Background: The genetic factors and pathogenesis of idiopathic dilated cardiomyopathy-induced heart failure (IDCM-HF) have not been understood thoroughly; there is a lack of specific diagnostic markers and treatment methods for the disease. Hence, we aimed to identify the mechanisms of action at the molecular level and potential molecular markers for this disease.
Methods: Gene expression profiles of IDCM-HF and non-heart failure (NF) specimens were acquired from the database of Gene Expression Omnibus (GEO). We then identified the differentially expressed genes (DEGs) and analyzed their functions and related pathways by using "Metascape". Weighted gene co-expression network analysis (WGCNA) was utilized to search for key module genes. Candidate genes were identified by intersecting the key module genes identified via WGCNA with DEGs and further screened via the support vector machine-recursive feature elimination (SVM-RFE) method and the least absolute shrinkage and selection operator (LASSO) algorithm. At last, the biomarkers were validated and evaluated the diagnostic efficacy by the area under curve (AUC) value and further confirmed the differential expression in the IDCM-HF and NF groups using an external database.
Results: We detected 490 genes exhibiting differential expression between IDCM-HF and NF specimens from the GSE57338 dataset, with most of them being concentrated in the extracellular matrix (ECM) of cells related to biological processes and pathways. After screening, 13 candidate genes were identified. Aquaporin 3 (AQP3) and cytochrome P450 2J2 (CYP2J2) showed high diagnostic efficacy in the GSE57338 and GSE6406 datasets, respectively. In comparison to the NF group, AQP3 was significantly down-regulated in the IDCM-HF group, while CYP2J2 was significantly up-regulated.
Conclusion: As far as we know, this is the first study that combines WGCNA and machine learning algorithms to screen for potential biomarkers of IDCM-HF. Our findings suggest that AQP3 and CYP2J2 could be used as novel diagnostic markers and treatment targets of IDCM-HF.
背景:特发性扩张型心肌病诱发心力衰竭(IDCM-HF)的遗传因素和发病机制尚未完全了解;目前缺乏特异性的诊断标记物和治疗方法。因此,我们的目的是在分子水平上确定作用机制和潜在的分子标记。方法:从Gene expression Omnibus (GEO)数据库中获取IDCM-HF和非心力衰竭(NF)标本的基因表达谱。利用“meta - scape”软件对差异表达基因(differential expression genes, deg)进行鉴定,分析其功能和相关途径。采用加权基因共表达网络分析(Weighted gene co-expression network analysis, WGCNA)搜索关键模块基因。将WGCNA识别出的关键模块基因与deg相交,确定候选基因,并通过支持向量机递归特征消除(SVM-RFE)方法和最小绝对收缩选择算子(LASSO)算法进行筛选。最后,通过曲线下面积(area under curve, AUC)值对生物标志物进行验证和诊断效能评估,并利用外部数据库进一步确认IDCM-HF组和NF组的差异表达。结果:我们从GSE57338数据集中检测到490个基因在IDCM-HF和NF样本中表现出差异表达,其中大多数基因集中在与生物过程和途径相关的细胞外基质(ECM)中。经筛选,共鉴定出13个候选基因。水通道蛋白3 (AQP3)和细胞色素P450 2J2 (CYP2J2)分别在GSE57338和GSE6406数据集中显示出较高的诊断效能。与NF组比较,IDCM-HF组AQP3显著下调,CYP2J2显著上调。结论:据我们所知,这是第一个结合WGCNA和机器学习算法筛选IDCM-HF潜在生物标志物的研究。提示AQP3和CYP2J2可作为IDCM-HF新的诊断标记物和治疗靶点。
{"title":"Identification of Biomarkers Associated with Heart Failure Caused by Idiopathic Dilated Cardiomyopathy Using WGCNA and Machine Learning Algorithms.","authors":"Mengyi Sun, Linping Li","doi":"10.1155/2023/2250772","DOIUrl":"https://doi.org/10.1155/2023/2250772","url":null,"abstract":"<p><strong>Background: </strong>The genetic factors and pathogenesis of idiopathic dilated cardiomyopathy-induced heart failure (IDCM-HF) have not been understood thoroughly; there is a lack of specific diagnostic markers and treatment methods for the disease. Hence, we aimed to identify the mechanisms of action at the molecular level and potential molecular markers for this disease.</p><p><strong>Methods: </strong>Gene expression profiles of IDCM-HF and non-heart failure (NF) specimens were acquired from the database of Gene Expression Omnibus (GEO). We then identified the differentially expressed genes (DEGs) and analyzed their functions and related pathways by using \"Metascape\". Weighted gene co-expression network analysis (WGCNA) was utilized to search for key module genes. Candidate genes were identified by intersecting the key module genes identified via WGCNA with DEGs and further screened via the support vector machine-recursive feature elimination (SVM-RFE) method and the least absolute shrinkage and selection operator (LASSO) algorithm. At last, the biomarkers were validated and evaluated the diagnostic efficacy by the area under curve (AUC) value and further confirmed the differential expression in the IDCM-HF and NF groups using an external database.</p><p><strong>Results: </strong>We detected 490 genes exhibiting differential expression between IDCM-HF and NF specimens from the GSE57338 dataset, with most of them being concentrated in the extracellular matrix (ECM) of cells related to biological processes and pathways. After screening, 13 candidate genes were identified. Aquaporin 3 (AQP3) and cytochrome P450 2J2 (CYP2J2) showed high diagnostic efficacy in the GSE57338 and GSE6406 datasets, respectively. In comparison to the NF group, AQP3 was significantly down-regulated in the IDCM-HF group, while CYP2J2 was significantly up-regulated.