Biochemical Genetics最新文献

{"title":"Analysis of the Main Checkpoints of the JNK-MAPK Pathway in HTLV-1-Associated Leukemia/Lymphoma via Boolean Network Simulation.","authors":"Shayan Mardi, Arash Letafati, Amin Hosseini, Reza Faraji, Parastoo Hosseini, Sayed-Hamidreza Mozhgani","doi":"10.1007/s10528-024-10916-0","DOIUrl":"https://doi.org/10.1007/s10528-024-10916-0","url":null,"abstract":"<p><p>The c-Jun N-terminal kinase (JNK) pathway is a signal transduction pathway that plays a critical role in cell growth and survival. Its dysregulation is related to various cancers, including adult T-cell leukemia/lymphoma (ATLL), an aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection. There is currently no vaccine or definitive treatment for ATLL. This research aimed to identify the JNK-MAPK pathway checkpoints to identify possible therapeutic targets using Boolean network analysis. First, the genes involved in the JNK pathway and their interactions were identified and mapped. Next, a Boolean network analysis was performed using the R programming language, which suggested protein kinase B (AKT) and MAP kinase phosphatase (MKP) for further evaluation. Finally, to confirm the effect of these two genes, a clinical study was conducted among ATLL patients and healthy individuals. The quantitative real time polymerase chain reaction (qRT‒PCR) results revealed a statistically significant decrease in the expression of AKT and MKP in ATLL patients compared to normal controls. This highlights the potential role of these two genes as potential therapeutic targets in ATLL.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338735","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":"Exploring Genetic Diversity for High CBD Content in Cannabis Accessions in Tropical and Subtropical Regions of India.","authors":"Nashra Aftab, Akancha Gupta, Priyanka Prasad, Himanshu Kumar Kushwaha, Ram Kishor, Vagmi Singh, Shivani Chandra, K T Venkatesha, Dipender Kumar, Narendra Kumar, Karuna Shanker, Namita Gupta, Birendra Kumar","doi":"10.1007/s10528-024-10914-2","DOIUrl":"https://doi.org/10.1007/s10528-024-10914-2","url":null,"abstract":"<p><p>Cannabis, also known as marijuana or hemp, has been utilized since ancient times for industrial, religious, recreational, and medical uses. However, regardless of the intended use, there are legal requirements for quantitative testing of cannabinoids across the supply chains. This investigation aimed to evaluate the genetic diversity of 54 Cannabis samples collected from tropical and subtropical regions in India. The research found a high genotypic coefficient of variation (GCV), phenotypic coefficient of variation (PCV), heritability, and genetic advance for total cannabidiol (CBD) content. The genotypic and phenotypic correlation among the morpho-chemical characters revealed strong positive correlations among most characters. Clustering and Principal component analysis identified three accessions in cluster II (CIM-CS-65, CIM-CS-189 & CIM-CS-64) with high CBD content that could be used for breeding and as sources of high CBD content in Cannabis. CIM-CS-64, with its high CBD content with 0.01%THC content, holds potential as a valuable parental line for utilization in hybridization programs and recombinant breeding. Furthermore, in accordance with the NDPC Act of 1985, CIM-CS-64 can be commercialized for medicinal purposes, making it a promising source for the development of medicinal CBD products.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338738","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":"Study on the Mechanism of FOXA2 Activation on Glutathione Metabolic Reprogramming Mediated by ETV4 Transcription to Facilitate Colorectal Cancer Malignant Progression.","authors":"Xiangcheng Zhang, Yali He, Jiayue Shen, Bingchuan Zhou, Huabo Qin, Shuai Zhang, Zixiang Huang","doi":"10.1007/s10528-024-10918-y","DOIUrl":"https://doi.org/10.1007/s10528-024-10918-y","url":null,"abstract":"<p><p>The metabolic imbalance of glutathione (GSH) has been widely recognized in most cancers, but the specific molecular mechanism of GSH metabolic regulation in the malignant progression of colorectal cancer (CRC) is unexplored. The objective of our project is to elucidate whether ETV4 affects the malignant progression of CRC through GSH metabolic reprogramming. Bioinformatics and molecular experiments measured the expression of ETV4 in CRC, and in vitro experiments explored the impact of ETV4 on CRC malignant progression. The Kyoto