Non-coding RNA Research最新文献_第6页

LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injury LncRNA MIR155HG在脊髓损伤中通过miR-7036b-3p/GPNMB轴和AMPK/mTOR信号通路激活自噬，从而抑制细胞凋亡

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-22 DOI: 10.1016/j.ncrna.2025.05.013

Ruoxi Liu , Jintao Ye , Sihua Huang

Background

Long non-coding RNAs (lncRNAs) participate in spinal cord injury (SCI) development through regulating autophagy and neuronal apoptosis. Previously, MIR155HG was identified as an upregulated lncRNA in rat bladder tissues harvested after SCI operation. Our study aimed to elucidate the function of MIR155HG in SCI.

Methods

Glutamate (Glu)-stimulated primary mouse spinal cord neurons were used as SCI cellular models. Contusion-induced SCI mouse models were established using an improved weightlessness method. Neuronal apoptosis and autophagy affected by MIR155HG or GPNMB silencing were assessed by TUNEL staining, flow cytometry assay, western blotting, and immunofluorescence staining. The binding of miR-7036b-3p on MIR155HG (or GPNMB) was verified by luciferase reporter assay. Histological changes were observed through HE and Masson staining.

Results

MIR155HG and GPNMB expression was elevated while miR-7036b-3p expression was reduced in SCI. MIR155HG silencing attenuated the apoptosis in Glu-stimulated neurons and ameliorated glial scar formation and motor function of SCI mice. GPNMB knockdown mitigated apoptosis, enhanced autophagy, activated AMPK phosphorylation, and repressed mTOR phosphorylation. MIR155HG upregulated GPNMB expression by sponging miR-7036b-3p. The autophagy inhibitor 3-MA reversed the above changes caused by GPNMB depletion.

Conclusion

MIR155HG knockdown alleviated neuronal apoptosis by enhancing autophagy in SCI via miR-7036b-3p/GPNMB axis and AMPK/mTOR pathway.

长链非编码rna （lncRNAs）通过调控自噬和神经元凋亡参与脊髓损伤（SCI）的发生发展。先前，MIR155HG被鉴定为SCI手术后收获的大鼠膀胱组织中上调的lncRNA。我们的研究旨在阐明MIR155HG在脊髓损伤中的作用。方法采用谷氨酸（Glu）刺激小鼠原代脊髓神经元作为脊髓损伤细胞模型。采用改进失重法建立挫伤性脊髓损伤小鼠模型。通过TUNEL染色、流式细胞术、western blotting和免疫荧光染色观察MIR155HG或GPNMB沉默对神经元凋亡和自噬的影响。通过荧光素酶报告基因实验验证miR-7036b-3p与MIR155HG（或GPNMB）的结合。HE染色、Masson染色观察组织学改变。结果脊髓损伤组smir155hg、GPNMB表达升高，miR-7036b-3p表达降低。MIR155HG沉默可减轻脊髓损伤小鼠胶质刺激神经元的凋亡，改善神经胶质瘢痕形成和运动功能。GPNMB敲低可减轻细胞凋亡，增强自噬，激活AMPK磷酸化，抑制mTOR磷酸化。MIR155HG通过海绵转染miR-7036b-3p上调GPNMB的表达。自噬抑制剂3-MA逆转了GPNMB耗竭引起的上述变化。结论mir155hg下调可通过miR-7036b-3p/GPNMB轴和AMPK/mTOR通路增强脊髓损伤后神经元的自噬从而减轻神经元凋亡。

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引用次数: 0

MiR-92a-1-5p contributes to cellular proliferation and survival in chronic myeloid leukemia and its inhibition enhances imatinib efficacy MiR-92a-1-5p参与慢性髓性白血病细胞增殖和存活，抑制MiR-92a-1-5p可增强伊马替尼的疗效

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-21 DOI: 10.1016/j.ncrna.2025.05.008

Joanne Peters , Emeline Bollaert , Anne-Sophie Cloos , Melissa Claus , Ahmed Essaghir , Sandrine Lenglez , Pascale Saussoy , Guillaume Dachy , Pierre Autin , Jean-Baptiste Demoulin , Violaine Havelange

