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Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update. 以 miRNA 和其他非编码 RNA 为靶标的治疗方法:最新进展。
IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-04-13 DOI: 10.3390/ncrna9020027
Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo

Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression, and because miRNAs act as tumor suppressors or oncogenes (oncomiRs), they have emerged as attractive tools and, more importantly, as a new class of targets for drug development in cancer therapeutics. With the use of miRNA mimics or molecules targeting miRNAs (i.e., small-molecule inhibitors such as anti-miRS), these therapeutics have shown promise in preclinical settings. Some miRNA-targeted therapeutics have been extended to clinical development, such as the mimic of miRNA-34 for treating cancer. Here, we discuss insights into the role of miRNAs and other non-coding RNAs in tumorigenesis and resistance and summarize some recent successful systemic delivery approaches and recent developments in miRNAs as targets for anticancer drug development. Furthermore, we provide a comprehensive overview of mimics and inhibitors that are in clinical trials and finally a list of clinical trials based on miRNAs.

miRNA 参与并被描述为癌症主要特征的主调节因子,包括细胞分化、增殖、存活、细胞周期、侵袭和转移。实验数据表明,癌症表型可以通过靶向 miRNA 表达来改变,而且由于 miRNAs 可作为肿瘤抑制因子或致癌基因(oncomiRs),它们已成为具有吸引力的工具,更重要的是,它们已成为癌症治疗药物开发的一类新靶点。通过使用 miRNA 模拟物或靶向 miRNA 的分子(即小分子抑制剂,如 anti-miRS),这些疗法在临床前研究中已显示出前景。一些 miRNA 靶向疗法已进入临床开发阶段,如用于治疗癌症的 miRNA-34 模拟物。在此,我们将深入探讨 miRNA 和其他非编码 RNA 在肿瘤发生和抗药性中的作用,并总结最近一些成功的系统给药方法以及 miRNA 作为抗癌药物开发靶点的最新进展。此外,我们还全面概述了正在进行临床试验的模拟物和抑制剂,最后列出了基于 miRNAs 的临床试验清单。
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引用次数: 0
LncRNA PNKY Is Upregulated in Breast Cancer and Promotes Cell Proliferation and EMT in Breast Cancer Cells. LncRNA PNKY在乳腺癌中表达上调,促进乳腺癌细胞增殖和EMT
IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-04-06 DOI: 10.3390/ncrna9020025
Forough Hakiminia, Firooz Jannat Alipoor, Mostafa Keshavarz, Malek Hossein Asadi

Long non-coding RNAs (lncRNAs) are known to be important regulators in different cellular processes and are implicated in various human diseases. Recently, lncRNA PNKY has been found to be involved in pluripotency and differentiation of embryonic and postnatal neural stem cells (NSCs); however, its expression and function in cancer cells is still unclear. In the present study, we observed the expression of PNKY in various cancer tissues, including brain, breast, colorectal, and prostate cancers. In particular, we demonstrated that lncRNA PNKY was significantly upregulated in breast tumors, especially high-grade tumors. Knock down experiments indicated that the suppression of PNKY in breast cancer cells could restrict their proliferation by promoting apoptosis, senescence, and cell cycle disruption. Moreover, the results demonstrated that PNKY may play a crucial role in the cell migration of breast cancer cells. We further found that PNKY may trigger EMT in breast cancer cells by upregulating miR-150 and restricting the expression of Zeb1 and Snail. This study is the first to provide new evidence on the expression and biological function of PNKY in cancer cells and its potential contribution to tumor growth and metastasis.

已知长链非编码rna (lncRNAs)在不同的细胞过程中是重要的调节因子,并与各种人类疾病有关。最近,lncRNA PNKY被发现参与胚胎和出生后神经干细胞(NSCs)的多能性和分化;然而,其在癌细胞中的表达和功能尚不清楚。在本研究中,我们观察了PNKY在各种癌症组织中的表达,包括脑癌、乳腺癌、结直肠癌和前列腺癌。特别是,我们证明lncRNA PNKY在乳腺肿瘤,特别是高级别肿瘤中显著上调。敲低实验表明,PNKY在乳腺癌细胞中的抑制可以通过促进细胞凋亡、衰老和细胞周期破坏来限制其增殖。此外,结果表明PNKY可能在乳腺癌细胞的细胞迁移中起关键作用。我们进一步发现,PNKY可能通过上调miR-150并抑制Zeb1和Snail的表达而触发乳腺癌细胞的EMT。本研究首次为PNKY在肿瘤细胞中的表达、生物学功能及其在肿瘤生长和转移中的潜在作用提供了新的证据。
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引用次数: 0
Liquid Biopsies Poorly miRror Renal Ischemia-Reperfusion Injury. 液体活检不能很好地反映肾缺血再灌注损伤。
IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-04-01 DOI: 10.3390/ncrna9020024
Adaysha C Williams, Vaishali Singh, Pengyuan Liu, Alison J Kriegel