</p><p><strong>Conclusion: </strong>As far as we know, this is the first study that combines WGCNA and machine learning algorithms to screen for potential biomarkers of IDCM-HF. Our findings suggest that AQP3 and CYP2J2 could be used as novel diagnostic markers and treatment targets of IDCM-HF.</p>","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9767285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study searched for aging-related genes (ARGs) to predict the prognosis of patients with cervical cancer (CC). All data were obtained from Molecular Signatures Database, Cancer Genome Atlas, Gene Expression Integration, and Genotype Organization Expression. The R software was used to screen out the differentially expressed ARGs (DE-ARGs) between CC and normal tissues. A protein-protein interaction network was established by the DE-ARGs. The univariate and multivariate Cox regression analyses were conducted on the first extracted Molecular Complex Detection component, and a prognostic model was constructed. The prognostic model was further validated in the testing set and GSE44001 dataset. Prognosis was analyzed by Kaplan-Meier curves, and accuracy of the prognostic model was assessed by receiver operating characteristic area under the curve analysis. An independent prognostic analysis of risk score and some clinicopathological factors of CC was also performed. The copy-number variant (CNV) and single-nucleotide variant (SNV) of prognostic ARGs were analyzed by the BioPortal database. A clinical practical nomogram was established to predict individual survival probability. Finally, we carried out cell experiment to further verify the prognostic model. An eight-ARG prognostic signature for CC was constructed. High-risk CC patients had significantly shorter overall survival than low-risk patients. The receiver operating characteristic (ROC) curve validated the good performance of the signature in survival prediction. The Figo_stage and risk score served as independent prognostic factors. The eight ARGs mainly enriched in growth factor regulation and cell cycle pathway, and the deep deletion of FN1 was the most common CNV. An eight-ARG prognostic signature for CC was successfully constructed.
{"title":"Eight Aging-Related Genes Prognostic Signature for Cervical Cancer.","authors":"Meilin Yin, Yanhua Weng","doi":"10.1155/2023/4971345","DOIUrl":"https://doi.org/10.1155/2023/4971345","url":null,"abstract":"<p><p>This study searched for aging-related genes (ARGs) to predict the prognosis of patients with cervical cancer (CC). All data were obtained from Molecular Signatures Database, Cancer Genome Atlas, Gene Expression Integration, and Genotype Organization Expression. The R software was used to screen out the differentially expressed ARGs (DE-ARGs) between CC and normal tissues. A protein-protein interaction network was established by the DE-ARGs. The univariate and multivariate Cox regression analyses were conducted on the first extracted Molecular Complex Detection component, and a prognostic model was constructed. The prognostic model was further validated in the testing set and GSE44001 dataset. Prognosis was analyzed by Kaplan-Meier curves, and accuracy of the prognostic model was assessed by receiver operating characteristic area under the curve analysis. An independent prognostic analysis of risk score and some clinicopathological factors of CC was also performed. The copy-number variant (CNV) and single-nucleotide variant (SNV) of prognostic ARGs were analyzed by the BioPortal database. A clinical practical nomogram was established to predict individual survival probability. Finally, we carried out cell experiment to further verify the prognostic model. An eight-ARG prognostic signature for CC was constructed. High-risk CC patients had significantly shorter overall survival than low-risk patients. The receiver operating characteristic (ROC) curve validated the good performance of the signature in survival prediction. The Figo_stage and risk score served as independent prognostic factors. The eight ARGs mainly enriched in growth factor regulation and cell cycle pathway, and the deep deletion of FN1 was the most common CNV. An eight-ARG prognostic signature for CC was successfully constructed.</p>","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10860890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan-Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration-approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.