Encyclopedia of Genes and Genomes (KEGG) identified the pathway of ETV4 enrichment. The bioinformatics approach identified FOXA2 as an upstream regulatory factor of ETV4. The dual-luciferase assay, chromatin immunoprecipitation (ChIP) and co-immunoprecipitation (Co-IP) experiment verified the binding relationship between ETV4 and FOXA2. Cell viability, migration, and invasion abilities were determined by conducting CCK-8, wound healing, and Transwell assays, respectively. The expression levels of N-cadherin, E-cadherin, and vimentin were determined by utilizing immunofluorescence (IF). Metabolism-related enzymes GCLM, GCLC, and GSTP1 levels were detected to evaluate the GSH metabolism level by analyzing the GSH/GSSG ratio. In vivo experiments were performed to explore the effect of FOXA2/ETV4 on CRC progression, and the expression of related proteins was detected by western blot. ETV4 was highly expressed in CRC. Knocking down ETV4 suppressed CRC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) progression in vitro. ETV4 was abundant in the GSH metabolic pathway, and overexpression of ETV4 facilitated CRC malignant progression through activation of the GSH metabolism. In addition, in vitro cellular experiments and in vivo experiments in nude mice confirmed that FOXA2 transcriptionally activated ETV4. Knocking down FOXA2 repressed the malignant phenotype of CRC cells by suppressing GSH metabolism. These effects were reversed by overexpressing ETV4. Our results indicated that FOXA2 transcriptionally activates ETV4 to facilitate CRC malignant progression by modulating the GSH metabolic pathway. Targeting the FOXA2/ETV4 axis or GSH metabolism may be an effective approach for CRC treatment.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306874","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":"Pathway Gene Paralogues and Transcription Factors Differentially Associate with Contents of Picrosides in Tissues and Populations of a Medicinal Herb, Picrorhiza kurroa.","authors":"Roma Pandey, Anjali Kharb, Ashish Sharma, Hemant Sood, Rajinder Singh Chauhan","doi":"10.1007/s10528-024-10930-2","DOIUrl":"https://doi.org/10.1007/s10528-024-10930-2","url":null,"abstract":"<p><p>Picrorhiza kurroa is a valuable medicinal herb of Himalayan region, containing two major pharmacological iridoid glycosides: Picroside-I and Picroside-II, in addition to several other secondary metabolites. The metabolic diversity of P. kurroa may stem from the evolutionary processes attributed to pathway genes family expansion via gene duplication or splicing giving rise to paralogues which are further controlled by regulatory components. Occurrence of multiple pathway gene paralogues coupled with which TFs associate with paralogues in different genetic backgrounds (populations) in tissue-specific manner are still unresolved. Here, we unravelled possible correlations between TFs and gene paralogues across a range of P. kurroa accessions which might be contributing to differential contents of Picroside-I and Picroside-II in different tissues/organs. Characterization of shoots, roots, and stolons of eighty-five accessions of P. kurroa revealed significant variations for Picroside-I and Picroside-II contents. Comparative transcriptome analysis of shoot-derived transcriptome (PKSS), and root-derived transcriptome (PKSR) followed by their expression analysis in different P. kurroa accessions revealed TFs; PkWRKY71, PkWRKY12, PkNAC25, and PkMyb46 possibly regulate different gene paralogues. Genes encoding these putative TFs and pathway gene paralogues were further used to generate a robust co-expression network, thereby, uncovering their coordinated behaviour in association with Picroside-I and Picroside-II contents in shoots and roots, respectively. The outcome has provided potential leads, which through further functional validation can provide suitable targets, either for pathway engineering or as gene markers for selection of genetically superior populations of P. kurroa.