Acute kidney injury (AKI) is the rapid reduction in renal function. It is often difficult to detect at an early stage. Biofluid microRNAs (miRs) have been proposed as novel biomarkers due to their regulatory role in renal pathophysiology. The goal of this study was to determine the overlap in AKI miRNA profiles in the renal cortex, urine, and plasma samples collected from a rat model of ischemia-reperfusion (IR)-induced AKI. Bilateral renal ischemia was induced by clamping the renal pedicles for 30 min, followed by reperfusion. Urine was then collected over 24 h, followed by terminal blood and tissue collection for small RNA profiling. Differentially expressed (IR vs. sham) miRs within the urine and renal cortex sample types demonstrated a strong correlation in normalized abundance regardless of injury (IR and sham: R2 = 0.8710 and 0.9716, respectively). Relatively few miRs were differentially expressed in multiple samples. Further, there were no differentially expressed miRs with clinically relevant sequence conservation common between renal cortex and urine samples. This project highlights the need for a comprehensive analysis of potential miR biomarkers, including analysis of pathological tissues and biofluids, with the goal of identifying the cellular origin of altered miRs. Analysis at earlier timepoints is needed to further evaluate clinical potential.

急性肾损伤是指肾功能的迅速下降。它通常很难在早期发现。由于其在肾脏病理生理中的调节作用,生物流体microRNAs (miRs)已被提出作为一种新的生物标志物。本研究的目的是确定从缺血再灌注(IR)诱导的AKI大鼠模型中收集的肾皮质、尿液和血浆样本中AKI miRNA谱的重叠。采用夹紧肾蒂30min后再灌注的方法诱导双侧肾缺血。然后在24小时内收集尿液,随后收集末期血液和组织进行小RNA分析。尿和肾皮质样品类型中的差异表达(IR vs. sham) mir在归一化丰度上表现出很强的相关性,无论损伤如何(IR和sham: R2分别= 0.8710和0.9716)。相对较少的mir在多个样本中存在差异表达。此外,在肾皮质和尿液样本之间没有常见的具有临床相关序列保守性的差异表达miRs。该项目强调需要对潜在的miR生物标志物进行全面分析,包括对病理组织和生物流体的分析,目的是确定改变的miR的细胞起源。需要在更早的时间点进行分析,以进一步评估临床潜力。
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引用次数: 0
CircRNAs and RNA-Binding Proteins Involved in the Pathogenesis of Cancers or Central Nervous System Disorders. 涉及癌症或中枢神经系统疾病发病机制的 CircRNA 和 RNA 结合蛋白。
IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-31 DOI: 10.3390/ncrna9020023
Yuka Ikeda, Sae Morikawa, Moeka Nakashima, Sayuri Yoshikawa, Kurumi Taniguchi, Haruka Sawamura, Naoko Suga, Ai Tsuji, Satoru Matsuda

Circular RNAs (circRNAs), a newly recognized group of noncoding RNA transcripts, have established widespread attention due to their regulatory role in cell signaling. They are covalently closed noncoding RNAs that form a loop, and are typically generated during the splicing of precursor RNAs. CircRNAs are key post-transcriptional and post-translational regulators of gene expression programs that might influence cellular response and/or function. In particular, circRNAs have been considered to function as sponges of specific miRNA, regulating cellular processes at the post-transcription stage. Accumulating evidence has shown that the aberrant expression of circRNAs could play a key role in the pathogenesis of several diseases. Notably, circRNAs, microRNAs, and several RNA-binding proteins, including the antiproliferative (APRO) family proteins, could be indispensable gene modulators, which might be strongly linked to the occurrence of diseases. In addition, circRNAs have attracted general interest for their stability, abundance in the brain, and their capability to cross the blood-brain barrier. Here, we present the current findings and theragnostic potentials of circRNAs in several diseases. With this, we aim to provide new insights to support the development of novel diagnostic and/or therapeutic strategies for these diseases.