低级别胶质瘤(LGG)是最常见的颅内恶性肿瘤,容易发展为高级别胶质瘤并增加耐药性。细胞旁凋亡被定义为一种非凋亡形式的程序性细胞死亡,它逐渐被关注于胶质瘤患者,以开发治疗方案。然而,细胞凋亡在LGG中的具体作用及其相关性尚不清楚。在本研究中,我们首先建立了新的LGG患者基于眩晕的预后模型。我们从The Cancer Genome Atlas数据库中获取LGG患者的相关数据,通过一致聚类分析,我们发现LGG患者可以根据paraptosis分为三个不同的聚类。通过最小绝对收缩和选择算子回归分析及多变量Cox回归分析,鉴定出10个凋亡相关基因(PRG)特征(CDK4、TNK2、DSTYK、CDKN3、CCR4、CASP9、HSPA5、RGR、LPAR1、PDCD6IP),成功将LGG患者划分为高、低风险亚组。Kaplan-Meier分析和时间相关的受者操作特征显示,预测总生存期(OS)的性能非常高。利用中国胶质瘤基因组图谱和基因表达综合数据库对平行结果进行了再现和验证。独立预后分析和nomogram构建提示风险评分可以作为预测OS的独立因素。富集分析表明,高危人群免疫相关生物过程普遍富集,不同免疫状态高度浸润。我们还证实了10-PRG特征与fda批准药物的药物敏感性之间的潜在关系。综上所述,我们的研究结果为进一步探索PRG特征在LGG中的作用提供了新的认识和重要方向。
{"title":"A Novel Insight into Paraptosis-Related Classification and Signature in Lower-Grade Gliomas.","authors":"Xi-Feng Qian, Jia-Hao Zhang, Yue-Xue Mai, Xin Yin, Yu-Bin Zheng, Zi-Yuan Yu, Guo-Dong Zhu, Xu-Guang Guo","doi":"10.1155/2022/6465760","DOIUrl":"https://doi.org/10.1155/2022/6465760","url":null,"abstract":"<p><p>Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan-Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration-approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.</p>","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40702382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-11eCollection Date: 2022-01-01DOI: 10.1155/2022/4382645
Jing Zhang, Hui Li, Huling Li, Dandan Lin, Xiaoyan Wang, Kai Wang
To investigate the expression of protein disulfide isomerase A3 (PDIA3/ERP57) in cervical cancer and its clinical prognostic significance as well as its function and possible action mechanism in the progression of cervical cancer. Based on TIMER2.0 database, the human protein map (Human Protein Atlas) was used to determine the expression level of PDIA3 protein for the analysis of PDIA3 expression in 39 The Cancer Genome Atlas (TCGA) tumors. The PDIA3 expression in cervical cancer tissues in the TCGA and Genotype-Tissue Expression databases was further verified based on the GEPIA2 database to analyze the relationship between the PDIA3 expression and the pathological stage of cervical cancer patients. Immunohistochemistry was used to detect the PDIA3 expression in cervical cancer tissue microarray, including 111 cancer tissue samples and 24 adjacent cancer tissue samples, and the relationship between PDIA3 protein expression and clinical characteristics of patients with cervical cancer was analyzed. The Kaplan-Meier method and log-rank test were used for survival analysis. Based on the cBioPortal database, the Spearman's and Pearson's methods were used to analyze the correlation between PDIA3 expression and DNA methylation. The correlation between PDIA3 expression and the infiltration levels of each immune cell in cervical cancer was evaluated. The STRING was used to construct protein interaction network. Based on LinkedOmics database, the Spearman's method was used to analyze the co-expressed genes of PDIA3 in TCGA cervical cancer. The gene ontology functional enrichment analysis was performed on Top 50 differentially co-expressed genes based on DAVID database. The PDIA3 expression in cervical cancer tissues was significantly higher than that in normal tissues, which (F = 2.74, PR (>F) = 0.0436) was significantly increased with the progression of tumor stage, and PDIA3 showed strong immunoreactivity in cervical cancer tissues. In cervical cancer patients, overall survival (P = 0.014), disease-specific survival (P = 0.013), disease-free interval (P = 0.023), and progression-free interval (P = 0.001) in those with high expression of PDIA3 were significantly lower than those with low expression, suggesting that high expression of PDIA3 was associated with poor prognosis. In cervical cancer, high expression of PDIA3 was associated with DNA methylation and negatively correlated with B cell memory (r = -0.132, P = 0.021), T cell regulatory (r = -0.127, P = 0.026), monocytes (r = -0.204, P = 0), and macrophages M2 (r = -0.142, P = 0.013), whereas positively correlated with levels of NK cell activated (r = 0.162, P = 0.005) and mast cells activated (r = 0.119, P = 0.037). The genes positively correlated with PDIA3 expression included HSPA5 and PPIB, which were mainly enriched in biological processes, such as endoplasmic retic
探讨蛋白二硫异构酶A3 (PDIA3/ERP57)在宫颈癌中的表达及其临床预后意义,以及在宫颈癌进展中的作用和可能的作用机制。基于TIMER2.0数据库,利用人类蛋白图谱(human protein Atlas)测定PDIA3蛋白的表达水平,分析39例the Cancer Genome Atlas (TCGA)肿瘤中PDIA3蛋白的表达情况。以GEPIA2数据库为基础,进一步验证TCGA和Genotype-Tissue expression数据库中宫颈癌组织中PDIA3的表达,分析PDIA3表达与宫颈癌患者病理分期的关系。采用免疫组织化学方法检测111例宫颈癌组织样本及24例癌旁组织样本中PDIA3蛋白的表达,分析PDIA3蛋白表达与宫颈癌患者临床特征的关系。生存分析采用Kaplan-Meier法和log-rank检验。基于cbiopportal数据库,采用Spearman’s和Pearson’s方法分析PDIA3表达与DNA甲基化的相关性。评价宫颈癌组织中PDIA3表达与各免疫细胞浸润水平的相关性。利用STRING构建蛋白相互作用网络。基于LinkedOmics数据库,采用Spearman’s法分析TCGA宫颈癌中PDIA3共表达基因。基于DAVID数据库对Top 50个差异共表达基因进行基因本体功能富集分析。PDIA3在宫颈癌组织中的表达明显高于正常组织(F = 2.74, PR (>F) = 0.0436),随着肿瘤分期的进展,PDIA3的表达显著升高,且PDIA3在宫颈癌组织中表现出较强的免疫反应性。在宫颈癌患者中,PDIA3高表达者的总生存期(P = 0.014)、疾病特异性生存期(P = 0.013)、无病间期(P = 0.023)、无进展间期(P = 0.001)均显著低于低表达者,提示PDIA3高表达与预后不良相关。在宫颈癌中,PDIA3的高表达与DNA甲基化相关,与B细胞记忆(r = -0.132, P = 0.021)、T细胞调节(r = -0.127, P = 0.026)、单核细胞(r = -0.204, P = 0)和巨噬细胞M2 (r = -0.142, P = 0.013)呈负相关,与NK细胞活化(r = 0.162, P = 0.005)和肥大细胞活化(r = 0.119, P = 0.037)呈正相关。与PDIA3表达呈正相关的基因包括HSPA5和PPIB,这些基因主要富集于内质网蛋白折叠和内质网应激反应等生物过程中。PDIA3可作为宫颈癌预后不良的标志。PDIA3的表达水平与宫颈癌患者的生存和预后、DNA甲基化、免疫细胞浸润等密切相关。
