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Identification of miR-20a as a Diagnostic and Prognostic Biomarker in Colorectal Cancer: MicroRNA Sequencing and Machine Learning Analysis. 鉴定 miR-20a 作为结直肠癌诊断和预后生物标记物:MicroRNA 测序和机器学习分析。
Pub Date : 2024-09-24 DOI: 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.

导言:miRNA是许多细胞信号通路的关键调控因子,在各种恶性肿瘤中的差异表达已被研究,并可能在包括结直肠癌(CRC)在内的癌症进展中发挥重要作用:本研究利用机器学习和基因相互作用研究工具来探讨 miRNAs 在 CRC 中的预后和诊断价值。研究人员从 TCGA 数据库中获取了 353 个 CRC 样本和正常组织的整合分析数据,并使用 R 软件包对这些数据进行了进一步分析,从而确定了递延表达的 miRNAs(DEMs)。此外,机器学习和卡普兰-梅耶尔生存分析有助于更好地明确 miRNA 的重要预后价值。然后,结合在线数据库评估了靶基因之间的相互作用、其分子通路以及 DEMs 之间的相关性:结果:研究结果表明,miR-19b和miR-20a具有重要的预后作用,与CRC的进展相关。ROC曲线分析发现,miR-20a单独或与其他miRNA(包括hsa-mir-21和hsa-mir-542)结合,都是CRC的诊断生物标志物。此外,研究还发现 NTRK2、CDC42、表皮生长因子受体、AGO2、PRKCA、HSP90AA1、TLR4、IGF1、ESR1、SMAD2、SMAD4 和 NEDD4L 等 12 个基因是这些 miRNA 的最高得分靶标。通路分析确定了与关键相互作用基因(即表皮生长因子受体、CDC42 和 HSP90AA1)相关的两个酪氨酸激酶和 MAPK 信号通路:为了更好地界定这些 miRNAs 的作用,还编制了包括 lncRNAs 在内的 ceRNA 网络。总之,R数据分析与机器学习的结合为解决miRNA与其靶标之间复杂的相互作用提供了一种稳健的方法。
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引用次数: 0
The Potential Role of Curcumin as a Regulator of microRNA in Colorectal Cancer: A Systematic Review. 姜黄素作为微 RNA 调节剂在结直肠癌中的潜在作用:系统综述
Pub Date : 2024-09-12 DOI: 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.

简介姜黄素是莪术根茎中的一种生物活性成分。姜黄素以其化学预防和抗癌特性而闻名。然而,姜黄素在结直肠癌治疗中的抗癌机制尚不清楚,一些研究表明,许多微RNA(miRs)可能是姜黄素在结直肠癌(CRC)治疗中的潜在靶点,因此有必要对其进行整合和澄清:我们使用一些相关关键词系统地检索了截至 2021 年 7 月的国际数据库,包括 PubMed、Scopus 和 Web of Science:结果:共检索到 87 篇论文,其中相关文章 18 篇。研究发现,姜黄素能上调 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 和 miR-15a,下调 miR-21、miR-155、miR-221、miR-222、miR-17-5p、miR-130a、miR-27 和 miR-20a:本综述研究表明,姜黄素可以通过改变 miRs 的表达水平作为治疗 CRC 的新型药物。
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引用次数: 0
Identification of Hub Genes and Analysis of their Regulatory miRNAs in Patients with Thymoma Associated Myasthenia Gravis Based on TCGA Database. 基于 TCGA 数据库鉴定胸腺瘤相关性肌无力患者的枢纽基因并分析其调控 miRNA。
Pub Date : 2024-08-26 DOI: 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。
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引用次数: 0
miRVim: Three-dimensional miRNA Structure Database. miRVim:三维 miRNA 结构数据库。
Pub Date : 2024-08-20 DOI: 10.2174/0122115366307988240809045125
Vishal Kumar Sahu, Ankita Subhadarsani Parida, Amit Ranjan, Harishkumar Madhyastha, Soumya Basu

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.

