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Plant MicroRNA Potential in Targeting Sars-CoV-2 Genome Offering Efficient Antiviral MiRNA-Based Therapies. 植物MicroRNA靶向Sars-CoV-2基因组的潜力提供有效的基于MicroRNA的抗病毒治疗
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220818150634
Behzad Hajieghrari, Sara Rahmanian-Koshkaki

Background: In 2019, severe acute respiratory coronavirus II (or SARS-COV-2) emerged in Wuhan, China, rapidly becoming a global pandemic. Coronavirus genus (Coronaviridae) has the largest single-stranded positive-sense RNA genome (~30 kb) among the human infected single-stranded RNA viruses.

Objectives: For the study of active therapeutic plant-derived miRNA(s), it may be possible to uptake the miRNAs and their biological role in the host cell. In this study, we bioinformatically searched plant miRNAs that can potentially interact with the Sars-CoV-2 genome within the 3'- UTR region and have prompt antiviral activity.

Materials and methods: We searched the plant miRNAs that target the 3'-UTR flanking region of the Sars-CoV-2 genome by employing the RNAHybrid, RNA22, and STarMir miRNA/target prediction tools.

Results: The RNAHybrid algorithm found 63 plant miRNAs having hybridization energy with less or equal to -25 kcal.mol-1. Besides, RNA22 and STarMir tools identified eight interactions between the plant miRNAs and the targeted RNA sequence. pvu-miR159a. 2 and sbi-miR5387b were predicted as the most effectively interacting miRNAs in targeting the 3'-UTR sequence, not only by the RNA22 tool but also by the STarMir tool at the same position. However, the GC content of the pvumiR159a. 2 is 55% instead of sbi-miR5387b, which is a GC enriched sequence (71.43%) that may activate TLR receptors.

Conclusion: In our opinion, they are potent plant-derived miRNA candidates that have a great chance of targeting the Sars-CoV-2 genome in the 3'-UTR region in vitro. Therefore, we propose pvu-miR159a.2 for studying antiviral miRNA-based therapies without any essential side effects in vivo.

背景:2019年,严重急性呼吸道冠状病毒II (SARS-COV-2)在中国武汉出现,迅速成为全球大流行。冠状病毒属(冠状病毒科)在人类感染的单链RNA病毒中具有最大的单链正义RNA基因组(~30 kb)。目的:为了研究活性治疗性植物源性miRNA(s),有可能在宿主细胞中摄取miRNA及其生物学作用。在这项研究中,我们从生物信息学上寻找了在3'- UTR区域内可能与Sars-CoV-2基因组相互作用并具有快速抗病毒活性的植物miRNAs。材料和方法:我们利用RNAHybrid、RNA22和STarMir miRNA/靶标预测工具搜索靶向Sars-CoV-2基因组3'-UTR侧翼区域的植物miRNA。结果:RNAHybrid算法发现63个植物mirna的杂交能小于或等于-25 kcal.mol-1。此外,RNA22和STarMir工具鉴定出植物mirna与目标RNA序列之间的8种相互作用。pvu-miR159a。通过RNA22工具和相同位置的STarMir工具预测,2和sbi-miR5387b是靶向3'-UTR序列的最有效的相互作用miRNAs。然而,pvumiR159a的GC含量。2是55%而不是sbi-miR5387b,后者是一个GC富集序列(71.43%),可能激活TLR受体。结论:在我们看来,它们是有效的植物源性miRNA候选物,在体外很有可能靶向Sars-CoV-2基因组的3'-UTR区域。因此,我们提出pvu-miR159a。2 .研究基于mirna的抗病毒疗法,在体内没有任何必要的副作用。
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引用次数: 0
MicroRNAs as Biomarkers for Birth Defects. 作为出生缺陷生物标志物的微RNA。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220215123423
Ratnam S Seelan, M Michele Pisano, Robert M Greene

It is estimated that 2-4% of live births will have a birth defect (BD). The availability of biomarkers for the prenatal detection of BDs will facilitate early risk assessment, prompt medical intervention and ameliorating disease severity. miRNA expression levels are often found to be altered in many diseases. There is, thus, a growing interest in determining whether miRNAs, particularly extracellular miRNAs, can predict, diagnose, or monitor BDs. These miRNAs, typically encapsulated in exosomes, are released by cells (including those of the fetus and placenta) into the extracellular milieu, such as blood, urine, saliva and cerebrospinal fluid, thereby enabling interaction with target cells. Exosomal miRNAs are stable, protected from degradation, and retain functionality. The observation that placental and fetal miRNAs can be detected in maternal serum, provides a strong rationale for adopting miRNAs as noninvasive prenatal biomarkers for BDs. In this mini-review, we examine the current state of research involving the use of miRNAs as prognostic and diagnostic biomarkers for BD.