{"title":"Expression and Prognostic Significance of PDIA3 in Cervical Cancer.","authors":"Jing Zhang, Hui Li, Huling Li, Dandan Lin, Xiaoyan Wang, Kai Wang","doi":"10.1155/2022/4382645","DOIUrl":"https://doi.org/10.1155/2022/4382645","url":null,"abstract":"<p><p>To investigate the expression of protein disulfide isomerase A3 (PDIA3/ERP57) in cervical cancer and its clinical prognostic significance as well as its function and possible action mechanism in the progression of cervical cancer. Based on TIMER2.0 database, the human protein map (Human Protein Atlas) was used to determine the expression level of PDIA3 protein for the analysis of PDIA3 expression in 39 The Cancer Genome Atlas (TCGA) tumors. The PDIA3 expression in cervical cancer tissues in the TCGA and Genotype-Tissue Expression databases was further verified based on the GEPIA2 database to analyze the relationship between the PDIA3 expression and the pathological stage of cervical cancer patients. Immunohistochemistry was used to detect the PDIA3 expression in cervical cancer tissue microarray, including 111 cancer tissue samples and 24 adjacent cancer tissue samples, and the relationship between PDIA3 protein expression and clinical characteristics of patients with cervical cancer was analyzed. The Kaplan-Meier method and log-rank test were used for survival analysis. Based on the cBioPortal database, the Spearman's and Pearson's methods were used to analyze the correlation between PDIA3 expression and DNA methylation. The correlation between PDIA3 expression and the infiltration levels of each immune cell in cervical cancer was evaluated. The STRING was used to construct protein interaction network. Based on LinkedOmics database, the Spearman's method was used to analyze the co-expressed genes of PDIA3 in TCGA cervical cancer. The gene ontology functional enrichment analysis was performed on Top 50 differentially co-expressed genes based on DAVID database. The PDIA3 expression in cervical cancer tissues was significantly higher than that in normal tissues, which (<i>F</i> = 2.74, PR (><i>F</i>) = 0.0436) was significantly increased with the progression of tumor stage, and PDIA3 showed strong immunoreactivity in cervical cancer tissues. In cervical cancer patients, overall survival (<i>P</i> = 0.014), disease-specific survival (<i>P</i> = 0.013), disease-free interval (<i>P</i> = 0.023), and progression-free interval (<i>P</i> = 0.001) in those with high expression of PDIA3 were significantly lower than those with low expression, suggesting that high expression of PDIA3 was associated with poor prognosis. In cervical cancer, high expression of PDIA3 was associated with DNA methylation and negatively correlated with B cell memory (<i>r</i> = -0.132, <i>P</i> = 0.021), T cell regulatory (<i>r</i> = -0.127, <i>P</i> = 0.026), monocytes (<i>r</i> = -0.204, <i>P</i> = 0), and macrophages M2 (<i>r</i> = -0.142, <i>P</i> = 0.013), whereas positively correlated with levels of NK cell activated (<i>r</i> = 0.162, <i>P</i> = 0.005) and mast cells activated (<i>r</i> = 0.119, <i>P</i> = 0.037). The genes positively correlated with PDIA3 expression included HSPA5 and PPIB, which were mainly enriched in biological processes, such as endoplasmic retic","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40503082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-20eCollection Date: 2022-01-01DOI: 10.1155/2022/8775330
Si-Tong Lin, Zi-Qian Liang, Xiao-Yu Chen, Xin-Qing Ye, Yu-Yan Pang, Jia-Yuan Luo, Jun-Hong Chen, Yi-Wu Dang, Gang Chen
Aim: The aim of this study is to demonstrate the expression and clinicopathological significance of complement C1q B chain (C1QB) in cervical cancer.
Methods: In total, 120 cervical cancer tissues, as well as 20 samples each of high-grade squamous intraepithelial lesions (HSILs), low-grade squamous intraepithelial lesions (LSILs), and benign cervical tissue, were collected to evaluate the expression of C1QB protein via immunohistochemical staining. We conducted an integrated analysis of C1QB mRNA expression in cervical cancer using public microarrays and RNA-seq data sets by calculating standard mean differences (SMDs). Simultaneously, we explored the relations of C1QB with clinicopathological parameters and the expression of P16, Ki-67, and P53.
Results: The expression of C1QB protein was higher in cervical cancer samples than that in benign cervical tissue, LSIL, and HSIL samples (p < 0.05). A combined SMD of 0.65 (95% CI: [0.52, 0.79], p < 0.001) revealed upregulation of C1QB mRNA in cervical cancer. C1QB expression may also be related to the depth of infiltration, lymphovascular invasion, and perineural invasion in cervical cancer (p < 0.05). We also found that C1QB protein expression was positively correlated with P16 and Ki-67 expression in cervical cancer (p < 0.05). The gene set enrichment analysis showed that C1QB may participate in apoptosis and autophagy. A relationship was predicted between C1QB expression and drug sensitivity to cisplatin, paclitaxel, and docetaxel.