环状 RNA(circRNA)是一类新发现的非编码 RNA 转录本,因其在细胞信号传导中的调控作用而受到广泛关注。它们是共价闭合的非编码 RNA,形成一个环,通常在前体 RNA 的剪接过程中产生。循环 RNA 是基因表达程序的关键转录后和翻译后调控因子,可影响细胞反应和/或功能。特别是,circRNAs 被认为是特定 miRNA 的海绵,在转录后阶段调节细胞过程。越来越多的证据表明,circRNAs 的异常表达可能在多种疾病的发病机制中起到关键作用。值得注意的是,circRNAs、microRNAs 和几种 RNA 结合蛋白(包括抗增殖(APRO)家族蛋白)可能是不可或缺的基因调节剂,它们可能与疾病的发生密切相关。此外,circRNAs因其稳定性、在大脑中的丰度以及穿越血脑屏障的能力而受到普遍关注。在此,我们将介绍目前的研究结果以及 circRNA 在几种疾病中的治疗潜力。我们希望借此提供新的见解,以支持针对这些疾病的新型诊断和/或治疗策略的开发。
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引用次数: 0
The Role of Genetic Variants in the Long Non-Coding RNA Genes MALAT1 and H19 in the Pathogenesis of Childhood Obesity. 长链非编码RNA基因MALAT1和H19的遗传变异在儿童肥胖发病中的作用
IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-30 DOI: 10.3390/ncrna9020022
Tatiana Pavlovna Shkurat, Manar Ammar, Olga Bocharova, Elena Teplyakova, Anzhela Aleksandrova, Ruba Ali, Leonard Lipovich

Long non-coding RNAs (lncRNAs) play important roles in the maintenance of metabolic homeostasis. Recently, many studies have suggested that lncRNAs, such as Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and Imprinted Maternally Expressed Transcript (H19), might participate in the pathogenesis of metabolic disorders such as obesity. We conducted a case-control study with 150 Russian children and adolescents aged between 5 and 17 years old in order to assess the statistical association between the single nucleotide polymorphisms (SNPs) rs3200401 in MALAT1 and rs217727 in H19, and the risk of developing obesity in this population. We further explored the possible association of rs3200401 and rs217727 with BMI Z-score and insulin resistance. The MALAT1 rs3200401 and H19 rs217727 SNPs were genotyped using Taqman SNP genotyping assay. The MALAT1 rs3200401 SNP was identified as a risk factor for childhood obesity (p < 0.05) under the dominant and allelic models, and the CT heterozygous genotype was associated with the risk of increased BMI and with insulin resistance. The H19 rs217727 SNP had no significant association with obesity risk (all p > 0.05). Our findings thus suggest that MALAT1 SNP rs3200401 is a potential indicator of obesity susceptibility and pathogenesis in children and adolescents.

长链非编码rna (lncRNAs)在维持代谢稳态中起着重要作用。近年来,许多研究表明,转移相关肺腺癌转录本1 (MALAT1)和印迹母性表达转录本(H19)等lncrna可能参与了肥胖等代谢性疾病的发病机制。我们对150名年龄在5 - 17岁的俄罗斯儿童和青少年进行了一项病例对照研究,以评估MALAT1中rs3200401和H19中rs217727的单核苷酸多态性(snp)与该人群发生肥胖风险之间的统计学关联。我们进一步探讨rs3200401和rs217727与BMI Z-score和胰岛素抵抗的可能关联。采用Taqman SNP基因分型法对MALAT1 rs3200401和H19 rs217727 SNP进行基因分型。在显性和等位基因模型下,MALAT1 rs3200401 SNP被确定为儿童肥胖的危险因素(p 0.05), CT杂合基因型与BMI增加的风险和胰岛素抵抗相关。H19 rs217727 SNP与肥胖风险无显著相关性(均p > 0.05)。因此,我们的研究结果表明,MALAT1 SNP rs3200401是儿童和青少年肥胖易感性和发病机制的潜在指标。
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引用次数: 1
Therapeutic Effects of WT1 Silencing via Respiratory Administration of Neutral DOPC Liposomal-siRNA in a Lung Metastasis Melanoma Murine Model. 通过呼吸给药中性DOPC脂质体sirna沉默WT1对肺转移性黑色素瘤小鼠模型的治疗作用
IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-22 DOI: 10.3390/ncrna9020021
Martin R Ramos-Gonzalez, Eduardo Vazquez-Garza, Gerardo Garcia-Rivas, Cristian Rodriguez-Aguayo, Arturo Chavez-Reyes