据估计,2-4% 的活产婴儿会有出生缺陷(BD)。产前检测出生缺陷的生物标志物将有助于早期风险评估、及时的医疗干预和改善疾病的严重程度。因此,人们对确定 miRNA(尤其是细胞外 miRNA)是否能预测、诊断或监测 BDs 越来越感兴趣。这些 miRNA 通常包裹在外泌体中,由细胞(包括胎儿和胎盘的细胞)释放到细胞外环境(如血液、尿液、唾液和脑脊液)中,从而与靶细胞相互作用。外泌体 miRNA 比较稳定,不会被降解,并能保持功能。观察发现胎盘和胎儿 miRNA 可在母体血清中检测到,这为采用 miRNA 作为无创产前生物标记物检测 BDs 提供了强有力的依据。在这篇微型综述中,我们将探讨目前使用 miRNA 作为 BD 预后和诊断生物标志物的研究现状。
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引用次数: 0
Identification of Candidate Immune System MicroRNAs Differentially Found in Colostrum and Milk Exosomes. 初乳和乳外泌体中差异的候选免疫系统microrna鉴定。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220630102316
Poonam Verma, Niharika Mohanty, Babita Pruseth, Sonali Sahoo, Amit Katiyar, Harpreet Singh, Saubhagya Kumar Jena, Rashmi Ranjan Das, Tapas Kumar Som, Sanjeeb Kumar Sahoo, Pranati Nanda, Amit Ghosh

Background: The fetus grows in a sterile womb environment. After birth, the newborn immune system has two immediate hurdles to clear. First immediate suppression of the womb compatible immune system and turn on the immune system of the newborn that can counter the antigenic world. The underlying mechanism of immune fluctuation by milk microRNAs (miRNAs) can be crucial for the treatment of critical or premature newborn.

Methods: We collected fourteen samples of each colostrum and mature milk from lactating mothers, four samples of each were used for microarray analysis, and the other ten were used for miRNA expression profiling by real-time PCR.

Results: From the microarray, 154 differentially expressed miRNAs were identified, whereas 49 miRNAs were revealed as immune-related miRNAs based on a literature study. Among the 49 miRNAs, 33 were already shown as strongly validated immune-related miRNAs (validated by qPCR, Western Blot, and Luciferase assay) and were considered for further analysis. Twenty-two miRNA expressions were analysed by real-time PCR as their Ct values were within considerable limits. Twelve numbers of miRNAs were significantly downregulated in mature milk compared to colostrum, which were again subjected to bioinformatics analysis to predict the biological mechanisms behind the differentially expressed miRNAs.

Conclusion: This study shed light on the human milk exosome miRNA expression dynamics during lactation and their possible role in the gradual skewing of the newborns' immune system. The information is crucial for the development and onset of sepsis in premature newborns in the NICU.

背景:胎儿在无菌子宫环境中生长。出生后,新生儿的免疫系统有两个直接的障碍需要清除。首先,立即抑制子宫相容免疫系统,并启动新生儿的免疫系统,以对抗抗原世界。乳微rna (miRNAs)免疫波动的潜在机制可能对危重新生儿或早产儿的治疗至关重要。方法:从哺乳母亲中各采集初乳和成熟乳各14份样品,各4份样品进行微阵列分析,另外10份样品采用实时PCR技术进行miRNA表达谱分析。结果:从微阵列中鉴定出154个差异表达的mirna,而根据文献研究发现49个mirna是免疫相关的mirna。在49个mirna中,33个已经被证明是强验证的免疫相关mirna(通过qPCR、Western Blot和荧光素酶测定验证),可以考虑进一步分析。实时PCR分析22个miRNA表达,因为它们的Ct值在相当大的范围内。与初乳相比,成熟乳中有12个mirna显著下调,这些mirna再次进行了生物信息学分析,以预测差异表达mirna背后的生物学机制。结论:本研究揭示了哺乳期间母乳外泌体miRNA的表达动态及其在新生儿免疫系统逐渐偏斜中的可能作用。这些信息对于新生儿重症监护病房早产儿脓毒症的发展和发病至关重要。
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引用次数: 1
Prognostic Value and Biological Role of miR-126 in Breast Cancer. miR-126在乳腺癌中的预后价值及生物学作用
Pub Date : 2022-01-01 DOI: 10.2174/1876402914666220428123203
Saiedeh Razi Soofiyani, Kamran Hosseini, Tahereh Ebrahimi, Haleh Forouhandeh, Mohammadreza Sadeghi, Sohrab Minaei Beirami, Tohid Ghasemnejad, Vahideh Tarhriz, Soheila Montazersaheb