Conclusion: We confirmed the overexpression of C1QB in cervical cancer at both mRNA and protein levels for the first time. C1QB may serve as an oncogene in the tumorigenesis of cervical cancer, but this possibility requires further study.
{"title":"Detection of Complement C1q B Chain Overexpression and Its Latent Molecular Mechanisms in Cervical Cancer Tissues Using Multiple Methods.","authors":"Si-Tong Lin, Zi-Qian Liang, Xiao-Yu Chen, Xin-Qing Ye, Yu-Yan Pang, Jia-Yuan Luo, Jun-Hong Chen, Yi-Wu Dang, Gang Chen","doi":"10.1155/2022/8775330","DOIUrl":"https://doi.org/10.1155/2022/8775330","url":null,"abstract":"<p><strong>Aim: </strong>The aim of this study is to demonstrate the expression and clinicopathological significance of complement C1q B chain (<i>C1QB</i>) in cervical cancer.</p><p><strong>Methods: </strong>In total, 120 cervical cancer tissues, as well as 20 samples each of high-grade squamous intraepithelial lesions (HSILs), low-grade squamous intraepithelial lesions (LSILs), and benign cervical tissue, were collected to evaluate the expression of <i>C1QB</i> protein via immunohistochemical staining. We conducted an integrated analysis of <i>C1QB</i> mRNA expression in cervical cancer using public microarrays and RNA-seq data sets by calculating standard mean differences (SMDs). Simultaneously, we explored the relations of <i>C1QB</i> with clinicopathological parameters and the expression of P16, Ki-67, and P53.</p><p><strong>Results: </strong>The expression of <i>C1QB</i> protein was higher in cervical cancer samples than that in benign cervical tissue, LSIL, and HSIL samples (<i>p</i> < 0.05). A combined SMD of 0.65 (95% CI: [0.52, 0.79], <i>p</i> < 0.001) revealed upregulation of <i>C1QB</i> mRNA in cervical cancer. <i>C1QB</i> expression may also be related to the depth of infiltration, lymphovascular invasion, and perineural invasion in cervical cancer (<i>p</i> < 0.05). We also found that <i>C1QB</i> protein expression was positively correlated with P16 and Ki-67 expression in cervical cancer (<i>p</i> < 0.05). The gene set enrichment analysis showed that <i>C1QB</i> may participate in apoptosis and autophagy. A relationship was predicted between <i>C1QB</i> expression and drug sensitivity to cisplatin, paclitaxel, and docetaxel.</p><p><strong>Conclusion: </strong>We confirmed the overexpression of <i>C1QB</i> in cervical cancer at both mRNA and protein levels for the first time. <i>C1QB</i> may serve as an oncogene in the tumorigenesis of cervical cancer, but this possibility requires further study.</p>","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40439088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ALDH1A3 and Linc00284 involve in colorectal cancer (CRC) development; however, the regulatory mechanism is still unclear. In this study, we collected clinicopathological characteristics and tissue samples from 73 CRC patients to analyze the expression of ALDH1A3, Linc00284, TGFβ signaling and miR-361-5p using qPCR, Western blotting, and ELISA. Multiple CRC cell lines were evaluated in this study, and the highest level of ALDH1A3 was observed in SW480 cells. To investigate the regulatory mechanism, RIP and luciferase assays were used to validate the interaction between Linc00284, miR-361-5p, and TGFβ. Proliferation, viability, migration, and invasion assays were performed to profile the effects of the ALDH1A3-Linc00284 axis in CRC cell functions, which was upregulated in CRC tissues. Knockdown ALDH1A3 or Linc00284 significantly reduced TGFβ expression and suppressed the EMT process, while overexpression had opposite effects. miR-361-5p targeted TGFβ directly, which negatively correlated with ALDH1A3-Linc00284 expression and CRC progression. Mechanistically, upregulation of ALDH1A3-Linc00284 promotes colorectal cancer invasion and migration by regulating miR-361-5p/TGFβ signaling pathway. Dysregulation of the ALDH1A3-Linc00284-miR-361-5p-TGFβ axis causes CRC invasion, which might provide a new insight into the treatment of CRC.