Tyrosine kinase inhibitors (TKI), such as imatinib, have revolutionized chronic myeloid leukemia (CML) treatment. Despite this success, TKI intolerance and resistance remain significant clinical challenges. A promising therapeutic approach is to simultaneously target the BCR::ABL1 oncogene and other oncogenic drivers. The polycistronic miR-17-92 cluster is known to contribute to CML development and progression, but the specific roles of miR-92a-1-5p within this cluster remain unclear. In this study, we assess the roles of this microRNA and evaluate the therapeutic potential of combining microRNA inhibition with imatinib to improve treatment outcome. Our results show that miR-92a-1-5p is downregulated by imatinib in myeloid cell lines harboring BCR::ABL1 and in CML patient samples. Inhibition of miR-92a-1-5p reduces proliferation and enhances imatinib-induced cell death, while its overexpression increases proliferation and counteracts the effects of imatinib on cell death. This decrease in proliferation caused by miR-92a-1-5p inhibition is rescued after simultaneous inhibition of two newly identified target genes: BNIP3L (NIX) and TP53INP1. We confirm that miR-92a-1-5p regulates proliferation and cell cycle by targeting TP53INP1 and decreases autophagy by targeting BNIP3L. Our data suggest that miR-92a-1-5p plays a role in CML progression, and its inhibition enhances imatinib anti-leukemic efficacy, making it a potential therapeutic target.

酪氨酸激酶抑制剂（TKI），如伊马替尼，已经彻底改变了慢性髓性白血病（CML）的治疗。尽管取得了这一成功，TKI不耐受和耐药仍然是重大的临床挑战。一种有希望的治疗方法是同时靶向BCR::ABL1癌基因和其他致癌驱动因子。已知多顺反性miR-17-92簇有助于CML的发生和进展，但miR-92a-1-5p在该簇中的具体作用尚不清楚。在本研究中，我们评估了这种microRNA的作用，并评估了将microRNA抑制与伊马替尼联合使用以改善治疗结果的治疗潜力。我们的研究结果表明，在BCR::ABL1的髓系和CML患者样本中，miR-92a-1-5p被伊马替尼下调。抑制miR-92a-1-5p可减少增殖并增强伊马替尼诱导的细胞死亡，而其过表达可增加增殖并抵消伊马替尼对细胞死亡的影响。抑制miR-92a-1-5p导致的增殖减少在同时抑制两个新发现的靶基因：BNIP3L （NIX）和TP53INP1后得到挽救。我们证实miR-92a-1-5p通过靶向TP53INP1调节增殖和细胞周期，并通过靶向BNIP3L减少自噬。我们的数据表明，miR-92a-1-5p在CML进展中发挥作用，其抑制作用增强了伊马替尼抗白血病的疗效，使其成为潜在的治疗靶点。

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引用次数: 0

Computational discovery of conserved RNA structures and functional characterization of a structured lncRNA in Leishmania braziliensis 巴西利什曼原虫保守RNA结构的计算发现和结构lncRNA的功能表征

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-20 DOI: 10.1016/j.ncrna.2025.05.010

Caroline R. Espada , Christian Anthon , Rubens D.M. Magalhães , José Carlos Quilles Junior , Natalia M.M. Teles , Fabiano S. Pais , Lissur A. Orsine , Letícia de Almeida , Tânia P.A. Defina , Adam Dowle , Jan Gorodkin , Pegine B. Walrad , Angela K. Cruz

Leishmania parasites alternate between hosts, facing environmental changes that demand rapid gene expression adaptation. Lacking canonical RNA polymerase II promoters, transcription in these eukaryotes is polycistronic, with gene regulation occurring post-transcriptionally. Although non-coding RNAs (ncRNAs) have been identified in Leishmania transcriptomes, their functions remain unclear. Recognizing RNA structure's importance, we performed a genome-wide alignment of L. braziliensis and related species, identifying conserved RNA structures, 38 of which overlap with known ncRNAs. One such ncRNA, lncRNA45, was functionally characterized. Using a knockout cell line, we demonstrated that lncRNA45 is crucial for parasite fitness. Reintroducing the wild type lncRNA45 restored fitness, while a version with a single nucleotide substitution in the structured region did not. This mutation also altered RNA-protein interactions. These findings suggest that lncRNA45's regulatory role and protein interactions rely on its secondary structure. This study highlights the significance of structured lncRNAs in Leishmania biology and their potential as therapeutic targets. Further research into these ncRNAs could uncover new parasite regulation mechanisms and inspire novel treatment strategies.