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278423","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":"Prognostic Significance and Immune Landscape of an Efferocytosis-Related Gene Signature in Bladder Cancer.","authors":"Fuchun Zheng, Zhipeng Wang, Qianxi Dong, Sheng Li, Situ Xiong, Yuyang Yuan, Songhui Xu, Bin Fu","doi":"10.1007/s10528-024-10924-0","DOIUrl":"https://doi.org/10.1007/s10528-024-10924-0","url":null,"abstract":"<p><p>Bladder cancer poses a significant global health challenge, underscoring the imperative for precise prognostic instruments to advance patient care. Against the backdrop of efferocytosis's increasingly recognized role in cancer, this research endeavors to develop and authenticate a prognostic signature intricately linked to efferocytosis in bladder cancer. LASSO-COX regression analysis crafted an efferocytosis-related genes risk prognostic model, followed by the construction of a column chart. External validation sets confirmed the predictive accuracy of both the model and chart. Clinical, tumor microenvironment, drug sensitivity, and immunotherapy analyses were employed to comprehensively assess efferocytosis-related scores. The expression of TGFB3 key genes was validated via RT-PCR and western blotting. Further validation included Transwell, Wound healing, Colony formation, and EDU assays. We formulated and validated an efferocytosis-related genes risk model in bladder cancer, comprising 13 core genes. The risk model demonstrated autonomous prognostic significance in both univariate and multivariate Cox analyses. Following the multivariate analysis, we devised a nomogram. Moreover, by utilizing individual risk scores derived from this risk model, we successfully stratified patients into two discernible risk cohorts, unveiling noteworthy variances in immune infiltration profiles and responsiveness to immunotherapy. Notably, the model's key gene TGFB3 was validated through comprehensive experimental investigations, including Transwell assays for migration and invasion and Wound healing assays for motility on the T24 and BIU cell lines. This study has furnished innovative perspectives on an efferocytosis-related prognostic signature, elucidating the prognosis and immune milieu intricacies in patients with bladder cancer.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306873","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":"Matrix Metalloproteinases -2 and -9, Vascular Endothelial Growth Factor, Basic Fibroblast Growth Factor and CD105- Micro-Vessel Density are Predictive Markers of Non-Muscle Invasive Bladder Cancer and Muscle Invasive Bladder Cancer Subtypes.","authors":"Rohit Siddhartha, Apul Goel, Atin Singhai, Minal Garg","doi":"10.1007/s10528-024-10921-3","DOIUrl":"https://doi.org/10.1007/s10528-024-10921-3","url":null,"abstract":"<p><p>Matrix metalloproteinases (MMPs) are involved in extracellular matrix (ECM) remodeling during embryogenesis, wound healing and tumor development. Aberrant expressions and activation of MMP-2 and MMP-9 are examined as one of the major attributes acquired by tumor neoangiogenic markers including vascular endothelial growth factor (VEGF), basic growth factor (bFGF) and CD105-microvessel density (CD105-MVD) during bladder tumorigenesis. The present study examined the levels of MMP-2, MMP-9, VEGF, bFGF and CD105 to elucidate the relationship among them and associated clinical features in the given cohort of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) patients. Real time-quantitative PCR was done to examine the gene expressions of MMP-2, MMP-9, VEGF, bFGF and CD105 in 70 NMIBC and 40 MIBC patients. Western blotting and immunohistochemical staining were done to check their immunolevels followed by statistical analyses of their expressions with patients' demographic variables. Scanning electron microscopic (SEM) studies were done in representative non-muscle and muscle invasive tumor specimens to elucidate the tumor vasculature and extent of neoangiogenesis. The study reported an increase in gene expression and immunolevels of MMP-2, MMP-9, VEGF, bFGF and CD105-MVD with tumor stage and tumor grade. Statistical studies examined the relevant associations of their expressions with tumor stage, tumor grade, tumor size, tumor type, and tobacco chewing/smoking history of patients. SEM studies revealed marked differences in the vascular architecture and their spatial distribution indicated by increase in vascular density, vascular sprout proliferation and new blood vessel formation with tumor stage and tumor grade. The discriminatory ability of MMP-2, MMP-9, VEGF, bFGF and CD105-MVD in the diagnosis of NMIBC and MIBC was confirmed by ROC curve analysis which revealed the high sensitivity and low specificity of these markers in a given cohort of patients. Observed positive correlations of angiogenic markers with MMP-2 and MMP-9 in the given cohorts of NMIBC and MIBC patients explain their possible effects on bladder tumorigenesis via vascular