{"title":"ALDH1A3-Linc00284 Axis Mediates the Invasion of Colorectal Cancer by Targeting TGF<i>β</i> Signaling via Sponging miR-361-5p.","authors":"Chunlin Ke, Minmin Shen, Peirong Wang, Zhihua Chen, Suyong Lin, Feng Dong","doi":"10.1155/2022/6561047","DOIUrl":"https://doi.org/10.1155/2022/6561047","url":null,"abstract":"<p><p>ALDH1A3 and Linc00284 involve in colorectal cancer (CRC) development; however, the regulatory mechanism is still unclear. In this study, we collected clinicopathological characteristics and tissue samples from 73 CRC patients to analyze the expression of ALDH1A3, Linc00284, TGF<i>β</i> signaling and miR-361-5p using qPCR, Western blotting, and ELISA. Multiple CRC cell lines were evaluated in this study, and the highest level of ALDH1A3 was observed in SW480 cells. To investigate the regulatory mechanism, RIP and luciferase assays were used to validate the interaction between Linc00284, miR-361-5p, and TGF<i>β</i>. Proliferation, viability, migration, and invasion assays were performed to profile the effects of the ALDH1A3-Linc00284 axis in CRC cell functions, which was upregulated in CRC tissues. Knockdown ALDH1A3 or Linc00284 significantly reduced TGF<i>β</i> expression and suppressed the EMT process, while overexpression had opposite effects. miR-361-5p targeted TGF<i>β</i> directly, which negatively correlated with ALDH1A3-Linc00284 expression and CRC progression. Mechanistically, upregulation of ALDH1A3-Linc00284 promotes colorectal cancer invasion and migration by regulating miR-361-5p/TGF<i>β</i> signaling pathway. Dysregulation of the ALDH1A3-Linc00284-miR-361-5p-TGF<i>β</i> axis causes CRC invasion, which might provide a new insight into the treatment of CRC.</p>","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40664292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-13eCollection Date: 2022-01-01DOI: 10.1155/2022/5265686
Woori Jang, Joonhong Park, Hyojin Chae, Myungshin Kim
Assessing the impact of variants of unknown significance on splicing has become a critical issue and a bottleneck, especially with the widespread implementation of whole-genome or exome sequencing. Although multiple in silico tools are available, the interpretation and application of these tools are difficult and practical guidelines are still lacking. A streamlined decision-making process can facilitate the downstream RNA analysis in a more efficient manner. Therefore, we evaluated the performance of 8 in silico tools (Splice Site Finder, MaxEntScan, Splice-site prediction by neural network, GeneSplicer, Human Splicing Finder, SpliceAI, Splicing Predictions in Consensus Elements, and SpliceRover) using 114 NF1 spliceogenic variants, experimentally validated at the mRNA level. The change in the predicted score incurred by the variant of the nearest wild-type splice site was analyzed, and for type II, III, and IV splice variants, the change in the prediction score of de novo or cryptic splice site was also analyzed. SpliceAI and SpliceRover, tools based on deep learning, outperformed all other tools, with AUCs of 0.972 and 0.924, respectively. For de novo and cryptic splice sites, SpliceAI outperformed all other tools and showed a sensitivity of 95.7% at an optimal cut-off of 0.02 score change. Our results show that deep learning algorithms, especially those of SpliceAI, are validated at a significantly higher rate than other in silico tools for clinically relevant NF1 variants. This suggests that deep learning algorithms outperform traditional probabilistic approaches and classical machine learning tools in predicting the de novo and cryptic splice sites.
评估未知意义变异对剪接的影响已成为一个关键问题和瓶颈,特别是随着全基因组或外显子组测序的广泛实施。虽然有多种计算机工具可用,但这些工具的解释和应用是困难的,并且仍然缺乏实用的指导方针。简化的决策过程可以更有效地促进下游RNA分析。因此,我们使用114种NF1剪接基因变异,在mRNA水平上进行了实验验证,评估了8种计算机工具(Splice Site Finder、MaxEntScan、神经网络剪接位点预测、GeneSplicer、Human Splicing Finder、SpliceAI、SpliceRover)的性能。分析了最近野生型剪接位点变异引起的预测分数变化,并分析了II型、III型和IV型剪接变异引起的新剪接位点或隐剪接位点预测分数的变化。基于深度学习的工具SpliceAI和SpliceRover的auc分别为0.972和0.924,优于所有其他工具。对于新生剪接位点和隐剪接位点,SpliceAI优于所有其他工具,在0.02分变化的最佳截止值下显示出95.7%的灵敏度。我们的研究结果表明,深度学习算法,特别是SpliceAI的算法,在临床相关NF1变异方面的验证率明显高于其他计算机工具。这表明深度学习算法在预测新剪接位点和隐剪接位点方面优于传统的概率方法和经典的机器学习工具。
{"title":"Comparison of <i>In Silico</i> Tools for Splice-Altering Variant Prediction Using Established Spliceogenic Variants: An End-User's Point of View.","authors":"Woori Jang, Joonhong Park, Hyojin Chae, Myungshin Kim","doi":"10.1155/2022/5265686","DOIUrl":"https://doi.org/10.1155/2022/5265686","url":null,"abstract":"<p><p>Assessing the impact of variants of unknown significance on splicing has become a critical issue and a bottleneck, especially with the widespread implementation of whole-genome or exome sequencing. Although multiple <i>in silico</i> tools are available, the interpretation and application of these tools are difficult and practical guidelines are still lacking. A streamlined decision-making process can facilitate the downstream RNA analysis in a more efficient manner. Therefore, we evaluated the performance of 8 <i>in silico</i> tools (Splice Site Finder, MaxEntScan, Splice-site prediction by neural network, GeneSplicer, Human Splicing Finder, SpliceAI, Splicing Predictions in Consensus Elements, and SpliceRover) using 114 <i>NF1</i> spliceogenic variants, experimentally validated at the mRNA level. The change in the predicted score incurred by the variant of the nearest wild-type splice site was analyzed, and for type II, III, and IV splice variants, the change in the prediction score of <i>de novo</i> or cryptic splice site was also analyzed. SpliceAI and SpliceRover, tools based on deep learning, outperformed all other tools, with AUCs of 0.972 and 0.924, respectively. For <i>de novo</i> and cryptic splice sites, SpliceAI outperformed all other tools and showed a sensitivity of 95.7% at an optimal cut-off of 0.02 score change. Our results show that deep learning algorithms, especially those of SpliceAI, are validated at a significantly higher rate than other <i>in silico</i> tools for clinically relevant <i>NF1</i> variants. This suggests that deep learning algorithms outperform traditional probabilistic approaches and classical machine learning tools in predicting the <i>de novo</i> and cryptic splice sites.</p>","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40652060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-10eCollection Date: 2022-01-01DOI: 10.1155/2022/9083822
