Experimental and molecular pathology最新文献

{"title":"DNA methylation of HOX genes and its clinical implications in cancer","authors":"Xin Hu ,&nbsp;Yong Wang ,&nbsp;Xiaoyu Zhang ,&nbsp;Chensheng Li ,&nbsp;Xikun Zhang ,&nbsp;Dongxia Yang ,&nbsp;Yuanyuan Liu ,&nbsp;Lianlian Li","doi":"10.1016/j.yexmp.2023.104871","DOIUrl":"10.1016/j.yexmp.2023.104871","url":null,"abstract":"<div><p>Homeobox (HOX) genes encode highly conserved transcription factors that play vital roles in embryonic development. DNA methylation is a pivotal regulatory epigenetic signaling mark responsible for regulating gene expression. Abnormal DNA methylation is largely associated with the aberrant expression of HOX genes, which is implicated in a broad range of human diseases, including cancer. Numerous studies have clarified the mechanisms of DNA methylation in both physiological and pathological processes. In this review, we focus on how DNA methylation regulates HOX genes and briefly discuss drug development approaches targeting these mechanisms.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"134 ","pages":"Article 104871"},"PeriodicalIF":3.6,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10241404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of the critical role of vitamin D axis on the immune system","authors":"Gholamreza Daryabor ,&nbsp;Nasser Gholijani ,&nbsp;Fatemeh Rezaei Kahmini","doi":"10.1016/j.yexmp.2023.104866","DOIUrl":"10.1016/j.yexmp.2023.104866","url":null,"abstract":"<div><p>In recent years, the physiological and molecular functions of vitamin D (Vit-D) have been deeply investigated. At first, Vit-D was considered a regulator of mineral and skeletal homeostasis. However, due to the extensive-expression pattern of Vit-D receptor (VDR) in almost every non-skeletal cell, Vit-D is considered mainly a multifunctional agent with broad effects on various tissues, notably the immune system. The expression of VDR in immune cells such as dendritic cells, monocyte/macrophage, neutrophils, B cells and T cells has been well demonstrated. Besides, such immune cells are capable of metabolizing the active form of Vit-D which means that it can module the immune system in both paracrine and autocrine manners. Vit-D binding protein (DBP), that regulates the levels and homeostasis of Vit-D, is another key molecule capable of modulating the immune system. Recent studies indicate that dysregulation of Vit-D axis, variations in the DBP and VDR genes, and Vit-D levels might be risk factors for the development of autoimmune disease. Here, the current evidence regarding the role of Vit-D axis on the immune system, as well as its role in the development of autoimmune disease will be clarified. Further insight will be given to those studies that investigated the association between single nucleotide polymorphisms of DBP and VDR genes with autoimmune disease susceptibility.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"132 ","pages":"Article 104866"},"PeriodicalIF":3.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10650329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of human umbilical cord blood-derived mast cells using high-throughput expression profiling and next-generation knowledge discovery platforms","authors":"Sherin Bakhashab ,&nbsp;Ghalya H. Banafea ,&nbsp;Farid Ahmed ,&nbsp;Haneen Alsehli ,&nbsp;Huda F. AlShaibi ,&nbsp;Nadia Bagatian ,&nbsp;Ohoud Subhi ,&nbsp;Kalamegam Gauthaman ,&nbsp;Mahmood Rasool ,&nbsp;Hans-Juergen Schulten ,&nbsp;Peter Natesan Pushparaj","doi":"10.1016/j.yexmp.2023.104867","DOIUrl":"10.1016/j.yexmp.2023.104867","url":null,"abstract":"<div><p>Mast cells (MCs) are tissue-resident innate immune cells that express the high-affinity receptor for immunoglobulin E and are responsible for host defense and an array of diseases related to immune system. We aimed in this study to characterize the pathways and gene signatures of human cord blood-derived MCs (hCBMCs) in comparison to cells originating from CD34⁻ progenitors using next-generation knowledge discovery methods. CD34⁺ cells were isolated from human umbilical cord blood using magnetic activated cell sorting and differentiated into MCs with rhIL-6 and rhSCF supplementation for 6–8 weeks. The purity of hCBMCs was analyzed by flow cytometry exhibiting the surface markers CD117⁺CD34⁻CD45⁻CD23⁻FcεR1α^dim. Total RNA from hCBMCs and CD34⁻ cells were isolated and hybridized using microarray. Differentially expressed genes were analyzed using iPathway Guide and Pre-Ranked Gene Set Enrichment Analysis. Next-generation knowledge discovery platforms revealed MC-specific gene signatures and molecular pathways enriched in hCBMCs and pertain the immunological response repertoire.