In eukaryotic organisms such as humans, some noncoding single-stranded RNAs (ncRNAs) contribute to regulating the expression of some genes before and after the transcription process, which in turn controls a number of vital physiological processes, including cell proliferation, differentiation, invasion, angiogenesis, and embryonic development. miR-126 is one of these miRNAs expressed exclusively in endothelial cells such as capillaries and vessels involved in controlling angiogenesis. In recent years, the link between miRs such as miR-126 and the pathology of breast cancer has attracted the attention of many researchers. Numerous studies have shown that miR-126 may be able to suppress tumor tissue metastasis or to increase tumor metastasis through complex molecular mechanisms. There is ample clinical evidence that miR-126 can be used as a biomarker to predict and diagnose breast cancer due to the increased or decreased expression of certain genes in breast cancer tissue. In this review, we discuss the association between the growth and metastasis (tumorigenesis) of breast cancer and miR-126, as well as the relationship between current research advances in the prognosis, diagnosis, and treatment of breast cancer and miR-126.

在人类等真核生物中,一些非编码单链rna (ncRNAs)在转录过程前后调节一些基因的表达,从而控制许多重要的生理过程,包括细胞增殖、分化、侵袭、血管生成和胚胎发育。miR-126是这些mirna中的一种,仅在内皮细胞(如毛细血管)中表达,参与控制血管生成。近年来,miR-126等miRs与乳腺癌病理之间的联系引起了许多研究者的关注。大量研究表明,miR-126可能通过复杂的分子机制抑制肿瘤组织转移或增加肿瘤转移。大量的临床证据表明,由于乳腺癌组织中某些基因的表达增加或减少,miR-126可以作为预测和诊断乳腺癌的生物标志物。在这篇综述中,我们讨论了miR-126与乳腺癌生长和转移(肿瘤发生)的关系,以及乳腺癌预后、诊断和治疗的研究进展与miR-126的关系。
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引用次数: 4
Diagnostic Value of Potential MicroRNAs in CRC: A Meta-Analysis. 潜在microrna在CRC中的诊断价值:一项荟萃分析。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220523103316
Sofia Fathi, Fadila Guessous, Mehdi Karkouri

Background: MicroRNAs (miRNAs) are small noncoding RNA molecules involved in the post-transcriptional regulation of genes. Deregulated expression of miRNAs is involved in different pathogenic mechanisms, particularly colorectal cancer (CRC) carcinogenesis. Due to their stability and accessibility, circulating miRNAs represent a new family of biomarkers with great potential. Therefore, certain miRNAs can be used as diagnostic biomarkers in CRC.

Objective: This systematic analysis aimed to explore the individual efficacy of the most investigated blood-based miRNAs for CRC diagnosis, namely miR-21, miR-29a and miR-92a.

Methods: Articles were retrieved from databases such as PubMed and Google Scholar, and studies designed to evaluate the diagnostic value of microRNAs in CRC were then selected. We subsequently explored the diagnostic accuracy of each miRNA using parameters such as (SE, SPE, PLR, NLR). The meta-analysis was performed using the Review Manager (Revman) 5.4 software and the Meta Disc software.

Results: Our results suggested that serum miR-21 levels showed great potential as a diagnostic molecular marker. The overall pooled results for sensitivity, specificity, area under the curve (AUC), PLR, and NLR were 78%, 91%, 0.9519, 8.12 and 0.17, respectively.

Conclusion: miRNAs have become increasingly important in the diagnosis of CRC. Based on these findings, circulating miR-21 levels may have a potential value for early detection and might be used as a novel diagnostic biomarker for CRC.