Lixue Liu, Ru Bai, Debang Li, Bai Dai, Ya Tuo
Long non-coding RNA (LncRNA) emerges as a regulator in various diseases, including endometriosis (EM). This study aims to uncover the role of long non-coding RNA BRAF-activated non-protein coding RNA (lncRNA BANCR)-mediated competing endogenous RNA mechanism in endometrial stromal cell (ESC) proliferation and invasion in EM by regulating miR-15a-5p/TRIM59. ESCs were isolated from eutopic and ectopic endometrial tissues, followed by the determination of Cytokeratin 19 and Vimentin expressions in cells. Then, expressions of lncRNA BANCR, microRNA (miR)-15a-5p, and tripartite motif-containing 59 (TRIM59) in tissues and cells were determined by real-time quantitative polymerase chain reaction or Western blot assay, and cell proliferation and invasion were evaluated by cell counting kit-8 and transwell assays. After that, the subcellular localization of lncRNA BANCR and binding of miR-15a-5p to lncRNA BANCR or TRIM59 were analyzed. LncRNA BANCR was upregulated in ectopic endometrial tissues and ectopic ESCs (Ect-ESCs). Silencing lncRNA BANCR suppressed Ect-ESC proliferation and invasion. LncRNA BANCR inhibited miR-15a-5p to promote TRIM59 expression. miR-15a-5p downregulation or TRIM59 overexpression both reversed the effects of silencing lncRNA BANCR on Ect-ESC proliferation and invasion. In summary, our findings suggested that lncRNA BANCR facilitated Ect-ESC proliferation and invasion by inhibiting miR-15a-5p and promoting TRIM59.
{"title":"<i>LncRNA BANCR</i> Promotes Endometrial Stromal Cell Proliferation and Invasion in Endometriosis via the <i>miR-15a-5p</i>/TRIM59 Axis.","authors":"Lixue Liu, Ru Bai, Debang Li, Bai Dai, Ya Tuo","doi":"10.1155/2022/9083822","DOIUrl":"https://doi.org/10.1155/2022/9083822","url":null,"abstract":"<p><p>Long non-coding RNA (LncRNA) emerges as a regulator in various diseases, including endometriosis (EM). This study aims to uncover the role of <i>long non-coding RNA BRAF-activated non-protein coding RNA</i> (<i>lncRNA BANCR</i>)-mediated competing endogenous RNA mechanism in endometrial stromal cell (ESC) proliferation and invasion in EM by regulating <i>miR-15a-5p</i>/TRIM59. ESCs were isolated from eutopic and ectopic endometrial tissues, followed by the determination of Cytokeratin 19 and Vimentin expressions in cells. Then, expressions of <i>lncRNA BANCR</i>, <i>microRNA (miR)-15a-5p</i>, and tripartite motif-containing 59 (TRIM59) in tissues and cells were determined by real-time quantitative polymerase chain reaction or Western blot assay, and cell proliferation and invasion were evaluated by cell counting kit-8 and transwell assays. After that, the subcellular localization of <i>lncRNA BANCR</i> and binding of <i>miR-15a-5p</i> to <i>lncRNA BANCR</i> or TRIM59 were analyzed. <i>LncRNA BANCR</i> was upregulated in ectopic endometrial tissues and ectopic ESCs (Ect-ESCs). Silencing <i>lncRNA BANCR</i> suppressed Ect-ESC proliferation and invasion. <i>LncRNA BANCR</i> inhibited <i>miR-15a-5p</i> to promote TRIM59 expression. <i>miR-15a-5p</i> downregulation or TRIM59 overexpression both reversed the effects of silencing <i>lncRNA BANCR</i> on Ect-ESC proliferation and invasion. In summary, our findings suggested that <i>lncRNA BANCR</i> facilitated Ect-ESC proliferation and invasion by inhibiting <i>miR-15a-5p</i> and promoting TRIM59.</p>","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40646889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-10eCollection Date: 2022-01-01DOI: 10.1155/2022/9264555
Shengqiang Jiang, Jie Wu, Yan Geng, Yuting Zhang, Yupeng Wang, Jinrong Wu, Chunqu Lu, Guoxuan Luo, Jie Zan, Yong Zhang
Ischemic stroke (IS) is one of the leading causes of disability and mortality worldwide. This study aims to find the crucial exosomal miRNAs associated with IS by using bioinformatics methods, reveal potential biomarkers for IS, and investigate the association between the identified biomarker and immune cell pattern in the peripheral blood of IS patients. In this study, 3 up-regulated miRNAs (hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p) miRNAs in the serum exosomes between IS patients and healthy controls from GEO database (GSE199942) and 25 down-regulated genes of peripheral blood mononuclear cells of IS patients from GSE22255 were obtained with the help of the R software. GO annotation and KEGG pathway enrichment analysis showed that the 25 down-regulated genes were associated with coenzyme metabolic process and were mainly enriched in the N-glycan biosynthesis pathway. Furthermore, we performed the LASSO algorithm to narrow down the above 25 intersected genes, and identified 8 key genes which had a good diagnostic value in discriminating IS patients from the healthy controls analyzed with ROC curve. CIBERSORT algorithm indicated that the abundance of M0 macrophages and resting mast cells was significantly lower than that of the control group. The spearman correlation analysis showed that STT3A was negatively correlated with the proportion of follicular helper T cells, activated NK cells and resting dendritic cells. Finally, GSE117064 showed that has-miR-16-5p was more advantageous for diagnosing stroke. In conclusion, hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p are identified as specific related exosomal miRNAs for IS patients. These genes may provide new targets for the early identification of IS.