引言微RNA(miRNA)是一类独特的非编码RNA,在包括人类、动物和植物在内的多种生物体中发挥着多方面的调控功能。在所有物种中,已发现的 miRNA 约有 60,000 个,而在智人中,有 1,926 个表现为 miRNA 表达:方法:过去几十年来,研究人员一直在探索 miRNA 的治疗作用,随着我们对 RNA 靶向认识的不断深入,miRNA 已成为重要的治疗靶点。然而,由于通过实验确定的 miRNA 结构有限,依赖虚拟筛选或计算方法(包括机器学习和人工智能)的药物发现工作受到限制:为了弥补这一空白,我们开发了 miRVim,它提供了一个人类 miRNA 结构库,这些结构来自二维(MXFold2、CentroidFold 和 RNAFold)和三维(RNAComposer 和 3dRNA)结构预测算法,此外还有来自 RCSB PDB 库的实验可用结构。该数据库旨在促进药物发现的计算数据分析,为 RNA 生物学领域基于机器学习的预测等先进技术开辟新的途径:可在 https://mirna.in/miRVim 上公开访问的 miRVim 提供的结构为研究界提供了宝贵的资源,推动了 miRNA 相关计算分析和药物发现领域的发展。
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引用次数: 0
Effect of 17β-Estradiol on Endothelial Cell Expression of Inflammation-Related MicroRNA. 17β-雌二醇对内皮细胞表达炎症相关 MicroRNA 的影响
Pub Date : 2024-07-25 DOI: 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。
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引用次数: 0
Periodontal Tissue Homoeostasis, Immunity, the Red Complex Pathogens, and Dysbiosis: Unraveling the microRNA Effect. 牙周组织稳态、免疫、红色复合病原体和菌群失调:揭示 microRNA 的影响。
Pub Date : 2024-07-25 DOI: 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.

microRNAs是一种小型非编码RNA分子,可以调节信使RNAs(mRNAs)的翻译。许多 miRNA 被认为是牙周病的潜在指标,对它们的调节可能是限制疾病进程的有效手段。miRNA 是重要的免疫系统调节因子,可促进多种细胞因子的产生,包括干扰素(IFN)、肿瘤坏死因子(TNF)、IL-1 和 RANK。有关使用特定 miRNA 作为治疗药物的研究正在进行中。它们可以影响多种调节器官,并以多个基因为靶标。此外,通过结合 miRNA 及其拮抗剂,可以控制同一表达途径的不同成分。近年来,许多用于治疗的 miRNA 递送方法应运而生。有关 miRNA 在牙周病发病机制中作用的研究可能会为使用 miRNA 作为牙周病的生物标志物铺平道路。全面了解 miRNA 在牙周病中的作用及其作用机制,可以为制定治疗策略铺平道路,从而减少甚至预防牙周病的发展。
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引用次数: 0
Evaluation of Fluctuations of BRAF Gene Expression and its Polymorphism at rs1267623 in Colorectal Cancer. 评估结直肠癌中 BRAF 基因表达的波动及其 rs1267623 的多态性
Pub Date : 2024-07-12 DOI: 10.2174/0122115366286360240625095932
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

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.

背景:结直肠癌(CRC)需要分子标记物来进行更准确的分类和个性化治疗。为此,我们研究了 BRAF 基因的表达波动及其 rs1267623 多态性对 CRC 临床结果的影响:本研究中,36.36%的 CRC 患者为女性,63.63%为男性。样本经病理科确诊后,根据 TNM 系统确定肿瘤的分期和分级。采用实时 PCR 技术检测肿瘤和非肿瘤组织中 BRAF 基因的表达,并采用 Tetra-ARMs PCR 技术检测其 rs1267623 的多态性:结果:BRAF在肿瘤组织中的表达明显高于非肿瘤组织(P=0.001),表明BRAF基因在肿瘤组织中表达上调。用户文本为空。此外,BRAF表达与肿瘤分期(P = 0.001)和肿瘤分级(P = 0.003)之间存在明显相关性。然而,BRAF基因表达的淋巴结转移和远处转移之间没有发现明显联系(P = 0.3)。此外,在调查rs1267623多态性时未发现突变:结论:BRAF基因在肿瘤组织中上调。结论:BRAF 基因在肿瘤组织中上调,值得注意的是,在 rs1267623 多态性中未发现突变。因此,该基因可作为诊断和治疗 CRC 的生物标志物。
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引用次数: 0
The Landscape of microRNAs in Bone Tumor: A Comprehensive Review in Recent Studies. 骨肿瘤中的 microRNAs:最新研究综述
Pub Date : 2024-07-12 DOI: 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.