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"132 ","pages":"Article 104867"},"PeriodicalIF":3.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10651884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulation of circ-HIPK3, circ-PVT1, miR-25, and miR-149 in radiosensitivity of breast cancer","authors":"Elahe Abdollahi,&nbsp;Hossein Mozdarani","doi":"10.1016/j.yexmp.2023.104865","DOIUrl":"10.1016/j.yexmp.2023.104865","url":null,"abstract":"<div><p>Assessing the radiosensitivity of cells before administering radiation therapy (RT) to individuals diagnosed with breast cancer (BC) can facilitate the selection of appropriate treatment regimens and minimize the incidence of adverse side effects in patients undergoing radiation exposure.</p><p>In this research, blood samples were obtained from 60 women who had been diagnosed with Invasive Ductal Carcinoma (IDC) Breast Cancer. The average age of the patients was 47 ± 9.93. Additionally, the study incorporated 20 healthy women, with an average age of 44.43 ± 6.7. A standard G2 assay was conducted to predict the cellular response to radiation. Out of the 60 samples, the G2 assay identified 20 patients with breast cancer who exhibited radiosensitivity. Hence, molecular investigations were ultimately conducted on two equivalent cohorts comprising 20 subjects each, one with and the other without cellular radiosensitivity. The expression levels of miR-149, miR-25, circ-PVT1, and circ-HIPK3 in peripheral blood mononuclear cells (PBMCs) were evaluated using quantitative polymerase chain reaction (qPCR). Receiver Operating Characteristic (ROC) curves were used to evaluate the sensitivity and specificity of the RNAs. An analysis using binary logistic regression was performed to investigate the relationship between RNAs and both BC and cellular radiosensitivity (CR) in patients with BC.</p><p>The findings revealed a significant upregulation of Circ-HIPK3 and circ-PVT1 in individuals diagnosed with BC. The levels of Circ-HIPK3 and Circ-PVT1 were found to be directly associated with CR in BC patients. The analysis of the ROC curve demonstrated that circ-HIPK3 and circ-PVT1 exhibit favorable specificity and sensitivity in accurately predicting both BC and CR in patients with BC. The findings from the binary logistic regression analysis demonstrated that circ-HIPK3 and circ-PVT1 were effective predictors of both BC and CR. The ROC curve and binary logistic regression analyses provide evidence that miR-25 is a reliable predictor for BC patients exclusively.</p><p>Our research has demonstrated that circ-HIPK3, circ-PVT1, and miR-25 may be involved in BC regulatory processes. The circular RNAs Circ-HIPK3 and circ-PVT1, as well as miR-25, among other significant biomarkers, could potentially serve as promising biomarkers for predicting BC. Furthermore, Circ-HIPK3 and circ-PVT1 have the potential to serve as biomarkers for predicting CR in BC patients.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"132 ","pages":"Article 104865"},"PeriodicalIF":3.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The biogenesis, biological functions and modification of Circular RNAs","authors":"Sen Liu ,&nbsp;Xiang Yu Guo ,&nbsp;Qing Juan Shang ,&nbsp;Peng Gao","doi":"10.1016/j.yexmp.2023.104861","DOIUrl":"10.1016/j.yexmp.2023.104861","url":null,"abstract":"<div><p>Circular RNAs are covalently closed and non-coding in eukaryotes, which have tissue- specific and temporal-specific expression patterns whose biogenesis is regulated by transcription and splicing. Most circular RNAs are localized in the cytoplasm. The sequences and protein-binding elements of circular RNAs facilitate circular RNAs in exerting biological functions through complementary base pairing, regulating protein function or self-translation. Recent studies have revealed that N6-Methyladenosine (m6A), a prevalent post-transcriptional modification, can affect the translation, localization, and degradation of circular RNAs. Cutting-edge research into circular RNAs have benefitted from the development of high-throughput sequencing technology. Furthermore, the expansion of novel research methods has promoted progress into circular RNA research.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"131 ","pages":"Article 104861"},"PeriodicalIF":3.