利什曼原虫在宿主之间交替，面临需要快速基因表达适应的环境变化。缺乏典型的RNA聚合酶II启动子，这些真核生物的转录是多顺反子的，基因调控发生在转录后。虽然在利什曼原虫转录组中发现了非编码rna (ncRNAs)，但其功能尚不清楚。认识到RNA结构的重要性，我们对巴西乳杆菌和相关物种进行了全基因组比对，鉴定出保守的RNA结构，其中38个与已知的ncRNAs重叠。其中一个ncRNA lncRNA45已被功能表征。通过敲除细胞系，我们证明了lncRNA45对寄生虫适应性至关重要。重新引入野生型lncRNA45恢复了适应度，而在结构区域进行单核苷酸替换的版本则没有。这种突变也改变了rna -蛋白质的相互作用。这些发现表明lncRNA45的调控作用和蛋白质相互作用依赖于其二级结构。本研究强调了结构lncrna在利什曼原虫生物学中的重要性及其作为治疗靶点的潜力。对这些ncrna的进一步研究可能会发现新的寄生虫调控机制，并激发新的治疗策略。

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引用次数: 0

Exosome-derived hsa_circ_0007132 promotes lenvatinib resistance by inhibiting the ubiquitin-mediated degradation of NONO 外泌体衍生的hsa_circ_0007132通过抑制泛素介导的NONO降解来促进lenvatinib耐药性

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-15 DOI: 10.1016/j.ncrna.2025.05.007

Mingbo Cao , Yuxuan Li , Xiaorui Su , Yongchang Tang , Feng Yuan , Yupeng Ren , Meihai Deng , Zhicheng Yao

Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor, with its incidence showing a troubling upward trend over the past decade. Lenvatinib is one of the first-line medications for treating advanced HCC, however, the development of resistance significantly undermines its potential to improve patient prognosis. In recent years, exosomal circRNAs have been implicated in the resistance mechanisms of various cancers, yet their role in mediating lenvatinib resistance (LR) remains largely unexplored. In this study, we identified hsa_circ_0007132, which is upregulated in the serum exosomes of HCC patients exhibiting progressive disease (PD) following lenvatinib treatment. Subsequently, we employed LR cell lines to conduct both in vitro and in vivo experiments, which provided compelling evidence that hsa_circ_0007132 significantly promotes LR in HCC. Mechanistically, hsa_circ_0007132 interacts with the NONO protein, impairing its ubiquitination and leading to increased stability and upregulation of NONO expression, thereby enhancing NONO-mediated nuclear export of ZEB1 mRNA and elevating ZEB1 protein expression, which ultimately contributes to LR. In summary, our findings unveil a critical mechanism through which HCC mediates tumor progression and LR via exosomal hsa_circ_0007132, while also emphasizing that targeting NONO may represent a promising therapeutic strategy to overcome LR.

肝细胞癌（HCC）是一种高度异质性的实体肿瘤，其发病率在过去十年中呈现出令人不安的上升趋势。Lenvatinib是治疗晚期HCC的一线药物之一，然而耐药的发展显著削弱了其改善患者预后的潜力。近年来，外泌体环状rna与各种癌症的耐药机制有关，但它们在介导lenvatinib耐药（LR）中的作用仍未被广泛探索。在这项研究中，我们发现hsa_circ_0007132在lenvatinib治疗后出现进展性疾病（PD）的HCC患者的血清外泌体中表达上调。随后，我们利用LR细胞系进行了体外和体内实验，提供了令人信服的证据，证明hsa_circ_0007132在HCC中显著促进LR。从机制上讲，hsa_circ_0007132与NONO蛋白相互作用，损害其泛素化，导致NONO表达的稳定性增强和上调，从而增强NONO介导的ZEB1 mRNA的核输出，提高ZEB1蛋白的表达，最终导致LR。总之，我们的研究结果揭示了HCC通过外泌体hsa_circ_0007132介导肿瘤进展和LR的关键机制，同时也强调靶向NONO可能是克服LR的一种有希望的治疗策略。