The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 protein by siRNA in both in vitro in the B16F10 melanoma cell line and in vivo in a murine model of lung metastatic melanoma. We did this by implementing a novel respiratory delivery strategy of a neutral DOPC liposomal-siRNA system (L-siRNA). In vitro studies showed an effective silencing of the WT1 protein in the siRNAs' WT1-treated cells when compared with controls, resulting in a loss of the cell's viability and proliferation by inducing G1 arrest, the inhibition of the migration and invasion capacities of the cells, as well as the induction of apoptosis. In vivo, the respiratory administration of L-WT1 siRNA showed an efficient biodistribution on the lungs. After two weeks of treatment, the silencing of the WT1 protein resulted in an important antitumor activity that reduced the tumor weight. In the survival study, L-WT1 treatment could significantly delay the death of the animals. This work demonstrates the efficacy of the L-siRNA respiratory administration as a novel therapy to reduce pulmonary tumors and to increase survivability by silencing specific cancer oncogenes as WT1.

肺部是转移性黑色素瘤的常见靶点,因为它们为肿瘤的发展提供了高氧环境。WT1蛋白的过表达与黑色素瘤的发生有关。在这项研究中,我们评估了siRNA沉默WT1蛋白在体外对B16F10黑色素瘤细胞系和体内肺转移性黑色素瘤小鼠模型的影响。我们通过实施中性DOPC脂质体- sirna系统(L-siRNA)的新型呼吸递送策略来实现这一目标。体外研究表明,与对照组相比,sirna的WT1处理细胞中WT1蛋白的有效沉默,通过诱导G1阻滞,抑制细胞的迁移和侵袭能力,以及诱导细胞凋亡,导致细胞活力和增殖能力丧失。在体内,L-WT1 siRNA的呼吸给药在肺部表现出有效的生物分布。治疗两周后,WT1蛋白的沉默产生了重要的抗肿瘤活性,降低了肿瘤重量。在生存研究中,L-WT1治疗可显著延缓动物死亡。这项工作证明了L-siRNA呼吸给药作为一种新的治疗方法的有效性,通过沉默特定的癌症致癌基因如WT1来减少肺肿瘤和提高生存率。
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引用次数: 0
Reassessing the Abundance of miRNAs in the Human Pancreas and Rodent Cell Lines and Its Implication. 重新评估人类胰腺和啮齿动物细胞系中mirna的丰度及其意义。
IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-17 DOI: 10.3390/ncrna9020020
Guihua Sun, Meirigeng Qi, Alexis S Kim, Elizabeth M Lizhar, Olivia W Sun, Ismail H Al-Abdullah, Arthur D Riggs

miRNAs are critical for pancreas development and function. However, we found that there are discrepancies regarding pancreatic miRNA abundance in published datasets. To obtain a more relevant profile that is closer to the true profile, we profiled small RNAs from human islets cells, acini, and four rodent pancreatic cell lines routinely used in diabetes and pancreatic research using a bias reduction protocol for small RNA sequencing. In contrast to the previous notion that miR-375-3p is the most abundant pancreatic miRNA, we found that miR-148a-3p and miR-7-5p were also abundant in islets. In silico studies using predicted and validated targets of these three miRNAs revealed that they may work cooperatively in endocrine and exocrine cells. Our results also suggest, compared to the most-studied miR-375, that both miR-148a-3p and miR-7-5p may play more critical roles in the human pancreas. Moreover, according to in silico-predicted targets, we found that miR-375-3p had a much broader target spectrum by targeting the coding sequence and the 5' untranslated region, rather than the conventional 3' untranslated region, suggesting additional unexplored roles of miR-375-3p beyond the pancreas. Our study provides a valuable new resource for studying miRNAs in pancreata.