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9630451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokeratin 20 expression is linked to stage progression and to poor prognosis in advanced (pT4) urothelial carcinoma of the bladder","authors":"Paul Giacomo Bruch ,&nbsp;Henning Plage ,&nbsp;Sebastian Hofbauer ,&nbsp;Kira Kornienko ,&nbsp;Sarah Weinberger ,&nbsp;Florian Roßner ,&nbsp;Simon Schallenberg ,&nbsp;Martina Kluth ,&nbsp;Maximilian Lennartz ,&nbsp;Niclas C. Blessin ,&nbsp;Andreas H. Marx ,&nbsp;Henrik Samtleben ,&nbsp;Margit Fisch ,&nbsp;Michael Rink ,&nbsp;Marcin Slojewski ,&nbsp;Krystian Kaczmarek ,&nbsp;Thorsten Ecke ,&nbsp;Steffen Hallmann ,&nbsp;Stefan Koch ,&nbsp;Nico Adamini ,&nbsp;Sefer Elezkurtaj","doi":"10.1016/j.yexmp.2023.104860","DOIUrl":"10.1016/j.yexmp.2023.104860","url":null,"abstract":"<div><p>Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on &gt;2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; <em>p</em> = 0.0006) but was lower in muscle-invasive (pT2–4) carcinomas (51.1% in all pTa vs. 29.6% in pT2–4; <em>p</em> &lt; 0.0001). Within pT2–4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p &lt; 0.0001 each) and to venous invasion (<em>p</em> = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2–4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (<em>p</em> = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (<em>p</em> &lt; 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20−/GATA3+) and basal/squamous (CK20−/GATA3-) in pT4 urothelial carcinomas (<em>p</em> = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"131 ","pages":"Article 104860"},"PeriodicalIF":3.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9627189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of BRCA1 and BRCA2 alternative splicing in predisposition to ovarian cancer","authors":"Anna Jasiak ,&nbsp;Magdalena Koczkowska ,&nbsp;Maciej Stukan ,&nbsp;Dariusz Wydra ,&nbsp;Wojciech Biernat ,&nbsp;Ewa Izycka-Swieszewska ,&nbsp;Kamil Buczkowski ,&nbsp;Michael R. Eccles ,&nbsp;Logan Walker ,&nbsp;Bartosz Wasag ,&nbsp;Magdalena Ratajska","doi":"10.1016/j.yexmp.2023.104856","DOIUrl":"10.1016/j.yexmp.2023.104856","url":null,"abstract":"<div><h3>Background</h3><p>The mRNA splicing is regulated on multiple levels, resulting in the proper distribution of genes' transcripts in each cell and maintaining cell homeostasis. At the same time, the expression of alternative transcripts can change in response to underlying genetic variants, often missed during routine diagnostics.</p></div><div><h3>Aim</h3><p>The main aim of this study was to define the frequency of aberrant splicing in <em>BRCA1</em> and <em>BRCA2</em> genes in blood RNA extracted from ovarian cancer patients who were previously found negative for the presence of pathogenic alterations in the 25 most commonly analysed ovarian cancer genes, including <em>BRCA1</em> and <em>BRCA2</em>.</p></div><div><h3>Material and methods</h3><p>Frequency and spectrum of splicing alterations in <em>BRCA1</em> and <em>BRCA2</em> genes were analysed in blood RNA from 101 ovarian cancer patients and healthy controls (80 healthy women) using PCR followed by gel electrophoresis and Sanger sequencing. The expression of splicing events was examined using RT-qPCR.</p></div><div><h3>Results</h3><p>We did not identify any novel, potentially pathogenic splicing alterations. Nevertheless, we detected six naturally occurring transcripts, named <em>BRCA1ΔE9-10</em>, <em>BRCA1ΔE11</em>, <em>BRCA1ΔE11q</em>, and <em>BRCA2ΔE3</em>, <em>BRCA2ΔE12</em> and <em>BRCA2ΔE17-18</em> of which three (<em>BRCA1ΔE11q</em>, <em>BRCA1ΔE11</em> and <em>BRCA2ΔE3</em>) were significantly higher expressed in the ovarian cancer cohort than in healthy controls (<em>p</em> ≤ 0.0001).</p></div><div><h3>Conclusions</h3><p>This observation indicates that the upregulation of selected naturally occurring transcripts can be stimulated by non-genetic mechanisms and be a potential systemic response to disease progression and/or treatment. However, this hypothesis requires further examination.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"130 ","pages":"Article 104856"},"PeriodicalIF":3.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9309778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amplicon-based NGS test for assessing MLH1 promoter methylation and its correlation with BRAF mutation in colorectal cancer patients","authors":"Sara Iolanda Oliveira da Silva ,&nbsp;Tabata Alves Domingos ,&nbsp;Bruna Elisa Catin Kupper ,&nbsp;Louise De Brot ,&nbsp;Samuel Aguiar Junior ,&nbsp;Dirce Maria Carraro ,&nbsp;Giovana Tardin Torrezan","doi":"10.1016/j.yexmp.2023.104855","DOIUrl":"10.1016/j.yexmp.2023.104855","url":null,"abstract":"<div><p>Detecting <em>MLH1</em> promoter methylation is highly relevant to differentiate between possible Lynch syndrome patients or patients with sporadic causes of MLH1/PMS2 deficiency in colorectal (CRC) and endometrial cancers. Here, we aimed to develop a test for assessing <em>MLH1</em> promoter methylation based in next generation sequencing (NGS), and to evaluate the concordance of <em>MLH1</em> methylation