Pub Date : 2024-09-24DOI: 10.2174/0122115366320538240912080053
Hamid Jamialahmadi, Alireza Asadnia, Ghazaleh Khalili-Tanha, Reza Mohit, Hanieh Azari, Majid Khazaei, Mina Maftooh, Mohammadreza Nassiri, Seyed Mahdi Hassanian, Majid Ghayour-Mobarhan, Gordon A Ferns, Elham Nazari, Amir Avan
Introduction: The differential expression of miRNAs, a key regulator in many cell signaling pathways, has been studied in various malignancies and may have an important role in cancer progression, including colorectal cancer (CRC).
Method: The present study used machine learning and gene interaction study tools to explore the prognostic and diagnostic value of miRNAs in CRC. Integrative analysis of 353 CRC samples and normal tissue data was obtained from the TCGA database and further analyzed by R packages to define the deferentially expressed miRNAs (DEMs). Furthermore, machine learning and Kaplan Meier survival analysis helped better specify the significant prognostic value of miRNAs. A combination of online databases was then used to evaluate the interactions between target genes, their molecular pathways, and the correlation between the DEMs.
Result: The results indicated that miR-19b and miR-20a have a significant prognostic role and are associated with CRC progression. The ROC curve analysis discovered that miR-20a alone and combined with other miRNAs, including hsa-mir-21 and hsa-mir-542, are diagnostic biomarkers in CRC. In addition, 12 genes, including NTRK2, CDC42, EGFR, AGO2, PRKCA, HSP90AA1, TLR4, IGF1, ESR1, SMAD2, SMAD4, and NEDD4L, were found to be the highest score targets for these miRNAs. Pathway analysis identified the two correlated tyrosine kinase and MAPK signaling pathways with the key interaction genes, i.e., EGFR, CDC42, and HSP90AA1.
Conclusion: To better define the role of these miRNAs, the ceRNA network, including lncRNAs, was also prepared. In conclusion, the combination of R data analysis and machine learning provides a robust approach to resolving complicated interactions between miRNAs and their targets.
{"title":"Identification of miR-20a as a Diagnostic and Prognostic Biomarker in Colorectal Cancer: MicroRNA Sequencing and Machine Learning Analysis.","authors":"Hamid Jamialahmadi, Alireza Asadnia, Ghazaleh Khalili-Tanha, Reza Mohit, Hanieh Azari, Majid Khazaei, Mina Maftooh, Mohammadreza Nassiri, Seyed Mahdi Hassanian, Majid Ghayour-Mobarhan, Gordon A Ferns, Elham Nazari, Amir Avan","doi":"10.2174/0122115366320538240912080053","DOIUrl":"https://doi.org/10.2174/0122115366320538240912080053","url":null,"abstract":"<p><strong>Introduction: </strong>The differential expression of miRNAs, a key regulator in many cell signaling pathways, has been studied in various malignancies and may have an important role in cancer progression, including colorectal cancer (CRC).</p><p><strong>Method: </strong>The present study used machine learning and gene interaction study tools to explore the prognostic and diagnostic value of miRNAs in CRC. Integrative analysis of 353 CRC samples and normal tissue data was obtained from the TCGA database and further analyzed by R packages to define the deferentially expressed miRNAs (DEMs). Furthermore, machine learning and Kaplan Meier survival analysis helped better specify the significant prognostic value of miRNAs. A combination of online databases was then used to evaluate the interactions between target genes, their molecular pathways, and the correlation between the DEMs.</p><p><strong>Result: </strong>The results indicated that miR-19b and miR-20a have a significant prognostic role and are associated with CRC progression. The ROC curve analysis discovered that miR-20a alone and combined with other miRNAs, including hsa-mir-21 and hsa-mir-542, are diagnostic biomarkers in CRC. In addition, 12 genes, including NTRK2, CDC42, EGFR, AGO2, PRKCA, HSP90AA1, TLR4, IGF1, ESR1, SMAD2, SMAD4, and NEDD4L, were found to be the highest score targets for these miRNAs. Pathway analysis identified the two correlated tyrosine kinase and MAPK signaling pathways with the key interaction genes, i.e., EGFR, CDC42, and HSP90AA1.</p><p><strong>Conclusion: </strong>To better define the role of these miRNAs, the ceRNA network, including lncRNAs, was also prepared. In conclusion, the combination of R data analysis and machine learning provides a robust approach to resolving complicated interactions between miRNAs and their targets.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.2174/0122115366304114240904051429
Amir Mohammad Salehi, Fatemeh Torogi, Farid Azizi Jalilian, Razieh Amini
Introduction: Curcumin is known as a bioactive component that is found in the rhizomes of Curcuma longa. Curcumin is well known for its chemo-preventive and anticancer properties. However, its anticancer mechanism in colorectal cancer treatment is unclear, and some studies have shown that many microRNAs (miRs) could be potential targets for curcumin in colorectal cancer (CRC) treatment, so there is a need for their integration and clarification.
Methods: We systematically searched international databases, including PubMed, Scopus, and Web of Science, until July 2021 by using some relevant keywords.