angiogenesis. Cox regression (univariate and multivariate) and Kaplan-Meier along with log-rank survival analysis examined the strong expressions of these markers as the predictive indicators of poor survival probability (OS, RFS, PFS, and CSS) in 52 NMIBC and 36 MIBC patients. Significant associations of expressions of MMP-2, MMP-9, VEGF, bFGF and CD105-MVD with clinical variables emphasized their significance in diagnosis of NMIBC and MIBC patients. Survival analysis identified these markers as the independent prognosticators of poor survival of NMIBC and MIBC patients. Nevertheless, multi-center analysis is required to validate their importance in the clinical management of NMIBC and MIBC patients.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278422","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":"Single-cell RNA Sequencing Demonstrates the Heterogeneity of Different Molecular Subtypes in Gastric Cancer.","authors":"Ming Ren, Hongyan Ma, Lijia Guo, Yuqing Liu, Li Wang, Shaoting Wei","doi":"10.1007/s10528-024-10922-2","DOIUrl":"https://doi.org/10.1007/s10528-024-10922-2","url":null,"abstract":"<p><p>Gastric cancer is a disease with high molecular and phenotypic heterogeneity. We integrated 119,878 cells from different molecular subtypes of gastric cancer and conducted comprehensive analysis. We found that patients with different molecular subtypes of gastric cancer showed significantly different cell composition heterogeneity, and the proportion of plasma cells was higher in GS tumors. After that, we constructed subtype-specific lncRNA-gene regulatory networks and identified subtype-specific lncRNA-related biological functions and pathways. Our study found that MALAT1-CTNNB1 regulatory pairs existed in CIN subtype, XIST-KLF2 regulatory pairs existed in GS subtype, and KCNQ1OT1-CCND2 regulatory pairs existed in MSI subtype. Next, we identified subtype-specific lncRNAs associated with prognosis. Our study found that NEAT1 could be used as prognostic factors for CIN tumors, and MALAT1 and XIST could be used as prognostic factors for GS tumors. In addition, we characterized the interactions between tumor cells and tumor microenvironment cells in different molecular subtypes of gastric cancer. In conclusion, we revealed the heterogeneity among different TCGA molecular subtypes of gastric cancer at the single-cell level, and identified the subtype-specific lncRNAs associated with prognosis. Our study may contribute to the in-depth understanding of the heterogeneity of gastric cancer and the prediction of patient prognosis.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278425","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":"Integration Analysis of miRNA Circulating Expression Following Cerebellar Transcranial Direct Current Stimulation in Patients with Ischemic Stroke.","authors":"Xiaomin Pang, Fang Xiao, Tianqing Zheng, Liren Zhao, Xiaorong Ge, Shaojun Xie, Zhao Zhang, Ning Xu, Zongyong Wei, Zhanhong Xiao","doi":"10.1007/s10528-024-10912-4","DOIUrl":"https://doi.org/10.1007/s10528-024-10912-4","url":null,"abstract":"<p><p>The aim of this study was to explore the molecular mechanisms underlying cerebellar transcranial direct current stimulation (ctDCS) as a rehabilitation intervention for patients with ischemic stroke, focusing on the role of microRNAs (miRNAs). Whole-transcriptome sequencing was employed to obtain circulating expression profiles of miRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and mRNAs in patients with ischemic stroke before and after 3-week ctDCS. miRanda software was used to predict the target genes of miRNAs, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to identify biological functions and signaling pathways. Subsequently, competing endogenous RNA (ceRNA) regulatory networks comprising circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA interactions were constructed. Key miRNAs in blood samples were validated through quantitative RT-PCR. In total, 43 miRNAs, 807 lncRNAs, 1,111 circRNAs, and 201 mRNAs were differentially expressed after ctDCS compared with before ctDCS. Bioinformatics analyses revealed significant enrichment of target genes regulated by differentially expressed miRNAs across multiple biological pathways. CeRNA regulatory networks implied that several miRNAs were closely related to the ctDCS. Among them, hsa-miR-181a-5p, hsa-miR-224-5p, and hsa-miR-340-3p showed significantly downregulated expression levels as confirmed by qRT-PCR. This study conducted the first-ever assessment of miRNA expression patterns in patients with ischemic stroke undergoing ctDCS. The findings revealed that ctDCS induces alterations in miRNA levels, suggesting their potential utility as therapeutic markers.