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引用次数: 0

Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis Ocrelizumab在多发性硬化症中调节基因和microRNA表达的作用

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-15 DOI: 10.1016/j.ncrna.2025.05.009

Bruna De Felice , Elisabetta Signoriello , Concetta Montanino , Giuseppe Romano , Deborah Archetto , Elisabetta Maida , Martina Marciano , Simona Bonavita , Giacomo Lus , Federica Farinella , Cinzia Coppola

Multiple sclerosis is an autoimmune neurodegenerative disease and one of the most significant challenges in modern neurology, impacting approximately 2.8 million people globally. As a multifactorial condition, susceptibility to MS can result from a combination of genetic and environmental factors. Current treatment strategies aim to prevent acute attacks, slow disease progression, and alleviate symptoms. Ocrelizumab, a monoclonal antibody targeting CD20, has demonstrated efficacy in clinical trials by reducing both disease activity and frequency of relapses.

Given the recent approval of this treatment, we investigated whether Ocrelizumab alters the expression of key miRNAs and genes involved in neuroinflammation, such as let-7a-5p, miR-14a-5p, miR-21a-5p, miR-338-3p, IL-1, IL-6, NEAT1, NEFL, NESTIN, SLC16A10 and TNF-alpha, by comparing their expression in patients’ blood before and after one year of treatment with Ocrelizumab. Additionally, we explored potential inverse correlations and direct or indirect interactions among the genes and miRNAs that showed significant changes in expression. Lastly, we conducted a pathway analysis to understand the overall effects potentially exerted by the drug.

Results revealed a significant decrease in the expression of TNF-alpha, SLC16A10, NEFL and IL-6, and an increase in let-7a-5p expression. There was an inverse correlation between let-7a-5p and the four genes, while the genes positively correlated with each other, suggesting let-7a-5p as a common modulator. These findings indicate that further investigation is needed to determine if the drug directly upregulates let-7a-5p, thereby downregulating the four genes, or if these expression changes are an indication of an overall reduction in inflammation.

多发性硬化症是一种自身免疫性神经退行性疾病，也是现代神经病学中最重大的挑战之一，影响着全球约280万人。作为一种多因素疾病，多发性硬化症的易感性可能是遗传和环境因素共同作用的结果。目前的治疗策略旨在预防急性发作，减缓疾病进展，减轻症状。Ocrelizumab是一种靶向CD20的单克隆抗体，通过降低疾病活动性和复发频率在临床试验中证明了疗效。鉴于该疗法最近获得批准，我们研究了Ocrelizumab是否会改变与神经炎症相关的关键mirna和基因的表达，如let-7a-5p、miR-14a-5p、miR-21a-5p、miR-338-3p、IL-1、IL-6、NEAT1、NEFL、NESTIN、SLC16A10和tnf - α，通过比较它们在Ocrelizumab治疗前后患者血液中的表达。此外，我们探索了基因和mirna之间潜在的负相关和直接或间接的相互作用，这些基因和mirna显示出显著的表达变化。最后，我们进行了途径分析，以了解该药物可能发挥的总体作用。结果显示，tnf - α、SLC16A10、NEFL和IL-6的表达显著降低，let-7a-5p的表达显著升高。let-7a-5p与这四个基因呈负相关，而基因之间呈正相关，说明let-7a-5p是一个共同的调节因子。这些发现表明，需要进一步的研究来确定该药物是否直接上调了let-7a-5p，从而下调了这四个基因，或者这些表达变化是否表明炎症的总体减少。

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引用次数: 0

Tongue squamous cell carcinoma-derived exosomes miR-21-5p affect tumor progression via promoting M2 macrophage polarization 舌鳞癌源性外泌体miR-21-5p通过促进M2巨噬细胞极化影响肿瘤进展