Results: The search resulted in 87 papers, among which there were 18 related articles. Curcumin was found to cause the upregulation of miR-497, miR-200c, miR-200b, miR-409-3p, miR-34, miR-126, miR-145, miR-206, miR-491, miR-141, miR-429, miR-101, and miR-15a and the downregulation of miR-21, miR-155, miR-221, miR-222, miR-17-5p, miR-130a, miR-27, and miR-20a.
Conclusion: The present review study suggests that curcumin may be useful as a novel therapeutic agent for CRC by altering the expression level of miRs.
{"title":"The Potential Role of Curcumin as a Regulator of microRNA in Colorectal Cancer: A Systematic Review.","authors":"Amir Mohammad Salehi, Fatemeh Torogi, Farid Azizi Jalilian, Razieh Amini","doi":"10.2174/0122115366304114240904051429","DOIUrl":"https://doi.org/10.2174/0122115366304114240904051429","url":null,"abstract":"<p><strong>Introduction: </strong>Curcumin is known as a bioactive component that is found in the rhizomes of Curcuma longa. Curcumin is well known for its chemo-preventive and anticancer properties. However, its anticancer mechanism in colorectal cancer treatment is unclear, and some studies have shown that many microRNAs (miRs) could be potential targets for curcumin in colorectal cancer (CRC) treatment, so there is a need for their integration and clarification.</p><p><strong>Methods: </strong>We systematically searched international databases, including PubMed, Scopus, and Web of Science, until July 2021 by using some relevant keywords.</p><p><strong>Results: </strong>The search resulted in 87 papers, among which there were 18 related articles. Curcumin was found to cause the upregulation of miR-497, miR-200c, miR-200b, miR-409-3p, miR-34, miR-126, miR-145, miR-206, miR-491, miR-141, miR-429, miR-101, and miR-15a and the downregulation of miR-21, miR-155, miR-221, miR-222, miR-17-5p, miR-130a, miR-27, and miR-20a.</p><p><strong>Conclusion: </strong>The present review study suggests that curcumin may be useful as a novel therapeutic agent for CRC by altering the expression level of miRs.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.2174/0122115366299210240823062457
Wei Zhou, Jia Hu, Jun Nie
Background: Myasthenia gravis is an autoimmune disease, and 30% of patients with thymoma often have myasthenia gravis. Patients with thymoma-associated MG (TAMG) have many different clinical presentations compared to non-MG thymoma (NMG), yet their gene expression differences remain unclear.
Objective: In this study, we analyzed the Differentially Expressed Genes (DEGs) and analyzed their regulatory microRNAs (miRNAs) in TAMG, which will further clarify the possible pathogenesis of TAMG.
Methods: DEGs were calculated using the RNA-sequencing data of TAMG and NMG downloaded from The Cancer Genome Atlas (TCGA) database. R software was then used to analyze the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs, while STRING was applied to build the protein-protein interaction (PPI) network and Cytoscape to identify and visualize the hub genes. Immune infiltration significances of hub genes were also explored by using the TIMER database and TCGA database. Upstream microRNAs (miRNAs) of the hub genes were predicted by online software.
Results: We comparatively analyzed the gene expression differences between TAMG and NMG groups. A total of 977 DEGs were identified between the two groups (|log fold change (FC)| >2, adjusted P value <0.050), with 555 down-regulated genes and 422 up-regulated genes. Five top hub genes (CTNNB1, EGFR, SOX2, ERBB2, and EGF) were recognized in the PPI network. Analysis based on the TIMER and TCGA databases suggested that 5 hub genes were correlated with multiple immune cell infiltrations and immune checkpoint-related markers, such as PDCD1, CTLA-4, and CD274, in TAMG patients. Lastly, 5 miRNAs were identified to have the potential function of regulating the hub gene expression.
Conclusion: Our study identified 5 hub genes (CTNNB1, EGFR, SOX2, ERBB2, and EGF) and their 5 regulatory miRNAs in TAMG, and the hub genes were correlated with multiple immune cell infiltrations and immune checkpoint-related markers. Our findings could help partially clarify the pathophysiology of TAMG, which could be new potential targets for subsequent clinical immunotherapy.