mirna对胰腺发育和功能至关重要。然而,我们发现在已发表的数据集中,胰腺miRNA丰度存在差异。为了获得更接近真实概况的更相关的概况,我们使用小RNA测序的偏倚减少方案,对糖尿病和胰腺研究中常规使用的人类胰岛细胞、腺泡细胞和四种啮齿动物胰腺细胞系的小RNA进行了分析。与之前认为miR-375-3p是最丰富的胰腺miRNA的观点相反,我们发现miR-148a-3p和miR-7-5p在胰岛中也很丰富。利用这三种mirna的预测和验证靶点进行的计算机研究表明,它们可能在内分泌和外分泌细胞中协同工作。我们的研究结果还表明,与研究最多的miR-375相比,miR-148a-3p和miR-7-5p可能在人类胰腺中发挥更关键的作用。此外,根据计算机预测的靶标,我们发现miR-375-3p具有更广泛的靶标谱,靶向编码序列和5'非翻译区,而不是传统的3'非翻译区,这表明miR-375-3p在胰腺之外还有其他未被探索的作用。本研究为胰腺mirna的研究提供了宝贵的新资源。
{"title":"Reassessing the Abundance of miRNAs in the Human Pancreas and Rodent Cell Lines and Its Implication.","authors":"Guihua Sun,&nbsp;Meirigeng Qi,&nbsp;Alexis S Kim,&nbsp;Elizabeth M Lizhar,&nbsp;Olivia W Sun,&nbsp;Ismail H Al-Abdullah,&nbsp;Arthur D Riggs","doi":"10.3390/ncrna9020020","DOIUrl":"https://doi.org/10.3390/ncrna9020020","url":null,"abstract":"<p><p>miRNAs are critical for pancreas development and function. However, we found that there are discrepancies regarding pancreatic miRNA abundance in published datasets. To obtain a more relevant profile that is closer to the true profile, we profiled small RNAs from human islets cells, acini, and four rodent pancreatic cell lines routinely used in diabetes and pancreatic research using a bias reduction protocol for small RNA sequencing. In contrast to the previous notion that miR-375-3p is the most abundant pancreatic miRNA, we found that miR-148a-3p and miR-7-5p were also abundant in islets. In silico studies using predicted and validated targets of these three miRNAs revealed that they may work cooperatively in endocrine and exocrine cells. Our results also suggest, compared to the most-studied miR-375, that both miR-148a-3p and miR-7-5p may play more critical roles in the human pancreas. Moreover, according to in silico-predicted targets, we found that miR-375-3p had a much broader target spectrum by targeting the coding sequence and the 5' untranslated region, rather than the conventional 3' untranslated region, suggesting additional unexplored roles of miR-375-3p beyond the pancreas. Our study provides a valuable new resource for studying miRNAs in pancreata.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9554274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long Noncoding RNA H19: A Novel Oncogene in Liver Cancer. 长非编码 RNA H19:肝癌中的新型癌基因
IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-09 DOI: 10.3390/ncrna9020019
Yanyan Wang, Jing Zeng, Weidong Chen, Jiangao Fan, Phillip B Hylemon, Huiping Zhou

Liver cancer is the second leading cause of cancer-related death globally, with limited treatment options. Recent studies have demonstrated the critical role of long noncoding RNAs (lncRNAs) in the pathogenesis of liver cancers. Of note, mounting evidence has shown that lncRNA H19, an endogenous noncoding single-stranded RNA, functions as an oncogene in the development and progression of liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the two most prevalent primary liver tumors in adults. H19 can affect many critical biological processes, including the cell proliferation, apoptosis, invasion, and metastasis of liver cancer by its function on epigenetic modification, H19/miR-675 axis, miRNAs sponge, drug resistance, and its regulation of downstream pathways. In this review, we will focus on the most relevant molecular mechanisms of action and regulation of H19 in the development and pathophysiology of HCC and CCA. This review aims to provide valuable perspectives and translational applications of H19 as a potential diagnostic marker and therapeutic target for liver cancer disease.

肝癌是全球癌症相关死亡的第二大原因,但治疗方法却很有限。最近的研究表明,长非编码 RNA(lncRNA)在肝癌的发病机制中起着至关重要的作用。值得注意的是,越来越多的证据表明,lncRNA H19 是一种内源性非编码单链 RNA,在肝癌(包括肝细胞癌(HCC)和胆管癌(CCA)这两种成人最常见的原发性肝肿瘤)的发生和发展过程中起着癌基因的作用。H19 可通过其表观遗传修饰、H19/miR-675 轴、miRNAs 海绵、耐药性及其对下游通路的调控等功能,影响许多关键的生物学过程,包括肝癌的细胞增殖、凋亡、侵袭和转移。在本综述中,我们将重点讨论 H19 在 HCC 和 CCA 的发展和病理生理学中最相关的分子作用和调控机制。本综述旨在为 H19 作为肝癌疾病的潜在诊断标志物和治疗靶点提供有价值的观点和转化应用。
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引用次数: 0
Insights into Online microRNA Bioinformatics Tools. 在线 microRNA 生物信息学工具透视。
IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-06 DOI: 10.3390/ncrna9020018
Diana Luna Buitrago, Ruth C Lovering, Andrea Caporali

MicroRNAs (miRNAs) are members of the small non-coding RNA family regulating gene expression at the post-transcriptional level. MiRNAs have been found to have critical roles in various biological and pathological processes. Research in this field has significantly progressed, with increased recognition of the importance of miRNA regulation. As a result of the vast data and information available regarding miRNAs, numerous online tools have emerged to address various biological questions related to their function and influence across essential cellular processes. This review includes a brief introduction to available resources for an investigation covering aspects such as miRNA sequences, target prediction/validation, miRNAs associated with disease, pathway analysis and genetic variants within miRNAs.