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-15 DOI: 10.1016/j.ncrna.2025.05.006

Zixian Xu , Xin Fang , Shan Wang , Jiabei Mu , Qixian Gai , Yantong Chen , Zheyi Sun , Jiemei Zhai

Exosome-mediated intercellular communication plays a key role in shaping the tumor microenvironment and promoting tumor progression. Recent studies have demonstrated that tumor exosomal miRNAs significantly contribute to the polarization of tumor-associated macrophages (TAMs). However, the molecular mechanisms underlying miRNA-mediated regulation of macrophage polarization by exosomes derived from tongue squamous cell carcinoma (TSCC) remain incompletely elucidated. In this study, small RNA sequencing analysis of exosomal miRNAs revealed miR-21-5p was highly expressed in TSCC-derived exosomes. Further investigation demonstrated a significant association between exosomal miR-21-5p and M2 polarization of tumor-associated macrophages (TAMs). Functionally, TSCC-derived exosomes promoted the polarization of M0 macrophages towards the M2 phenotype. Mechanistically, exosomal miR-21-5p enhanced M2 polarization of TAMs by inhibiting phosphorylation of ERK1/2. Additionally, we performed single-sample gene set enrichment analysis (ssGSEA), constructed a multivariate Cox regression model, and performed survival analysis using paired RNA transcriptome and clinical data from TSCC patients. Our results revealed a significant enrichment of M2 macrophages in the tumor microenvironment (TME) of TSCC compared to adjacent normal tissue. Furthermore, we confirmed that M2 macrophages infiltration is associated with poor prognosis in TSCC patients. In summary, our study demonstrates that TSCC-derived exosomal miR-21-5p plays an critical role in M2 macrophage polarization, and M2 macrophages infiltration contributes to the progression of TSCC. Therefore, these findings suggest that therapeutic targeting of miR-21-5p may represent a novel strategy for TSCC treatment by selectively modulating the M2 polarization of TAMs.

外泌体介导的细胞间通讯在塑造肿瘤微环境和促进肿瘤进展中起着关键作用。最近的研究表明，肿瘤外泌体mirna显著促进肿瘤相关巨噬细胞（tam）的极化。然而，来自舌鳞状细胞癌（TSCC）的外泌体通过mirna介导巨噬细胞极化调节的分子机制尚未完全阐明。在这项研究中，外泌体miRNAs的小RNA测序分析显示，miR-21-5p在tscc衍生的外泌体中高度表达。进一步的研究表明，外泌体miR-21-5p与肿瘤相关巨噬细胞（tam）的M2极化之间存在显著关联。功能上，tscc衍生的外泌体促进M0巨噬细胞向M2表型极化。机制上，外泌体miR-21-5p通过抑制ERK1/2的磷酸化来增强tam的M2极化。此外，我们进行了单样本基因集富集分析（ssGSEA），构建了多变量Cox回归模型，并使用配对RNA转录组和TSCC患者的临床数据进行了生存分析。我们的研究结果显示，与邻近正常组织相比，TSCC肿瘤微环境（TME）中M2巨噬细胞显著富集。此外，我们证实M2巨噬细胞浸润与TSCC患者预后不良有关。综上所述，我们的研究表明，TSCC来源的外泌体miR-21-5p在M2巨噬细胞极化中起关键作用，M2巨噬细胞浸润有助于TSCC的进展。因此，这些发现表明，靶向治疗miR-21-5p可能是一种通过选择性调节tam的M2极化来治疗TSCC的新策略。

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引用次数: 0

Characterization of small nucleolar RNA retaining transcripts in human normal and cancer cells 人类正常细胞和癌细胞中小核仁RNA保留转录物的表征

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-09 DOI: 10.1016/j.ncrna.2025.05.004

Guglielmo Rambaldelli , Sidra Asghar , Giulia Venturi , Federico Zacchini , Margherita Serra , Catia Giovannini , Laura Gramantieri , Marco Bernini , Alberto Inga , Erik Dassi , Lorenzo Montanaro