and <em>BRAF</em>-V600 mutation status in CRC. For that, we performed a series of experiments with DNA from tumor, saliva and commercial control samples and our in house developed amplicon-based NGS test. In patients' samples, <em>MLH1</em> methylation above 10% was only observed in tumors with MLH1/PMS2 loss. We confirmed the reproducibility and accuracy of <em>MLH1</em> promoter analysis performing a serial dilution experiment with completely methylated and unmethylated control DNAs and a comparison between two NGS platforms (Ion Proton and Illumina). In MLH1/PMS2 deficient tumors, the <em>MLH1</em> methylation status was concordant with the <em>BRAF</em> mutation status in 90% (18/20) of the cases. Our amplicon-based NGS test showed a great sensitivity and specificity for detecting <em>MLH1</em> methylation in CRC samples, with a high agreement with the evaluation of <em>BRAF</em> mutation. This simple and affordable test could be used as a reflex test to identify patients with sporadic causes of MLH1/PMS2 deficiency in CRC, aiding to genetic test referral and identification of Lynch syndrome patients.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"130 ","pages":"Article 104855"},"PeriodicalIF":3.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “ Probucol via inhibition of NHE1 attenuates LPS-accelerated atherosclerosis and promotes plaque stability in vivo” [Experimental and Molecular Pathology 96/2 (2014) 250–256]","authors":"Li Jian-Fei ,&nbsp;Chen Song ,&nbsp;Feng Jun-Duo ,&nbsp;Zhang Ming-Yu ,&nbsp;Liu Xiao-Xia","doi":"10.1016/j.yexmp.2022.104847","DOIUrl":"10.1016/j.yexmp.2022.104847","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"129 ","pages":"Article 104847"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9170300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression analysis of hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in renal cell carcinoma","authors":"Elham Mohammadisoleimani ,&nbsp;Zahra Firoozi ,&nbsp;Mohammad Mehdi Naghizadeh ,&nbsp;Ali Ghanbari Asad ,&nbsp;Anahita Jafari ,&nbsp;Mohammad Hosein Pourjafarian ,&nbsp;Ali Ariafar ,&nbsp;Hosein Mansoori ,&nbsp;Hassan Dastsooz ,&nbsp;Hani Sabaie ,&nbsp;Shahryar Zeighami ,&nbsp;Yaser Mansoori","doi":"10.1016/j.yexmp.2022.104848","DOIUrl":"10.1016/j.yexmp.2022.104848","url":null,"abstract":"<div><p>Renal cell carcinoma (RCC) is a prevalent heterogeneous kidney cancer. So far, different genes have been reported for RCC development. However, its particular molecular mechanism remains unclear. Circular RNAs (circRNAs), a class of non-coding RNAs, are involved in numerous biological processes in different malignancies such as RCC. This study aims to assess the expression and underlying mechanism of four circRNAs (hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, hsa_circ_0006990) with possible new roles in RCC. In the experimental step, we investigated the expression of these four circRNAs in our RCC samples using quantitative real-time polymerase chain reaction. In the bioinformatics step, the differential expressed mRNAs (DEmRNAs), and miRNAs (DEmiRNAs) were obtained from the GEO datasets using the GEO2R tool. A protein-protein interaction network was constructed using the STRING database, and hub genes were identified by Cytoscape. Molecular pathways associated with hub genes were detected using KEGG pathway enrichment analysis. Then, we utilized the ToppGene database to detect the relationships between DEmiRNAs and hub genes. Furthermore, interactions between circRNAs and DEmiRNAs were predicted by the StarBase and circinteractome databases. Finally, a circRNA-DEmiRNA-hub gene triple network was constructed. Our results revealed that the expression of hsa_circ_0020397, hsa_circ_0005986, and hsa_circ_0006990 was downregulated in RCC tissues. Moreover, these circRNAs had a significantly lower expression in patients with a history of kidney disease. Furthermore, hsa_circ_0003028 and hsa_circ_0006990 showed higher expression in the tumor of participants with Lymphovascular/perineural invasion and oncocytoma type, respectively. Based on bioinformatic results, 15 circRNA-DEmiRNA-hub gene ceRNA regulatory axes were predicted, which included three hub genes, five miRNAs, and four selected circRNAs. In conclusion, the current work is the first to emphasize the expression of the hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in RCC patients presents a novel perspective on the molecular processes underlying the pathogenic mechanisms of RCC.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"129 ","pages":"Article 104848"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10761001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}