 was shown to regulate ACE2 and LKB1 expression and autophagy. Overexpression of ACE2 disrupted miR-326's regulatory effect on LKB1, suggesting that LKB1 may function as an endogenous sponge for miR-326. These findings imply that elevated ACE2 expression in lung could play enhance the autophagy via the consumption of miR-326.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045299","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}
Maryam Zamani Sani, Mohammad Mirzaei, Ali Mota, Jamal Mohammadian, Elmira Aboutalebi Vand Beilankouhi, Mohammad Rahmati
{"title":"MicroRNAs' Significance in Retinoblastoma Diagnosis and Treatment: The Little Heroes","authors":"Maryam Zamani Sani, Mohammad Mirzaei, Ali Mota, Jamal Mohammadian, Elmira Aboutalebi Vand Beilankouhi, Mohammad Rahmati","doi":"10.1007/s10528-024-10976-2","DOIUrl":"10.1007/s10528-024-10976-2","url":null,"abstract":"<div><p>One in 16, 000 live births is affected by the retinal tumor RB (retinoblastoma), which is frequently found in a child’s early years. Both of the RB1 alleles that have been locally mutated in the affected retina are present in 60 percent of cases. Retinoblastoma (RB) can be detected using a variety of techniques, including imaging of the brain and orbits, eye examinations under anesthesia (EUAs), and the discovery of cell-free tumor DNA in samples of aqueous humor or plasma. In addition to the conventional surgical, chemotherapy, and radiotherapy approaches to treating retinoblastoma, new approaches have also been developed. Oncogenes, genes of tumor suppressors, and other molecular elements involved in cell growth and division interact complexly during the pathogenesis of retinoblastoma. The development of new therapies depends on comprehending the function of these molecular components. As a small class of non-coding RNAs capable of altering gene expression, microRNAs (miRNA) are understood to represent potential targets for the treatment of cancer. This study aimed to describe the changes in microRNA expression in some types of cancer, with a particular focus on retinoblastoma.</p><h3>Graphical Abstract</h3><p>Molecular mechanism of microRNA targeting: a promising approach for retinoblastoma diagnosis and treatment. The pathogenesis of retinoblastoma involves a complex interaction between tumor suppressor genes, oncogene, and other molecular components involved in cell growth and division</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":"63 2","pages":"1176 - 1197"},"PeriodicalIF":2.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035870","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}
{"title":"Haplotypes of Chloroquine Resistance Marker Genes Among Uncomplicated Malaria Cases in Lagos, Nigeria.","authors":"Uche Thecla Igbasi, Wellington Aghoghavia Oyibo, Jun-Hu Chen, Hong Quan, Sunday Aremu Omilabu, Shen-Bo Chen, Hai-Mo Shen, Xiao-Nong Zhou","doi":"10.1007/s10528-025-11022-5","DOIUrl":"https://doi.org/10.1007/s10528-025-11022-5","url":null,"abstract":"<p><p>Drug resistance resulting from mutations in Plasmodium falciparum, that caused the failure of previously effective malaria drugs, has continued to threaten the global malaria elimination goal. This study describes the profiles of P. falciparum chloroquine resistance transporter (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr1), the genetic markers associated with 4-aminoquinoline resistance, among P. falciparum isolates from Lagos, Nigeria. Genomic DNA was extracted from the dried blood spot samples obtained from individuals with microscopically confirmed P. falciparum infection in health facilities and communities in Lagos State, Nigeria. The DNA was amplified using nested polymerase chain reaction, and sequence analysis was performed to identify single nucleotide polymorphisms in the pfcrt and pfmdr1 genes. The study showed that 82.4% (178) of the isolates had pfmdr1 wild-type, while mutations were observed at codons N86Y (11.6%) and D1246Y (3.2%). Other mutations seen were at codons Y23S (0.5%), E130K (2.3%), and S149P (0.5%). 