Small nucleolar RNAs are non-coding RNAs typically encoded within the introns of both protein-coding and non-coding genes. Interestingly, a significant fraction of snoRNA sequences is found as retained introns of specific mRNA isoforms expressed from their host gene. In the present study, we aimed to define the representation of small nucleolar RNA retaining transcripts across various human cell types and tissues including cancer. We found that these type of transcripts are widely represented in normal tissues and cancer-derived cell lines, appearing both in their full-length form and, frequently, in a shorter variant. We characterized the shortening position, which occurs at or very close to the retained small nucleolar RNA sequence at the 5′ end. Interestingly, for some transcripts this shorter variant represents the only form detected. In addition, some of the small nucleolar RNA retaining transcripts can be localized into the cellular cytoplasmic fraction. Moreover, our findings point out that a variable but consistent proportion of small nucleolar RNA sequences in cells, tissues, and liquid biopsy samples is, in fact, present as small nucleolar RNA retaining transcripts, indicating that these elements should be carefully considered when snoRNA are evaluated as biomarkers. Considering that short reads and gene-based transcriptomic analysis completely overlooked these transcripts, potentially missing critical insights into their involvement in cancer and other diseases, our results strongly indicate that these type of transcripts should be further investigated in different contexts to better understand their biogenesis, sequence features, presence, and role within cells.

小核仁rna是非编码rna，通常编码于蛋白质编码基因和非编码基因的内含子内。有趣的是，相当一部分的snoRNA序列被发现为宿主基因表达的特定mRNA同种异构体的保留内含子。在本研究中，我们旨在确定小核仁RNA保留转录物在各种人类细胞类型和组织（包括癌症）中的代表性。我们发现这些类型的转录本在正常组织和癌症来源的细胞系中广泛存在，既以全长形式出现，也经常以较短的变体出现。我们描述了缩短位置，它发生在或非常接近保留的小核仁RNA序列在5 '端。有趣的是，对于某些转录本，这种较短的变体代表了检测到的唯一形式。此外，一些小的核仁RNA保留转录本可以定位到细胞质部分。此外，我们的研究结果指出，在细胞、组织和液体活检样本中，小核仁RNA序列的可变但一致的比例实际上是作为保留小核仁RNA的转录本存在的，这表明在将snoRNA作为生物标志物进行评估时，应仔细考虑这些元素。考虑到短读和基于基因的转录组学分析完全忽略了这些转录本，可能错过了它们参与癌症和其他疾病的关键见解，我们的结果强烈表明，这些类型的转录本应该在不同的背景下进一步研究，以更好地了解它们的生物发生、序列特征、存在和在细胞中的作用。

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引用次数: 0

Maternal plasma microRNAs as potential biomarkers for triaging pregnancies of unknown location and ectopic pregnancy diagnosis 孕妇血浆microrna作为未知部位妊娠分类和异位妊娠诊断的潜在生物标志物

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-08 DOI: 10.1016/j.ncrna.2025.05.005

Christopher Kyriacou , Sung Hye Kim , Maria Arianoglou , Shabnam Bobdiwala , Margaret Pikovsky , Nina Parker , Jennifer Barcroft , Maya Al-Memar , Phillip R. Bennett , David A. MacIntyre , Tom Bourne , Vasso Terzidou

Background

Pregnancy of unknown location (PUL) is classified if an early pregnancy is not visualised on transvaginal ultrasonography (TVUS). Biomarkers currently used to triage PUL outcomes have varying accuracy. Delayed or missed diagnosis of ectopic pregnancies (EP) continue to cause significant morbidity and mortality. We investigated whether maternal plasma microRNAs (miRNAs) can predict and differentiate high-risk EP from viable (VIUP) or non-viable (NVIUP) intrauterine pregnancies.

Methods

Plasma was collected from women with PUL/EP (n = 120), mostly between four to eight weeks’ gestation, where outcomes of EP (n = 39), VIUP (n = 58) and NVIUP (miscarriage, n = 23) were determined using TVUS. Nanostring nCounter miRNA assay was used to examine the expression of ∼800 miRNAs in 22 women. Differentially expressed miRNAs were validated using RT-qPCR in 98 women.