背景:重症肌无力是一种自身免疫性疾病,30%的胸腺瘤患者通常伴有重症肌无力。胸腺瘤相关肌萎缩症(TAMG)患者的临床表现与非肌萎缩症胸腺瘤(NMG)相比有许多不同之处,但其基因表达差异仍不清楚:本研究分析了TAMG的差异表达基因(DEGs),并分析了其调控微RNAs(miRNAs),这将进一步阐明TAMG可能的发病机制:利用从癌症基因组图谱(TCGA)数据库下载的TAMG和NMG的RNA测序数据计算DEGs。然后用R软件分析DEGs的基因本体(GO)和京都基因组百科全书(KEGG)通路,用STRING构建蛋白-蛋白相互作用(PPI)网络,用Cytoscape识别和可视化枢纽基因。此外,还利用TIMER数据库和TCGA数据库探讨了中心基因的免疫浸润意义。通过在线软件预测了枢纽基因的上游微RNA(miRNA):我们比较分析了TAMG组和NMG组的基因表达差异。结果:我们比较分析了 TAMG 组和 NMG 组的基因表达差异,发现两组间共有 977 个 DEGs(log fold change (FC)| >2, adjusted P value 结论):我们的研究发现了TAMG中的5个中枢基因(CTNNB1、表皮生长因子受体、SOX2、ERBB2和EGF)及其5个调控miRNA,这些中枢基因与多种免疫细胞浸润和免疫检查点相关标志物相关。我们的发现有助于部分阐明TAMG的病理生理学,这可能成为后续临床免疫疗法的潜在新靶点。
{"title":"Identification of Hub Genes and Analysis of their Regulatory miRNAs in Patients with Thymoma Associated Myasthenia Gravis Based on TCGA Database.","authors":"Wei Zhou, Jia Hu, Jun Nie","doi":"10.2174/0122115366299210240823062457","DOIUrl":"https://doi.org/10.2174/0122115366299210240823062457","url":null,"abstract":"<p><strong>Background: </strong>Myasthenia gravis is an autoimmune disease, and 30% of patients with thymoma often have myasthenia gravis. Patients with thymoma-associated MG (TAMG) have many different clinical presentations compared to non-MG thymoma (NMG), yet their gene expression differences remain unclear.</p><p><strong>Objective: </strong>In this study, we analyzed the Differentially Expressed Genes (DEGs) and analyzed their regulatory microRNAs (miRNAs) in TAMG, which will further clarify the possible pathogenesis of TAMG.</p><p><strong>Methods: </strong>DEGs were calculated using the RNA-sequencing data of TAMG and NMG downloaded from The Cancer Genome Atlas (TCGA) database. R software was then used to analyze the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs, while STRING was applied to build the protein-protein interaction (PPI) network and Cytoscape to identify and visualize the hub genes. Immune infiltration significances of hub genes were also explored by using the TIMER database and TCGA database. Upstream microRNAs (miRNAs) of the hub genes were predicted by online software.</p><p><strong>Results: </strong>We comparatively analyzed the gene expression differences between TAMG and NMG groups. A total of 977 DEGs were identified between the two groups (|log fold change (FC)| >2, adjusted P value <0.050), with 555 down-regulated genes and 422 up-regulated genes. Five top hub genes (CTNNB1, EGFR, SOX2, ERBB2, and EGF) were recognized in the PPI network. Analysis based on the TIMER and TCGA databases suggested that 5 hub genes were correlated with multiple immune cell infiltrations and immune checkpoint-related markers, such as PDCD1, CTLA-4, and CD274, in TAMG patients. Lastly, 5 miRNAs were identified to have the potential function of regulating the hub gene expression.</p><p><strong>Conclusion: </strong>Our study identified 5 hub genes (CTNNB1, EGFR, SOX2, ERBB2, and EGF) and their 5 regulatory miRNAs in TAMG, and the hub genes were correlated with multiple immune cell infiltrations and immune checkpoint-related markers. Our findings could help partially clarify the pathophysiology of TAMG, which could be new potential targets for subsequent clinical immunotherapy.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: MicroRNAs (miRNAs), a distinct category of non-coding RNAs, exert multifaceted regulatory functions in a variety of organisms, including humans, animals, and plants. The inventory of identified miRNAs stands at approximately 60,000 among all species, and 1,926 in Homo sapiens manifest miRNA expression.
Method: Their theranostic role has been explored by researchers over the last few decades, positioning them as prominent therapeutic targets as our understanding of RNA targeting advances. However, the limited availability of experimentally determined miRNA structures has constrained drug discovery efforts relying on virtual screening or computational methods, including machine learning and artificial intelligence.
Results: To address this lacuna, miRVim has been developed, providing a repository of human miRNA structures derived from both two-dimensional (MXFold2, CentroidFold, and RNAFold) and three-dimensional (RNAComposer and 3dRNA) structure prediction algorithms, in addition to experimentally available structures from the RCSB PDB repository. miRVim contains 13,971 predicted secondary structures and 17,045 predicted three-dimensional structures, filling the gap of unavailability of miRNA structure data bank. This database aims to facilitate computational data analysis for drug discovery, opening new avenues for advancing technologies, such as machine learning-based predictions in the field of RNA biology.
Conclusion: The publicly accessible structures provided by miRVim, available at https://mirna.in/miRVim, offer a valuable resource for the research community, advancing the field of miRNA-related computational analysis and drug discovery.