30.8% (64) of the isolates had pfcrt wild-type (CVMNK), while 62.0% (129) had CVIET (mutant) haplotype. Other pfcrt haplotypes detected include; CVIDT (1.9%); CVMDT (1.4%); CVIKT (1.0%); CVINT (0.5%); CVMET (0.5%); CVMKT (0.5%); CVMNT (1.0%); and CVMEK (0.5%). The findings underscore the presence of uncommon pfcrt haplotypes and a high prevalence of drug-resistant pfcrt haplotypes (CVIET), alongside a high prevalence of wild-type pfmdr in Lagos. This study highlights the need for ongoing surveillance of these genetic markers to provide data that can inform decisions on malaria case management and preserve the efficacy of artemisinin combination therapies (ACTs) in Nigeria.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998118","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}
Rashid Mir, Faisal H Altemani, Naseh A Algehainy, Mohammad A Alanazi, Imadeldin Elfaki, Badr A Alsayed, Mohammad Muzaffar Mir, Syed Khalid Mustafa, Mamdoh S Moawadh, Faris J Tayeb, Jaber Alfaifi, Sael M Alatawi, Mohammed Saad Alhiwety, Mohammad Fahad Ullah
{"title":"Correction: Identification of Novel Genomic Variants in COVID-19 Patients Using Whole-Exome Sequencing: Exploring the Plausible Targets of Functional Genomics.","authors":"Rashid Mir, Faisal H Altemani, Naseh A Algehainy, Mohammad A Alanazi, Imadeldin Elfaki, Badr A Alsayed, Mohammad Muzaffar Mir, Syed Khalid Mustafa, Mamdoh S Moawadh, Faris J Tayeb, Jaber Alfaifi, Sael M Alatawi, Mohammed Saad Alhiwety, Mohammad Fahad Ullah","doi":"10.1007/s10528-025-11024-3","DOIUrl":"https://doi.org/10.1007/s10528-025-11024-3","url":null,"abstract":"","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998115","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}
{"title":"The Circadian Rhythm Regulates the Hepato-ovarian Axis Linking Polycystic Ovary Syndrome and Non-alcoholic Fatty Liver Disease.","authors":"Yibing Lan, Bihui Jin, Yuhang Fan, Yizhou Huang, Jianhong Zhou","doi":"10.1007/s10528-024-11010-1","DOIUrl":"https://doi.org/10.1007/s10528-024-11010-1","url":null,"abstract":"<p><p>This study aimed to identify shared gene expression related to circadian rhythm disruption in polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD) to discover common diagnostic biomarkers. Visceral fat RNA samples were collected from 12 PCOS and 14 non-PCOS patients, a sample size representing the clinical situation and sufficient to capture PCOS gene expression profiles. Along with liver transcriptome profiles from NAFLD patients, these data were analyzed to identify crosstalk circadian rhythm-related genes (CRRGs) between the diseases. Single-sample and single-gene gene set enrichment analyses explored immune infiltration and pathways associated with CRRGs. Diagnostic biomarkers were identified using a random forest algorithm and validated through nomograms and a mouse model. Seven crosstalk CRRGs (FOS, ACHE, FOSB, EGR1, NR4A1, DUSP1, and EGR3) were associated with clinical features, immunoinflammatory microenvironment, and metabolic pathways in both diseases. EGR1, DUSP1, and NR4A1 were identified as diagnostic biomarkers, exhibiting robust diagnostic capacity (AUC = 0.7679 for PCOS, AUG = 0.9981 for NAFLD). Nomogram validation showed excellent calibration, and independent datasets confirmed their discriminatory ability (AUC = 0.6528 for PCOS, AUC = 0.8275 for NAFLD). Additionally, ceRNA networks and androgen receptor binding sites were identified, suggesting their regulatory roles. Mouse model validation confirmed significant downregulation of EGR1, DUSP1, and NR4A1 in liver tissues, consistent with sequencing data. This study identifies crosstalk CRRGs and diagnostic biomarkers shared between PCOS and NAFLD, highlighting their roles in immune and metabolic dysregulation. These biomarkers offer the potential for improving diagnosis and guiding targeted treatments for both diseases.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998143","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}
Haihui Zhuang, Fenglin Li, Renzhi Pei, Xia Jiang, Dong Chen, Shuangyue Li, Peipei Ye, Jiaojiao Yuan, Jiangyin Lian, Jie Jin, Ying Lu