Results

Nanostring nCounter miRNA assay identified 19 miRNAs which were expressed significantly higher in EP/NVIUP compared with VIUP. Two miRNAs were validated in a second, separate validation cohort using RT-qPCR: hsa-miR-21-5p in EP was 2.8-fold higher than in VIUP (p = 0.03, ROC AUC = 0.64), and hsa-miR-411-5p had 0.2-fold decreased expression (p = 0.02, ROC AUC = 0.66). Combining the divergent miRNAs as a ratio improved discrimination of EP from VIUP (p < 0.001, ROC AUC = 0.74).

Conclusion

Plasma miRNAs are differentially expressed in EP and VIUP and are detectable as early as four gestational weeks. Exploring miRNA targets may further understanding of EP pathophysiology, offering the potential to use miRNA as predictive and diagnostic markers in early pregnancy.

背景：如果早期妊娠未在阴道超声检查（TVUS）上显像，则应分类为不明位置妊娠（PUL）。目前用于诊断PUL结果的生物标志物具有不同的准确性。延迟或漏诊的异位妊娠（EP）继续导致显著的发病率和死亡率。我们研究了母体血浆microRNAs （miRNAs）是否可以预测和区分高危EP与活胎（VIUP）或非活胎（NVIUP）宫内妊娠。方法收集PUL/EP患者（n = 120）的血浆，大多数为妊娠4 ~ 8周，其中EP (n = 39), VIUP （n = 58）和NVIUP（流产，n = 23）的结局使用TVUS进行测定。使用Nanostring nCounter miRNA检测22名女性中~ 800种miRNA的表达。在98名女性中使用RT-qPCR验证了差异表达的mirna。结果snanostring nCounter miRNA检测鉴定出EP/NVIUP中表达量显著高于VIUP的19个miRNA。使用RT-qPCR在第二个单独的验证队列中验证了两个mirna: hsa-miR-21-5p在EP中比VIUP高2.8倍（p = 0.03, ROC AUC = 0.64）， hsa-miR-411-5p表达降低0.2倍（p = 0.02, ROC AUC = 0.66）。将不同的mirna按比例组合可以提高EP与VIUP的区别(p <；0.001, roc auc = 0.74)。结论血浆mirna在EP和VIUP中存在差异表达，早在妊娠4周就可检测到。探索miRNA靶点可以进一步了解EP的病理生理，为使用miRNA作为早期妊娠的预测和诊断标志物提供了潜力。

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引用次数: 0

Circ_0054633 silencing suppresses hyperglycemia-induced extracellular matrix accumulation in renal mesangial cells by regulating MiR-136-5p/SMAD3 signaling Circ_0054633沉默通过调节MiR-136-5p/SMAD3信号传导抑制高血糖诱导的肾系膜细胞细胞外基质积累

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-06 DOI: 10.1016/j.ncrna.2025.05.003

Qing Jiang , Hongxin Chen , Ke Wang , Xiaowei Zhu , Jun Yin , Wei Tang

Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM), with excessive deposition of the extracellular matrix (ECM) produced by glomerular mesangial cells being its critical hallmark. circ_0054633, a circular RNA, is a promising biomarker for DM; however, the role of this circular RNA in DKD remains unknown. This study enrolled 10 healthy controls (CT), 10 DM patients, and 10 DKD patients, and serum circ_0054633 expression was analyzed. Circ_0054633 levels gradually increased in the CT, DM, and DKD groups, which also correlated with the serum indicator albumin/urine creatinine ratio and the degree of fibrosis. In vitro experiments, circ_0054633 silencing markedly attenuated hyperglycemia stress-induced cell proliferation and ECM accumulation in human renal mesangial cells). In vivo experiments indicated that circ_0054633 silencing in the db/db mouse kidney suppressed renal fibrosis. Mechanistically, circ_0054633 silencing exerted its effect by releasing miR-136-5p, which then downregulated SMAD3. The present study possibly demonstrates the clinical significance of circ_0054633, which may be a target for future DKD treatment.