{"title":"miRVim: Three-dimensional miRNA Structure Database.","authors":"Vishal Kumar Sahu, Ankita Subhadarsani Parida, Amit Ranjan, Harishkumar Madhyastha, Soumya Basu","doi":"10.2174/0122115366307988240809045125","DOIUrl":"https://doi.org/10.2174/0122115366307988240809045125","url":null,"abstract":"<p><strong>Introduction: </strong>MicroRNAs (miRNAs), a distinct category of non-coding RNAs, exert multifaceted regulatory functions in a variety of organisms, including humans, animals, and plants. The inventory of identified miRNAs stands at approximately 60,000 among all species, and 1,926 in Homo sapiens manifest miRNA expression.</p><p><strong>Method: </strong>Their theranostic role has been explored by researchers over the last few decades, positioning them as prominent therapeutic targets as our understanding of RNA targeting advances. However, the limited availability of experimentally determined miRNA structures has constrained drug discovery efforts relying on virtual screening or computational methods, including machine learning and artificial intelligence.</p><p><strong>Results: </strong>To address this lacuna, miRVim has been developed, providing a repository of human miRNA structures derived from both two-dimensional (MXFold2, CentroidFold, and RNAFold) and three-dimensional (RNAComposer and 3dRNA) structure prediction algorithms, in addition to experimentally available structures from the RCSB PDB repository. miRVim contains 13,971 predicted secondary structures and 17,045 predicted three-dimensional structures, filling the gap of unavailability of miRNA structure data bank. This database aims to facilitate computational data analysis for drug discovery, opening new avenues for advancing technologies, such as machine learning-based predictions in the field of RNA biology.</p><p><strong>Conclusion: </strong>The publicly accessible structures provided by miRVim, available at https://mirna.in/miRVim, offer a valuable resource for the research community, advancing the field of miRNA-related computational analysis and drug discovery.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-25DOI: 10.2174/0122115366320085240716180112
Ma'ayan V Levy, Hannah K Fandl, Jamie G Hijmans, Kelly A Stockelman, Samuel T Ruzzene, Whitney R Reiakvam, Zoe A Goldthwaite, Jared J Greiner, Christopher A DeSouza, Vinicius P Garcia
Introduction/ Objective: Estrogen plays a protective role in vascular health due, in part, to its regulation of endothelial inflammation. However, the mechanism(s) by which estrogen negatively regulates inflammatory signaling pathways is not completely understood. MicroRNAs (miRNAs) are recognized as sensitive and selective regulators of cardiovascular function, inflammation, and disease, yet the effects of 17β-estradiol on the endothelial miRNA profile are largely unknown. The aim of this study was to determine the effect of 17β-estradiol on the expression of inflammation-associated miRNAs in endothelial cells in vitro.
Methods: Human Umbilical Vein Endothelial cells (HUVECs) were treated with media in the absence (control) and presence of 17β-estradiol (100 nM) for 24 hr. Thereafter, endothelial cell release of cytokines (IL-6 and IL-8), the intracellular expression of the central protein inflammatory mediator NF- B, and the levels of inflammatory-associated miRNAs: miR-126, miR-146a, miR-181b, miR-204, and miR-let-7a, were determined.
Results: 17β-estradiol-treated cells released significantly lower levels of IL-6 (47.6±1.5 pg/mL vs 59.3±4.9 pg/mL) and IL-8 (36.3±2.3 pg/mL vs 44.0±2.0 pg/mL). Cellular expression of total NF- B (26.0±2.8 AU vs 21.2±3.1 AU) was not different between groups; however, activated NF- B (Ser536) (12.9±1.7 AU vs 20.2±2.2 AU) was markedly reduced in 17β-estradiol-treated cells as compared to untreated cells. Furthermore, cellular expressions of miR-126 (1.8±0.3 fold), miR-146a (1.7±0.3 fold), miR-181b (2.1±0.4 fold), miR-204 (1.9±0.4 fold), and miR-Let-7a (1.8±0.3 fold) were markedly increased in response to 17β-estradiol treatment.
Conclusion: These data suggest that the anti-inflammatory effect of 17β-estradiol in endothelial cells may be mediated by miRNAs.
导言/目的:雌激素对血管健康起着保护作用,部分原因是它能调节内皮炎症。然而,雌激素负向调节炎症信号通路的机制尚未完全明了。微RNA(miRNA)被认为是心血管功能、炎症和疾病的敏感性和选择性调节因子,然而,17β-雌二醇对内皮miRNA谱的影响在很大程度上是未知的。本研究旨在确定 17β-estradiol 对体外内皮细胞中炎症相关 miRNAs 表达的影响。方法:用无(对照组)和有 17β-estradiol (100 nM)的培养基处理人脐静脉内皮细胞(HUVECs)24 小时。此后,测定内皮细胞释放的细胞因子(IL-6 和 IL-8)、细胞内中心蛋白炎症介质 NF- B 的表达以及炎症相关 miRNAs(miR-126、miR-146a、miR-181b、miR-204 和 miR-let-7a)的水平:结果:17β-雌二醇处理的细胞释放的IL-6(47.6±1.5 pg/mL vs 59.3±4.9 pg/mL)和IL-8(36.3±2.3 pg/mL vs 44.0±2.0 pg/mL)水平明显较低。总NF- B(26.0±2.8 AU vs 21.2±3.1 AU)的细胞表达在组间无差异;然而,与未处理的细胞相比,活化的NF- B(Ser536)(12.9±1.7 AU vs 20.2±2.2 AU)在17β-雌二醇处理的细胞中明显减少。此外,细胞中的miR-126(1.8±0.3倍)、miR-146a(1.7±0.3倍)、miR-181b(2.1±0.4倍)、miR-204(1.9±0.4倍)和miR-Let-7a(1.8±0.3倍)的表达在17β-雌二醇处理后明显增加:这些数据表明,17β-雌二醇对内皮细胞的抗炎作用可能是由miRNAs介导的。