{"title":"Identification of Differentially Expressed microRNAs Associated with Ischemic Stroke by Integrated Bioinformatics Approaches.","authors":"Shengqiang Jiang, Jie Wu, Yan Geng, Yuting Zhang, Yupeng Wang, Jinrong Wu, Chunqu Lu, Guoxuan Luo, Jie Zan, Yong Zhang","doi":"10.1155/2022/9264555","DOIUrl":"https://doi.org/10.1155/2022/9264555","url":null,"abstract":"<p><p>Ischemic stroke (IS) is one of the leading causes of disability and mortality worldwide. This study aims to find the crucial exosomal miRNAs associated with IS by using bioinformatics methods, reveal potential biomarkers for IS, and investigate the association between the identified biomarker and immune cell pattern in the peripheral blood of IS patients. In this study, 3 up-regulated miRNAs (hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p) miRNAs in the serum exosomes between IS patients and healthy controls from GEO database (GSE199942) and 25 down-regulated genes of peripheral blood mononuclear cells of IS patients from GSE22255 were obtained with the help of the R software. GO annotation and KEGG pathway enrichment analysis showed that the 25 down-regulated genes were associated with coenzyme metabolic process and were mainly enriched in the N-glycan biosynthesis pathway. Furthermore, we performed the LASSO algorithm to narrow down the above 25 intersected genes, and identified 8 key genes which had a good diagnostic value in discriminating IS patients from the healthy controls analyzed with ROC curve. CIBERSORT algorithm indicated that the abundance of M0 macrophages and resting mast cells was significantly lower than that of the control group. The spearman correlation analysis showed that STT3A was negatively correlated with the proportion of follicular helper T cells, activated NK cells and resting dendritic cells. Finally, GSE117064 showed that has-miR-16-5p was more advantageous for diagnosing stroke. In conclusion, hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p are identified as specific related exosomal miRNAs for IS patients. These genes may provide new targets for the early identification of IS.</p>","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40646888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coxsackievirus B5 (CVB5) is the causative agent of hand, foot, and mouth disease (HFMD) that can cause neurological complications and fatalities. Circular RNA (circRNA) has been shown to play an important role in regulating pathogenic processes. However, the functions of circRNA in response to CVB5 infection remain unclear. In our research, RNA-seq was employed to analyze the expression profiles of circRNAs in SH-SY5Y cells with or without CVB5 infection. Out of 5,665 circRNAs identified to be expressed in SH-SY5Y cells, 163 circRNAs were found to be differentially expressed significantly. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the differentially expressed circRNAs were mainly involved in ubiquitin-mediated proteolysis and signaling pathways during CVB5 infection. Additionally, RT-qPCR was used to validate the RNA-seq data, and a circRNA-miRNA-mRNA interaction network was constructed based on two circRNAs, such as hsa_circ_0008378 and novel_circ_0014617, which were associated with the regulation of innate immune response in host cells. Additionally, we confirmed the two circRANs up-regulated the key factors in the IFN-I signaling pathway, hampering viral replication. Our data provide a new perspective that facilitates further understanding of the virus-host mechanism.
{"title":"Expression Profiles of Differentially Expressed Circular RNAs and circRNA-miRNA-mRNA Regulatory Networks in SH-SY5Y Cells Infected with Coxsackievirus B5.","authors":"Jing Li, Heng Yang, Huaran Shi, Jihong Zhang, Wei Chen","doi":"10.1155/2022/9298149","DOIUrl":"10.1155/2022/9298149","url":null,"abstract":"<p><p>Coxsackievirus B5 (CVB5) is the causative agent of hand, foot, and mouth disease (HFMD) that can cause neurological complications and fatalities. Circular RNA (circRNA) has been shown to play an important role in regulating pathogenic processes. However, the functions of circRNA in response to CVB5 infection remain unclear. In our research, RNA-seq was employed to analyze the expression profiles of circRNAs in SH-SY5Y cells with or without CVB5 infection. Out of 5,665 circRNAs identified to be expressed in SH-SY5Y cells, 163 circRNAs were found to be differentially expressed significantly. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the differentially expressed circRNAs were mainly involved in ubiquitin-mediated proteolysis and signaling pathways during CVB5 infection. Additionally, RT-qPCR was used to validate the RNA-seq data, and a circRNA-miRNA-mRNA interaction network was constructed based on two circRNAs, such as hsa_circ_0008378 and novel_circ_0014617, which were associated with the regulation of innate immune response in host cells. Additionally, we confirmed the two circRANs up-regulated the key factors in the IFN-I signaling pathway, hampering viral replication. Our data provide a new perspective that facilitates further understanding of the virus-host mechanism.</p>","PeriodicalId":13988,"journal":{"name":"International Journal of Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40563360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}