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278421","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":"Association of MTHFR rs9651118 and TYMS rs2790 Polymorphisms with Risk of Cancers: A Case-Control Study and Meta-analysis.","authors":"Weiguang Zhou, Yingxuan Xiao, Yifan Jiang, Aoxiang Zou, Jiangyi Ruan, Xianhong Feng, Jing Li, Bifeng Chen","doi":"10.1007/s10528-024-10929-9","DOIUrl":"https://doi.org/10.1007/s10528-024-10929-9","url":null,"abstract":"<p><p>Recently, rs9651118 in the MTHFR gene and rs2790 in the TYMS gene have been repeatedly studied for their contribution to cancer risk. However, the results remain conflicting rather than conclusive. Therefore, we here conducted a replication case-control study and a meta-analysis to comprehensively examine the contribution of rs9651118 and rs2790 to cancer risk. A total of 1727 patients with colorectal/gastric/liver (787/460/480) cancer and 800 healthy controls were recruited, and the Sanger sequencing was applied to genotype rs9651118 and rs2790. Besides, a total of 23 eligible studies were included in the following meta-analysis. After Bonferroni correction, the results of case-control study suggested that significant associations between rs9651118 and colorectal cancer (CRC) risk, rs9651118 and gastric cancer (GC) risk, and rs2790 and liver cancer (LC) risk were identified in Hubei Chinese population. The results of meta-analysis indicated that after Bonferroni correction, both rs9651118 and rs2790 were significantly associated with total cancer risk especially in Asian population and based on Sanger sequencing method, rs9651118 was significantly associated with breast cancer (BC) risk, and rs2790 was significantly associated with the risk of CRC and GC. In conclusion, the present findings revealed that the MTHFR gene rs9651118 may participate in the risk of total cancer (especially BC) in Asian population, and the TYMS gene rs2790 may be associated with the risk of total cancer (especially CRC) in Asian population and also the risk of GC in total population.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278420","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":"Proteomic Analysis Provides a New Sight Into the CRABP1 Expression in the Pathogenesis of Hirschsprung Disease","authors":"Lingyun Bu, Lingxiao He, Xiaoqing Wang, Guoqiang Du, Rongde Wu, Wei Liu","doi":"10.1007/s10528-024-10913-3","DOIUrl":"https://doi.org/10.1007/s10528-024-10913-3","url":null,"abstract":"<p>Hirschsprung’s disease (HSCR) is the most common developmental disorder of the enteric nervous system and its etiology and pathogenesis remain largely unknown. This study aims to identify the differential proteomic patterns linked to the occurrence and development of Hirschsprung disease in colonic tissues. Biopsies were obtained from the aganglionic colon in human HSCR and the corresponding ganglionic colon segments for direct quantitative determination of the data-independent acquisition (DIA) followed by bioinformatics analysis. The differentially expressed main proteins were confirmed by Western blot and immunostaining. A total of 5832 proteins were identified in human colon tissues. Among them, 97 differentially expressed proteins (DEP) with fold change (FC) &gt; 1.2 were screened, including 18 upregulated proteins and 79 downregulated proteins, and GO and KEGG enrichment analyses were performed on differential proteins. By comparing down-regulated proteins with highly connected protein nodes in the PPI network with those related to intracellular metabolic processes in the above analysis, we identified cellular retinoic acid binding protein 1(CRABP1). Its expression was verified in the aganglionic part of the colon by western blotting in an expanded sample set (<i>P</i> = 0.0031). The immunostaining results revealed that CRABP1 was highly expressed in the myenteric plexus ganglion in ganglionic colons compared to aganglionic segments (<i>P</i> = 0.0004). This study demonstrated the down-regulation of CRABP1 in the aganglionic hindgut of HSCR, which could provide potential markers or promising new candidate actors for the pathogenesis of HSCR.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260487","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}