{"title":"Effect of 17β-Estradiol on Endothelial Cell Expression of Inflammation-Related MicroRNA.","authors":"Ma'ayan V Levy, Hannah K Fandl, Jamie G Hijmans, Kelly A Stockelman, Samuel T Ruzzene, Whitney R Reiakvam, Zoe A Goldthwaite, Jared J Greiner, Christopher A DeSouza, Vinicius P Garcia","doi":"10.2174/0122115366320085240716180112","DOIUrl":"https://doi.org/10.2174/0122115366320085240716180112","url":null,"abstract":"<p><p>Introduction/ Objective: Estrogen plays a protective role in vascular health due, in part, to its regulation of endothelial inflammation. However, the mechanism(s) by which estrogen negatively regulates inflammatory signaling pathways is not completely understood. MicroRNAs (miRNAs) are recognized as sensitive and selective regulators of cardiovascular function, inflammation, and disease, yet the effects of 17β-estradiol on the endothelial miRNA profile are largely unknown. The aim of this study was to determine the effect of 17β-estradiol on the expression of inflammation-associated miRNAs in endothelial cells in vitro.</p><p><strong>Methods: </strong>Human Umbilical Vein Endothelial cells (HUVECs) were treated with media in the absence (control) and presence of 17β-estradiol (100 nM) for 24 hr. Thereafter, endothelial cell release of cytokines (IL-6 and IL-8), the intracellular expression of the central protein inflammatory mediator NF- B, and the levels of inflammatory-associated miRNAs: miR-126, miR-146a, miR-181b, miR-204, and miR-let-7a, were determined.</p><p><strong>Results: </strong>17β-estradiol-treated cells released significantly lower levels of IL-6 (47.6±1.5 pg/mL vs 59.3±4.9 pg/mL) and IL-8 (36.3±2.3 pg/mL vs 44.0±2.0 pg/mL). Cellular expression of total NF- B (26.0±2.8 AU vs 21.2±3.1 AU) was not different between groups; however, activated NF- B (Ser536) (12.9±1.7 AU vs 20.2±2.2 AU) was markedly reduced in 17β-estradiol-treated cells as compared to untreated cells. Furthermore, cellular expressions of miR-126 (1.8±0.3 fold), miR-146a (1.7±0.3 fold), miR-181b (2.1±0.4 fold), miR-204 (1.9±0.4 fold), and miR-Let-7a (1.8±0.3 fold) were markedly increased in response to 17β-estradiol treatment.</p><p><strong>Conclusion: </strong>These data suggest that the anti-inflammatory effect of 17β-estradiol in endothelial cells may be mediated by miRNAs.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-25DOI: 10.2174/0122115366305491240708060422
Swastik Mishra, Lakshmi Puzhankara
microRNAs are a family of small, non-coding RNA molecules that can regulate the translation of messenger RNAs (mRNAs). Numerous miRNAs have been proposed as potential indicators for periodontal disease, and their regulation might serve as a potent means of restricting the disease process. MiRNAs act as important immune system regulators that promote the production of many cytokines, including interferon (IFN), tumour necrosis factor (TNF), and IL-1as well as RANK. Investigations pertaining to the use of specific miRNAs as therapeutic agents are underway. They can influence a variety of regulatory organs and target several genes. Additionally, distinct components of the same expression pathway can be controlled by combining miRNAs and their antagonists. In recent years, many miRNA delivery methods have been created for therapeutic applications. Studies pertaining to the role of miRNAs in periodontal disease pathogenesis may pave the way for the use of miRNAs as biomarkers of periodontal disease. A complete understanding of the role of miRNA in periodontal disease and its mechanism of action can pave the way towards therapeutic strategies that can reduce or even prevent the progression of periodontal diseases.
{"title":"Periodontal Tissue Homoeostasis, Immunity, the Red Complex Pathogens, and Dysbiosis: Unraveling the microRNA Effect.","authors":"Swastik Mishra, Lakshmi Puzhankara","doi":"10.2174/0122115366305491240708060422","DOIUrl":"https://doi.org/10.2174/0122115366305491240708060422","url":null,"abstract":"<p><p>microRNAs are a family of small, non-coding RNA molecules that can regulate the translation of messenger RNAs (mRNAs). Numerous miRNAs have been proposed as potential indicators for periodontal disease, and their regulation might serve as a potent means of restricting the disease process. MiRNAs act as important immune system regulators that promote the production of many cytokines, including interferon (IFN), tumour necrosis factor (TNF), and IL-1as well as RANK. Investigations pertaining to the use of specific miRNAs as therapeutic agents are underway. They can influence a variety of regulatory organs and target several genes. Additionally, distinct components of the same expression pathway can be controlled by combining miRNAs and their antagonists. In recent years, many miRNA delivery methods have been created for therapeutic applications. Studies pertaining to the role of miRNAs in periodontal disease pathogenesis may pave the way for the use of miRNAs as biomarkers of periodontal disease. A complete understanding of the role of miRNA in periodontal disease and its mechanism of action can pave the way towards therapeutic strategies that can reduce or even prevent the progression of periodontal diseases.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Molecular markers in Colorectal Cancer (CRC) are needed for more ac-curate classification and personalized treatment. In this way, we investigated the effects of the BRAF gene on clinical outcomes of its expression fluctuations and its polymorphism at rs1267623 in CRC.