癌症是全球第二大死亡原因,在前列腺癌、乳腺癌和肺癌等晚期癌症患者中,癌症经常会导致骨转移。这些转移灶的存在导致了骨骼相关事件(SREs)的发生,即过度疼痛、病理性骨折、高钙血症和脊髓压迫。这些伤害性事件给每位癌症患者的生活质量都留下了令人不舒服的大漏洞。包括骨肉瘤(OS)、软骨肉瘤(CS)和尤文肉瘤(ES)在内的原发性骨癌起源不清。原发性骨癌(如 OS、CS 和 ES)中的微 RNA(miRNA)表达模式发生了变化,表明它们在肿瘤发生、侵袭、转移和治疗反应中发挥作用。这些 miRNA 在血液循环中持续存在,并在多种形式的骨肿瘤中表现出不同的模式,使其成为早期检测和治疗此类疾病的潜在生物标志物。鉴于miRNAs在包括癌症在内的各种生物逻辑过程和条件中的重要调控功能,本研究旨在研究miRNAs的活性及其对骨恶性肿瘤的可能贡献,重点关注OS、CS和ES。总之,miRNA 是诊断、监测和预测 OS、CS 和 ES 结果的重要工具。要全面了解 miRNA 在这些骨癌中的复杂参与,并开发基于 miRNA 的有效治疗方法,还需要进一步的研究。
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引用次数: 0
Glioblastoma Multiforme miRNA based Comprehensive Study to Validate Phytochemicals for Effective Treatment against Deadly Tumour through In Silico Evaluation. 基于多形性胶质母细胞瘤 miRNA 的综合研究,通过硅学评估验证植物化学物质对致命肿瘤的有效治疗。
Pub Date : 2024-07-08 DOI: 10.2174/0122115366302365240618122812
Roji Begam Khan, Shikha Tiwai, Aryan Jarkharya, Archana Tiwari, Rashmi Chowdhary, Adesh Shrivastava

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.

背景:多形性胶质母细胞瘤(GBM多形性胶质母细胞瘤(GBM)是一种常见且致命的原发性星形细胞瘤,占成人脑肿瘤的60%以上,预后不良,确诊后7个月内复发率很高。尽管采用了手术、放疗和化疗等治疗方法,但由于耐药性的存在,GBM 的治疗仍然具有挑战性。微小RNA(miRNA)通过靶向信使RNA(mRNA)在转录和转录后水平控制基因表达,也有助于包括GBM在内的各种肿瘤的发展:本研究的重点是探索基于 miRNAs 的 GBM 发病机制,并通过硅学分析评估大多数潜在的植物治疗药物。从基因表达总库(GEO)数据库中检索基因芯片,然后使用 Robust- RankAggereg 算法确定差异表达的 miRNAs(DEMs)。将预测的靶标与 GBM 相关基因进行交叉,并对重叠基因进行基因本体(GO)和京都基因组百科全书(KEGG)富集分析。同时,选择了五种植物化学物质进行连接图谱(CMap)分析,并对其中最有效的植物化学物质进行了分子对接分析,以获得潜在的治疗药物:结果:得到了 hsa-miR-10b、hsa-miR-21 和 hsa-miR-15b,并发现了 8 个与胶质瘤通路相关的基因:VSIG4、PROCR、PLAT 和 ITGB2 上调,而 CAMK2B、PDE1A、GABRA1 和 KCNJ6 下调。白藜芦醇和槲皮素被确定为最主要的药物:结论:这些基于 miRNAs 的药物可作为治疗 GBM 的药物。结论:这些基于 miRNAs 的药物可作为治疗 GBM 的药物,但还需要体内实验数据和临床试验来提供传统 GBM 癌症化疗的替代方案。
{"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}
引用次数: 0
Microrna Biomarkers on Day of Injury Among Patients with Post Concussive Symptoms at 28-Days: A Prospective Cohort Study. 脑震荡后 28 天症状患者受伤当天的微纳生物标志物:前瞻性队列研究
Pub Date : 2024-07-08 DOI: 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.

背景:轻度创伤性脑损伤(mTBI)后,一些患者会出现持续数周至数月的症状。轻微创伤性脑损伤后的恢复情况主要通过自述症状问卷进行评估。血液生物标志物,包括微RNA种类,已显示出协助诊断mTBI的前景,然而,人们对血液微RNA测量如何预测症状恢复知之甚少:本研究旨在调查在受伤 28 天时报告出现脑震荡后症状的 mTBI 患者与未报告出现脑震荡后症状的患者之间在受伤当天血浆 microRNA 的差异:方法: 对受伤当天到成人三级转诊医院急诊科就诊并被诊断为孤立性 mTBI 的患者(n=35)进行为期 28 天的随访。采集静脉血液样本,并在受伤当天和28天后使用Rivermead脑震荡后症状问卷(RPQ)评估症状严重程度。将 RPQ 总分≥10 分或至少一种症状严重程度≥2 分的持续症状患者与症状严重程度较轻或症状缓解的患者进行比较:有 9 名患者(25.7%;95%CI:12.5-43.3)报告了持续症状。与没有持续症状的患者相比,受伤当天血浆 miR-223-3p 水平明显较高,但 miRs 142-3p、423-3p、32-5p、144-3p 和 let-7f-5p 没有观察到这种差异:结论:急性血浆 miR-223-3p 水平似乎能检测出 mTBI 后出现持续症状的患者。结论:急性血浆 miR-223-3p 水平似乎能检测出 mTBI 后出现持续症状的患者,这些结果表明,此类生物标志物具有潜在的实用性,可帮助做出早期转诊治疗的决定。
{"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}
引用次数: 0
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MicroRNA (Shariqah, United Arab Emirates)
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