{"title":"High Expression of GPR183 Predicts Poor Survival in Cytogenetically Normal Acute Myeloid Leukemia.","authors":"Haihui Zhuang, Fenglin Li, Renzhi Pei, Xia Jiang, Dong Chen, Shuangyue Li, Peipei Ye, Jiaojiao Yuan, Jiangyin Lian, Jie Jin, Ying Lu","doi":"10.1007/s10528-025-11026-1","DOIUrl":"https://doi.org/10.1007/s10528-025-11026-1","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) with a normal karyotype (CN-AML) constitutes approximately 50% of all AML cases, presenting significant prognostic variability, and highlighting the urgent need for the identification of novel molecular biomarkers. In this study, we systematically assessed GPR183 expression levels using qRT-PCR in our clinical follow-up study which included 283 CN-AML patients. Using Kaplan-Meier analysis, we found that patients with high GPR183 expression levels exhibited significantly worse overall survival (OS) (P = 0.046) and event-free survival (EFS) (P = 0.030) compared to those with low GPR183 expression. Comprehensive univariate and multivariate Cox regression analyses confirmed that GPR183 expression is a prognostic factor for OS and EFS (P < 0.05). To further validate these findings, we analyzed an independent cohort of 104 CN-AML patients from the GSE71014 dataset, corroborating our primary results, and indicating that high GPR183 expression is associated with poorer survival outcomes. Additionally, RNA-seq data from the GSE71014 dataset were analyzed by Gene Set Enrichment Analysis (GSEA). The results suggested that GPR183 may influence disease progression through the activation of the \"TNFa Signaling Via NF-κB\" pathway. Collectively, these findings suggested that GPR183 could serve as a valuable prognostic biomarker in CN-AML, offering insights into the underlying mechanisms of disease progression.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998132","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}
{"title":"METTL14 Promotes the Osteogenic Differentiation of Human Bone Marrow Stromal Cells via m6A-Dependent Stabilization of USP7 mRNA.","authors":"Yu Leng, Zhiwen Liu, Jun Min, Qing Ke, Yiqing Shao, Junyan Lai, Jing Zhao","doi":"10.1007/s10528-024-10999-9","DOIUrl":"https://doi.org/10.1007/s10528-024-10999-9","url":null,"abstract":"<p><p>Osteoporosis (OP) is a common clinical bone disease that can cause a high incidence of non-stress fractures and is one of the main degenerative diseases that endangers the health and life of middle-aged and older women. The mechanism underlying the abnormal differentiation and function of human bone marrow stem cells (hBMSCs) remains to be elucidated. Cell proliferation and differentiation were determined using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, alkaline phosphatase (ALP) staining, and Alizarin Red Staining. The interaction between insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and ubiquitin-specific protease 7 (USP7) was predicted and validated using bioinformatics approaches, luciferase assays, RNA immunoprecipitation (RIP), and immunoprecipitation (IP). Actinomycin D treatment was used to test the stability of mRNA in the various groups. Methyltransferase-like 14 (METTL14) expression was increased in osteogenic differentiation medium-induced hBSMCs and was associated with enhanced osteogenic differentiation. METTL14 regulated the expression USP7 by modulating its N<sup>6</sup>-methyladenosine (m6A) level. IGF2BP2 exerted an m6A-dependent effect on USP7 mRNA stability and USP7 increased sirtuin 1 (SIRT1) expression in hBMSCs by enhancing SIRT1 deubiquitination. METTL14 stimulated the osteogenic differentiation of hBMSCs through the m6A-IGF2BP2-USP7 pathway and promoted hBMSCs osteogenic development via SIRT1-Bmi1 signaling. METTL14 stimulated the osteogenic differentiation of hBMSCs by stabilizing USP7 mRNA in an m6A-dependent manner. USP7 was also stabilized by IGF2BP2 and it regulated downstream SIRT1-Bmi1 signaling.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998135","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}