Methods: In this study, 36.36 percent of patients with CRC were women, and 63.63 percent were men. After the pathology department confirmed the tumor of the samples, the stage and grade of the tumor were determined according to the TNM system. Real-time PCR was used to check the expression of the BRAF gene in tumor and non-tumor tissues, and its polymorphism in rs1267623 was also checked using the Tetra-ARMs PCR technique.
Results: The expression of BRAF in tumor tissues was significantly higher than in non-tumoral tissues (P = 0.001), indicating an upregulation of BRAF gene expression in tumoral tissues. The user's text is empty. Furthermore, there was a significant correlation between BRAF expression and tumor stage (P = 0.001), as well as tumor grade (P = 0.003). However, no significant link was found between lymph node metastasis and distant metastasis of BRAF gene expression (P = 0.3). Additionally, no mutation was detected in the investigation of rs1267623 polymorphism.
Conclusion: The BRAF gene was upregulated in tumoral tissues. Remarkably, no mutation was found in the rs1267623 polymorphism. As a result, this gene can be used as a biomarker in the diagnosis and treatment of CRC.
{"title":"Evaluation of Fluctuations of BRAF Gene Expression and its Polymorphism at rs1267623 in Colorectal Cancer.","authors":"Seyedeh Elham Norollahi, Kosar Babaei, Sogand Vahidi, Seyed Javad Hosseini Motaz, Mahmoud Kalani Tarbeghan, Mostafa Khaleghipour, Elaheh Asghari Gharakhyli, Seyed Reza Mirhafez, Ali Akbar Samadani","doi":"10.2174/0122115366286360240625095932","DOIUrl":"https://doi.org/10.2174/0122115366286360240625095932","url":null,"abstract":"<p><strong>Background: </strong>Molecular markers in Colorectal Cancer (CRC) are needed for more ac-curate classification and personalized treatment. In this way, we investigated the effects of the BRAF gene on clinical outcomes of its expression fluctuations and its polymorphism at rs1267623 in CRC.</p><p><strong>Methods: </strong>In this study, 36.36 percent of patients with CRC were women, and 63.63 percent were men. After the pathology department confirmed the tumor of the samples, the stage and grade of the tumor were determined according to the TNM system. Real-time PCR was used to check the expression of the BRAF gene in tumor and non-tumor tissues, and its polymorphism in rs1267623 was also checked using the Tetra-ARMs PCR technique.</p><p><strong>Results: </strong>The expression of BRAF in tumor tissues was significantly higher than in non-tumoral tissues (P = 0.001), indicating an upregulation of BRAF gene expression in tumoral tissues. The user's text is empty. Furthermore, there was a significant correlation between BRAF expression and tumor stage (P = 0.001), as well as tumor grade (P = 0.003). However, no significant link was found between lymph node metastasis and distant metastasis of BRAF gene expression (P = 0.3). Additionally, no mutation was detected in the investigation of rs1267623 polymorphism.</p><p><strong>Conclusion: </strong>The BRAF gene was upregulated in tumoral tissues. Remarkably, no mutation was found in the rs1267623 polymorphism. As a result, this gene can be used as a biomarker in the diagnosis and treatment of CRC.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-12DOI: 10.2174/0122115366298799240625115843
Ramin Raoufinia, Parisa Afrasiabi, Amir Dehghanpour, Sara Memarpour, Sayyed Hadi Sayyed Hosseinian, Ehsan Saburi, Karim Naghipoor, Samaneh Rezaei, Meisam Haghmoradi, Neda Keyhanvar, Mehdi Rostami, Farhad Fakoor, Mohammadali Izadpanah Kazemi, Meysam Moghbeli, Hamid Reza Rahimi
Cancer, the second greatest cause of mortality worldwide, frequently causes bone me-tastases in patients with advanced-stage carcinomas such as prostate, breast, and lung cancer. The existence of these metastases contributes to the occurrence of skeletal-related events (SREs), which are defined by excessive pain, pathological fractures, hypercalcemia, and spinal cord com-pression. These injurious incidents leave uncomfortably large holes in each of the cancer patient's life quality. Primary bone cancers, including osteosarcoma (OS), chondrosarcoma (CS), and Ewing's sarcoma (ES), have unclear origins. MicroRNA (miRNA) expression patterns have been changed in primary bone cancers such as OS, CS, and ES, indicating a role in tumor development, invasion, metastasis, and treatment response. These miRNAs are persistent in circulation and ex-hibit distinct patterns in many forms of bone tumors, making them potential biomarkers for early detection and treatment of such diseases. Given their crucial regulatory functions in various bio-logical processes and conditions, including cancer, this study aims to look at miRNAs' activities and possible contributions to bone malignancies, focusing on OS, CS, and ES. In conclusion, miRNAs are valuable tools for diagnosing, monitoring, and predicting OS, CS, and ES outcomes. Further research is required to fully comprehend the intricate involvement of miRNAs in these bone cancers and to develop effective miRNA-based treatments.