背景:MicroRNAs (miRNAs)是参与基因转录后调控的小非编码RNA分子。mirna的表达失调参与了不同的致病机制,特别是结直肠癌(CRC)的癌变。由于其稳定性和可及性,循环mirna代表了一个具有巨大潜力的新生物标志物家族。因此,某些mirna可作为结直肠癌的诊断性生物标志物。目的:本系统分析旨在探讨研究最多的基于血液的mirna,即miR-21、miR-29a和miR-92a在结直肠癌诊断中的个体疗效。方法:从PubMed和Google Scholar等数据库中检索文章,然后选择旨在评估microrna在CRC中的诊断价值的研究。随后,我们使用(SE, SPE, PLR, NLR)等参数探讨了每个miRNA的诊断准确性。Meta分析采用Review Manager (Revman) 5.4软件和Meta Disc软件进行。结果:我们的研究结果表明血清miR-21水平作为诊断分子标志物具有很大的潜力。敏感性、特异性、曲线下面积(AUC)、PLR和NLR的综合结果分别为78%、91%、0.9519、8.12和0.17。结论:mirna在结直肠癌的诊断中越来越重要。基于这些发现,循环miR-21水平可能具有早期检测的潜在价值,并可能作为CRC的一种新的诊断生物标志物。
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引用次数: 2
MicroRNA-16 Represses TGF-β1-induced Epithelial-to-Mesenchymal Transition in Human Lung Adenocarcinoma Cell Line. MicroRNA-16抑制TGF-β1诱导的人肺腺癌细胞上皮向间质转化
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220826124058
Subbiah Rajasekaran, Sehal Mishra, Deepa Gandhi

Background: The transforming growth factor-beta1 (TGF-β1)-induced epithelial-tomesenchymal transition (EMT) has a crucial effect on the progression and metastasis of lung cancer cells.

Objective: The purpose of this study was to investigate whether microRNA (miR)-16 can suppress TGF-β1-induced EMT and proliferation in human lung adenocarcinoma cell line (A549).

Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-16. The hallmarks of EMT were assessed by RT-qPCR, Western blotting, and cell proliferation assay. A bioinformatics tool was used to identify the putative target of miR-16. The activation of TGF-β1/Smad3 signaling was analysed using Western blotting.

Results: Our results showed that miR-16 expression was significantly down-regulated by TGF-β1 in A549 cells. Moreover, agomir of miR-16 suppressed TGF-β1-induced EMT and cell proliferation. Computational algorithms predicted that the 3'-untranslated regions (3'-UTRs) of Smad3 are direct targets of miR-16. In addition, miR-16 mimic was found to inhibit the TGF-β1-induced activation of the TGF-β1/Smad3 pathway, suggesting that miR-16 may function partly through regulating Smad3.

Conclusion: Our results demonstrated that overexpression of miR-16 suppressed the expression and activation of Smad3, and ultimately inhibited TGF-β1-induced EMT and proliferation in A549 cells. The present findings support further investigation of the anti-cancer effect of miR-16 in animal models of lung cancer to validate the therapeutic potential.

背景:转化生长因子-β1 (TGF-β1)诱导的上皮-间充质转化(EMT)在肺癌细胞的进展和转移中起着至关重要的作用。目的:探讨microRNA (miR)-16是否能抑制TGF-β1诱导的人肺腺癌细胞(A549)的EMT和增殖。方法:采用实时定量聚合酶链反应(RT-qPCR)检测miR-16的表达。通过RT-qPCR、Western blotting和细胞增殖试验评估EMT的特征。使用生物信息学工具鉴定miR-16的假定靶点。Western blotting分析TGF-β1/Smad3信号的激活情况。结果:我们的研究结果显示TGF-β1在A549细胞中显著下调miR-16的表达。此外,miR-16的agomir抑制TGF-β1诱导的EMT和细胞增殖。计算算法预测Smad3的3'-未翻译区(3'- utr)是miR-16的直接靶点。此外,miR-16 mimic被发现抑制TGF-β1诱导的TGF-β1/Smad3通路的激活,提示miR-16可能部分通过调节Smad3发挥作用。结论:我们的研究结果表明,过表达miR-16抑制Smad3的表达和激活,最终抑制TGF-β1诱导的A549细胞EMT和增殖。本研究结果支持进一步研究miR-16在肺癌动物模型中的抗癌作用,以验证其治疗潜力。
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引用次数: 1
P68 RNA Helicase (DDX5) Required for the Formation of Various Specific and Mature miRNA Active RISC Complexes. 形成各种特异性和成熟的miRNA活性RISC复合物所需的P68 RNA螺旋酶(DDX5)。
Pub Date : 2022-01-01 DOI: 10.2174/2211536611666220218121640
Mariette Kokolo, Montse Bach-Elias