糖尿病肾病（DKD）是糖尿病（DM）最常见的并发症，肾小球系膜细胞产生的细胞外基质（ECM）过度沉积是其重要标志。环状RNA circ_0054633是一种很有前景的糖尿病生物标志物；然而，这种环状RNA在DKD中的作用尚不清楚。本研究招募了10名健康对照（CT）、10名糖尿病患者和10名DKD患者，分析了血清circ_0054633的表达。Circ_0054633水平在CT、DM、DKD组逐渐升高，且与血清白蛋白/尿肌酐比值及纤维化程度相关。体外实验表明，circ_0054633沉默可显著降低高血糖应激诱导的细胞增殖和人肾系膜细胞ECM积累。体内实验表明circ_0054633在db/db小鼠肾中沉默可抑制肾纤维化。机制上，circ_0054633沉默通过释放miR-136-5p发挥作用，miR-136-5p随后下调SMAD3。本研究可能证明circ_0054633的临床意义，它可能是未来DKD治疗的靶点。

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引用次数: 0

The emerging role of miRNAs in biological aging and age-related diseases mirna在生物衰老和年龄相关疾病中的新作用

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-05 DOI: 10.1016/j.ncrna.2025.05.002

Rawad Turko , Amro Hajja , Ahmad M. Magableh , Mohammed H. Omer , Areez Shafqat , Mohammad Imran Khan , Ahmed Yaqinuddin

Ageing is a complex biological process characterised by the accumulation of molecular and cellular damage leading to functional decline and an increased risk of chronic disease and geriatric syndromes. Despite data showing that lifestyle modifications, such as caloric restriction and exercise, can lead to healthy ageing and greatly reduce the incidence of chronic disorders, no medical therapies exist to delay or prevent these conditions effectively. We also lack tools to effectively track the ageing process in a manner that predicts an individual's risk of chronic disease and assess response to lifestyle or medical interventions. This review explores the emerging role of microRNAs (miRNAs), which are small non-coding RNAs that regulate gene expression, as a unifying mechanism underlying the biology of ageing and age-related conditions, including cardiovascular and neurodegenerative diseases, metabolic syndromes, musculoskeletal disorders such as sarcopenia, osteoarthritis and osteoporosis, and various cancers. We also examine the interactions of miRNAs with various hallmarks of ageing, such as DNA damage, cellular senescence, and mitochondrial dysfunction. We then explore the challenges of translating miRNA-based approaches from preclinical promise to clinical utility, emphasizing the need for trial-level validation to correlate miRNA profiles with clinically meaningful, patient-centred endpoints. By consolidating these findings, this article puts miRNAs forward as a pivotal mechanism in geroscience, offering a novel framework to mitigate ageing-related multimorbidity and bridge the gap between lifespan and healthspan.

衰老是一个复杂的生物过程，其特点是分子和细胞损伤的积累导致功能下降，慢性病和老年综合症的风险增加。尽管数据显示，改变生活方式，如限制热量摄入和锻炼，可导致健康老龄化，并大大减少慢性疾病的发病率，但目前尚无有效延缓或预防这些疾病的医疗疗法。我们还缺乏有效跟踪衰老过程的工具，无法预测个人患慢性病的风险，也无法评估对生活方式或医疗干预的反应。这篇综述探讨了microRNAs （miRNAs）的新作用，这是一种调节基因表达的小非编码rna，作为衰老和年龄相关疾病生物学的统一机制，包括心血管和神经退行性疾病，代谢综合征，肌肉骨骼疾病，如肌肉减少症，骨关节炎和骨质疏松症，以及各种癌症。我们还研究了mirna与各种衰老特征的相互作用，如DNA损伤、细胞衰老和线粒体功能障碍。然后，我们探讨了将基于miRNA的方法从临床前应用转化为临床应用的挑战，强调需要进行试验水平的验证，以将miRNA谱与临床有意义的、以患者为中心的终点相关联。通过巩固这些发现，本文提出了miRNAs在老年科学中的关键机制，为减轻衰老相关的多病和弥合寿命与健康寿命之间的差距提供了一个新的框架。

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引用次数: 0