{"title":"The Landscape of microRNAs in Bone Tumor: A Comprehensive Review in Recent Studies.","authors":"Ramin Raoufinia, Parisa Afrasiabi, Amir Dehghanpour, Sara Memarpour, Sayyed Hadi Sayyed Hosseinian, Ehsan Saburi, Karim Naghipoor, Samaneh Rezaei, Meisam Haghmoradi, Neda Keyhanvar, Mehdi Rostami, Farhad Fakoor, Mohammadali Izadpanah Kazemi, Meysam Moghbeli, Hamid Reza Rahimi","doi":"10.2174/0122115366298799240625115843","DOIUrl":"https://doi.org/10.2174/0122115366298799240625115843","url":null,"abstract":"<p><p>Cancer, the second greatest cause of mortality worldwide, frequently causes bone me-tastases in patients with advanced-stage carcinomas such as prostate, breast, and lung cancer. The existence of these metastases contributes to the occurrence of skeletal-related events (SREs), which are defined by excessive pain, pathological fractures, hypercalcemia, and spinal cord com-pression. These injurious incidents leave uncomfortably large holes in each of the cancer patient's life quality. Primary bone cancers, including osteosarcoma (OS), chondrosarcoma (CS), and Ewing's sarcoma (ES), have unclear origins. MicroRNA (miRNA) expression patterns have been changed in primary bone cancers such as OS, CS, and ES, indicating a role in tumor development, invasion, metastasis, and treatment response. These miRNAs are persistent in circulation and ex-hibit distinct patterns in many forms of bone tumors, making them potential biomarkers for early detection and treatment of such diseases. Given their crucial regulatory functions in various bio-logical processes and conditions, including cancer, this study aims to look at miRNAs' activities and possible contributions to bone malignancies, focusing on OS, CS, and ES. In conclusion, miRNAs are valuable tools for diagnosing, monitoring, and predicting OS, CS, and ES outcomes. Further research is required to fully comprehend the intricate involvement of miRNAs in these bone cancers and to develop effective miRNA-based treatments.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Glioblastoma Multiforme (GBM) is a prevalent and deadly type of primary astrocytoma, constituting over 60% of adult brain tumors, and has a poor prognosis, with a high relapse rate within 7 months of diagnosis. Despite surgical, radiotherapy, and chemotherapy treatments, GBM remains challenging due to resistance. MicroRNA (miRNAs) control gene expression at transcriptional and post-transcriptional levels by targeting their messenger RNA (mRNA), and also contribute to the development of various neoplasms, including GBM.
Methods: The present study focuses on exploring the miRNAs-based pathogenesis of GBM and evaluating most potential plant-based therapeutic agents with in silico analysis. Gene chips were retrieved from the Gene Expression Omnibus (GEO) database, followed by the Robust- RankAggereg algorithm to determine the Differentially Expressed miRNAs (DEMs). The predicted targets were intersected with the GBM-associated genes, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the overlapping genes was performed. At the same time, five phytochemicals were selected for the Connectivity map (CMap), and the most efficient ones were those that had undergone molecular docking analysis to obtain the potential therapeutic agents.
Results: The hsa-miR-10b, hsa-miR-21, and hsa-miR-15b were obtained, and eight genes were found to be associated with glioma pathways; VSIG4, PROCR, PLAT, and ITGB2 were upregulated while, CAMK2B, PDE1A, GABRA1, and KCNJ6 were downregulated. The drugs Resveratrol and Quercetin were identified as the most prominent drugs.
Conclusion: These miRNAs-based drugs can be used as a curative agent for the treatment of GBM. However, in vivo, experimental data, and clinical trials are necessary to provide an alternative to conventional GBM cancer chemotherapy.