微RNA(miRNA)是在转录后水平调节基因表达的小型非编码RNA家族成员。人们发现,miRNA 在各种生物和病理过程中发挥着关键作用。随着人们越来越认识到 miRNA 调控的重要性,这一领域的研究取得了重大进展。由于有大量有关 miRNA 的数据和信息,出现了许多在线工具来解决与 miRNA 功能有关的各种生物学问题,以及它们对基本细胞过程的影响。本综述简要介绍了用于研究的可用资源,涵盖 miRNA 序列、目标预测/验证、与疾病相关的 miRNA、通路分析和 miRNA 中的遗传变异等方面。
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引用次数: 0
Immunoregulatory Biomarkers of the Remission Phase in Type 1 Diabetes: miR-30d-5p Modulates PD-1 Expression and Regulatory T Cell Expansion. 1型糖尿病缓解期的免疫调节生物标志物:miR-30d-5p调节PD-1表达和调节性T细胞扩增
IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-02-28 DOI: 10.3390/ncrna9020017
Laia Gomez-Muñoz, David Perna-Barrull, Marta Murillo, Maria Pilar Armengol, Marta Alcalde, Marti Catala, Silvia Rodriguez-Fernandez, Sergi Sunye, Aina Valls, Jacobo Perez, Raquel Corripio, Marta Vives-Pi

The partial remission (PR) phase of type 1 diabetes (T1D) is an underexplored period characterized by endogenous insulin production and downmodulated autoimmunity. To comprehend the mechanisms behind this transitory phase and develop precision medicine strategies, biomarker discovery and patient stratification are unmet needs. MicroRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression and modulate several biological processes, functioning as biomarkers for many diseases. Here, we identify and validate a unique miRNA signature during PR in pediatric patients with T1D by employing small RNA sequencing and RT-qPCR. These miRNAs were mainly related to the immune system, metabolism, stress, and apoptosis pathways. The implication in autoimmunity of the most dysregulated miRNA, miR-30d-5p, was evaluated in vivo in the non-obese diabetic mouse. MiR-30d-5p inhibition resulted in increased regulatory T cell percentages in the pancreatic lymph nodes together with a higher expression of CD200. In the spleen, a decrease in PD-1+ T lymphocytes and reduced PDCD1 expression were observed. Moreover, miR-30d-5p inhibition led to an increased islet leukocytic infiltrate and changes in both effector and memory T lymphocytes. In conclusion, the miRNA signature found during PR shows new putative biomarkers and highlights the immunomodulatory role of miR-30d-5p, elucidating the processes driving this phase.

1型糖尿病(T1D)的部分缓解期(PR)是一个未被充分探索的时期,其特征是内源性胰岛素产生和自身免疫下调。为了理解这一过渡阶段背后的机制并制定精准医疗策略,生物标志物的发现和患者分层是尚未满足的需求。MicroRNAs (miRNAs)是一种小的RNA分子,它负调控基因表达并调节多种生物过程,是许多疾病的生物标志物。在这里,我们通过小RNA测序和RT-qPCR鉴定并验证了儿科T1D患者PR期间独特的miRNA特征。这些mirna主要与免疫系统、代谢、应激和凋亡通路有关。在非肥胖糖尿病小鼠体内评估了最失调的miRNA miR-30d-5p对自身免疫的影响。MiR-30d-5p抑制导致胰腺淋巴结中调节性T细胞百分比增加,同时CD200表达增加。脾脏中PD-1+ T淋巴细胞减少,PDCD1表达降低。此外,miR-30d-5p抑制导致胰岛白细胞浸润增加,效应T淋巴细胞和记忆T淋巴细胞发生变化。总之,在PR过程中发现的miRNA特征显示了新的假定的生物标志物,并突出了miR-30d-5p的免疫调节作用,阐明了驱动这一阶段的过程。
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引用次数: 1
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Non-Coding RNA
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