Introduction: DEAD-box RNA helicases catalyze the ATP-dependent unwinding of doublestranded RNA. In addition, they are required for protein displacement and remodelling of RNA or RNA/protein complexes. P68 RNA helicase regulates the alternative splicing of the important protooncogene H-Ras, and numerous studies have shown that p68 RNA helicase is probably involved in miRNA biogenesis, mainly through Drosha and RISC/DICER complexes.

Objective: This study aimed to determine how p68 RNA helicase affects the activity of selected mature miRNAs, including miR-342, miR-330, miR-138 and miR-206, miR-126, and miR-335, and let-7a, which are known to be related to cancer processes.

Methods: The miRNA levels were analyzed in stable HeLa cells containing p68 RNA helicase RNAi induced by doxycycline (DOX). Relevant results were repeated using transient transfection with pSuper/ pSuper-p68 RNA helicase RNAi to avoid DOX interference.

Results: Herein, we reported that p68 RNA helicase downregulation increases the accumulation of the mature miRNAs, such as miR-126, let-7a, miR-206, and miR-138. Interestingly, the accumulation of these mature miRNAs does not downregulate their known protein targets, thus suggesting that p68 RNA helicase is required for mature miRNA-active RISC complex activity.

Conclusion: Furthermore, we demonstrated that this requirement is conserved, as drosophila p68 RNA helicase can complete the p68 RNA helicase depleted activity in human cells. Dicer and Drosha proteins are not affected by the downregulation of p68 RNA helicase despite the fact that Dicer is also localized in the nucleus when p68 RNA helicase activity is reduced.

引言:DEAD-box RNA解旋酶催化双链RNA的ATP依赖性解链。此外,它们是RNA或RNA/蛋白质复合物的蛋白质置换和重塑所必需的。p68RNA解旋酶调节重要原癌基因H-Ras的选择性剪接,大量研究表明,p68RNA解旋酶可能主要通过Drosha和RISC/DICER复合物参与miRNA的生物发生。目的:本研究旨在确定p68RNA解旋酶如何影响所选成熟miRNA的活性,包括miR-342、miR-330、miR-138和miR-206、miR-126和miR-335以及let-7a,这些已知与癌症过程有关。方法:在多西环素(DOX)诱导的含有p68RNA解旋酶RNAi的稳定HeLa细胞中分析miRNA水平。使用pSuper/pSuper-p68RNA解旋酶RNAi的瞬时转染重复相关结果以避免DOX干扰。结果:在此,我们报道了p68RNA解旋酶下调增加了成熟miRNA的积累,如miR-126、let-7a、miR-206和miR-138。有趣的是,这些成熟miRNA的积累并没有下调其已知的蛋白质靶标,因此表明p68RNA解旋酶是成熟miRNA活性RISC复合物活性所必需的。结论:此外,我们证明了这一要求是保守的,因为果蝇p68RNA解旋酶可以在人类细胞中完成p68RNA螺旋酶缺失的活性。Dicer和Drosha蛋白不受p68RNA解旋酶下调的影响,尽管当p68RNA解旋酶活性降低时Dicer也定位在细胞核中。
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引用次数: 2
Meet the Editorial Board Member 会见编辑委员会成员
Pub Date : 2021-12-01 DOI: 10.2174/221153661004211231212125
K. Dua
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引用次数: 0
Meet the Associate Editor 与副主编见面
Pub Date : 2021-03-01 DOI: 10.2174/221153661001210820092316
W. Tam
{"title":"Meet the Associate Editor","authors":"W. Tam","doi":"10.2174/221153661001210820092316","DOIUrl":"https://doi.org/10.2174/221153661001210820092316","url":null,"abstract":"","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47890346","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
Preface 前言
Pub Date : 2021-03-01 DOI: 10.2174/221153661001210820091622
Alberto Izzotti
{"title":"Preface","authors":"Alberto Izzotti","doi":"10.2174/221153661001210820091622","DOIUrl":"https://doi.org/10.2174/221153661001210820091622","url":null,"abstract":"","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43183135","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
期刊
MicroRNA (Shariqah, United Arab Emirates)
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