{"title":"Glioblastoma Multiforme miRNA based Comprehensive Study to Validate Phytochemicals for Effective Treatment against Deadly Tumour through In Silico Evaluation.","authors":"Roji Begam Khan, Shikha Tiwai, Aryan Jarkharya, Archana Tiwari, Rashmi Chowdhary, Adesh Shrivastava","doi":"10.2174/0122115366302365240618122812","DOIUrl":"https://doi.org/10.2174/0122115366302365240618122812","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma Multiforme (GBM) is a prevalent and deadly type of primary astrocytoma, constituting over 60% of adult brain tumors, and has a poor prognosis, with a high relapse rate within 7 months of diagnosis. Despite surgical, radiotherapy, and chemotherapy treatments, GBM remains challenging due to resistance. MicroRNA (miRNAs) control gene expression at transcriptional and post-transcriptional levels by targeting their messenger RNA (mRNA), and also contribute to the development of various neoplasms, including GBM.</p><p><strong>Methods: </strong>The present study focuses on exploring the miRNAs-based pathogenesis of GBM and evaluating most potential plant-based therapeutic agents with in silico analysis. Gene chips were retrieved from the Gene Expression Omnibus (GEO) database, followed by the Robust- RankAggereg algorithm to determine the Differentially Expressed miRNAs (DEMs). The predicted targets were intersected with the GBM-associated genes, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the overlapping genes was performed. At the same time, five phytochemicals were selected for the Connectivity map (CMap), and the most efficient ones were those that had undergone molecular docking analysis to obtain the potential therapeutic agents.</p><p><strong>Results: </strong>The hsa-miR-10b, hsa-miR-21, and hsa-miR-15b were obtained, and eight genes were found to be associated with glioma pathways; VSIG4, PROCR, PLAT, and ITGB2 were upregulated while, CAMK2B, PDE1A, GABRA1, and KCNJ6 were downregulated. The drugs Resveratrol and Quercetin were identified as the most prominent drugs.</p><p><strong>Conclusion: </strong>These miRNAs-based drugs can be used as a curative agent for the treatment of GBM. However, in vivo, experimental data, and clinical trials are necessary to provide an alternative to conventional GBM cancer chemotherapy.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.2174/0122115366297817240613065052
Biswadev Mitra, Brendan Major, Jonathan Reyes, Nanda Surendran, Jesse Bain, Lauren Giesler, William T O'Brien, Edmond Sorich, Catherine Willmott, Sandy R Shultz, Terence J O'Brien, Jeffrey V Rosenfeld, Stuart J McDonald
Background: After mild traumatic brain injury (mTBI), some patients experience symptoms that persist for weeks to months. Recovery from mTBI is primarily assessed using selfreported symptom questionnaires. Blood biomarkers, including microRNA species, have shown promise to assist diagnosis of mTBI, however, little is known about how blood microRNA measures might predict symptom recovery.
Objective: The aim of this study was to investigate the variances in plasma microRNAs on the day of injury between individuals with mTBI who report post-concussive symptoms at the 28- day mark and those who do not.
Methods: Patients who presented to an adult, tertiary referral hospital emergency department on the day of the injury and were diagnosed with isolated mTBI (n=35) were followed up for 28 days. Venous blood samples were collected and symptom severity was assessed using the Rivermead Post-Concussion Symptom Questionnaire (RPQ) on the day of injury and at 28 days. Patients who reported ongoing symptoms of total RPQ score ≥10 or at least one symptom severity ≥2, were compared to those with lesser symptom severity or symptom resolution.
Results: There were 9 (25.7%; 95%CI: 12.5-43.3) patients who reported persistent symptoms. Day of injury plasma miR-223-3p levels were significantly higher in individuals with ongoing symptoms compared to those without, however, no such differences were observed for miRs 142- 3p, 423-3p, 32-5p, 144-3p, and let-7f-5p.
Conclusion: Acute plasma miR-223-3p levels appear to detect patients who later have persistent symptoms after mTBI. The results demonstrate the potential utility for such biomarkers to assist in decisions towards early referral for therapy after mTBI.
{"title":"Microrna Biomarkers on Day of Injury Among Patients with Post Concussive Symptoms at 28-Days: A Prospective Cohort Study.","authors":"Biswadev Mitra, Brendan Major, Jonathan Reyes, Nanda Surendran, Jesse Bain, Lauren Giesler, William T O'Brien, Edmond Sorich, Catherine Willmott, Sandy R Shultz, Terence J O'Brien, Jeffrey V Rosenfeld, Stuart J McDonald","doi":"10.2174/0122115366297817240613065052","DOIUrl":"https://doi.org/10.2174/0122115366297817240613065052","url":null,"abstract":"<p><strong>Background: </strong>After mild traumatic brain injury (mTBI), some patients experience symptoms that persist for weeks to months. Recovery from mTBI is primarily assessed using selfreported symptom questionnaires. Blood biomarkers, including microRNA species, have shown promise to assist diagnosis of mTBI, however, little is known about how blood microRNA measures might predict symptom recovery.</p><p><strong>Objective: </strong>The aim of this study was to investigate the variances in plasma microRNAs on the day of injury between individuals with mTBI who report post-concussive symptoms at the 28- day mark and those who do not.</p><p><strong>Methods: </strong>Patients who presented to an adult, tertiary referral hospital emergency department on the day of the injury and were diagnosed with isolated mTBI (n=35) were followed up for 28 days. Venous blood samples were collected and symptom severity was assessed using the Rivermead Post-Concussion Symptom Questionnaire (RPQ) on the day of injury and at 28 days. Patients who reported ongoing symptoms of total RPQ score ≥10 or at least one symptom severity ≥2, were compared to those with lesser symptom severity or symptom resolution.</p><p><strong>Results: </strong>There were 9 (25.7%; 95%CI: 12.5-43.3) patients who reported persistent symptoms. Day of injury plasma miR-223-3p levels were significantly higher in individuals with ongoing symptoms compared to those without, however, no such differences were observed for miRs 142- 3p, 423-3p, 32-5p, 144-3p, and let-7f-5p.</p><p><strong>Conclusion: </strong>Acute plasma miR-223-3p levels appear to detect patients who later have persistent symptoms after mTBI. The results demonstrate the potential utility for such biomarkers to assist in decisions towards early referral for therapy after mTBI.</p>","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}