Non-coding RNA Research最新文献_第8页

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 : 2025-08-01 Epub 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

HNRNPC stabilizes m6A-modified AC145207.5 to accelerate tumorigenesis in colorectal cancer by impeding the Nrf2/GPX4 axis-mediated ferroptosis HNRNPC稳定m6a修饰的AC145207.5，通过阻止Nrf2/GPX4轴介导的铁凋亡来加速结直肠癌的肿瘤发生

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-08-01 Epub Date: 2025-04-07 DOI: 10.1016/j.ncrna.2025.04.002

Dan Liu , Shanshan Lin , Yueben Hu , Jianyong Xiong , Hongtao Wan , Yanglin Chen , Taohui Ding , Hu Zhao , Renjie Jiang , Zhijiang Huang , Dengke Yao , Ming Li , Xiaojian Zhu , Bo Yi

Ferroptosis is an apoptosis-independent cell death pathway characterized by heightened lipid peroxidation, which shows promise for tumor suppression. Despite extensive research on long non-coding RNAs (LncRNAs) in ferroptosis, their role in colorectal cancer (CRC) remains underexplored. We investigated the upregulation of AC145207.5 and HNRNPC expression in CRC tissues through public dataset analysis and in-house validation, identifying them as having significant diagnostic potential. In vitro experiments including MTS assay, transwell, and colony formation, alongside in vivo studies using xenograft models, elucidated the synergistic carcinogenic role of the HNRNPC/AC145207.5 axis in promoting the malignant characteristics of CRC. Mechanistically, the m6A reader HNRNPC stabilized m6A-modified AC145207.5, contributing to its stabilization and upregulation. Consequently, AC145207.5 activated the Nrf2/GPX4 axis, resulting in increased GPX4 expression, inhibition of GPX4-mediated ferroptosis, and facilitation of CRC progression. Our findings underscore the clinical relevance of the HNRNPC/AC145207.5 axis in CRC and illuminate its regulatory role in ferroptosis, suggesting implications for targeted precision medicine in CRC.

铁凋亡是一种不依赖于细胞凋亡的细胞死亡途径，其特征是脂质过氧化升高，具有抑制肿瘤的前景。尽管对长链非编码rna （LncRNAs）在铁下垂中的作用进行了广泛的研究，但它们在结直肠癌（CRC）中的作用仍未得到充分探讨。我们通过公共数据集分析和内部验证研究了AC145207.5和HNRNPC在结直肠癌组织中的表达上调，确定它们具有重要的诊断潜力。体外实验包括MTS测定、transwell和集落形成，以及使用异种移植模型的体内研究，阐明了HNRNPC/AC145207.5轴在促进CRC恶性特征中的协同致癌作用。从机制上说，m6A读取器HNRNPC稳定了m6A修饰的AC145207.5，有助于其稳定和上调。因此，AC145207.5激活Nrf2/GPX4轴，导致GPX4表达增加，抑制GPX4介导的铁下垂，促进CRC进展。我们的研究结果强调了HNRNPC/AC145207.5轴在结直肠癌中的临床相关性，并阐明了其在铁下垂中的调节作用，为结直肠癌的靶向精准医学提供了指导。

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引用次数: 0

LINC02679 regulates TRIML2 to promote gastric cancer proliferation and invasion via targeting miR-5004-3p LINC02679 通过靶向 miR-5004-3p 调节 TRIML2，促进胃癌的增殖和侵袭

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-08-01 Epub Date: 2025-04-01 DOI: 10.1016/j.ncrna.2025.04.001

Yingying Wang , Wenbo Liu , Xiaohan Zhao , Yong Li , Chao Song , Bingjie Huo , Yanru Song , Bibo Tan

As a key protein, Tripartite motif family-like 2 (TRIML2) is crucial to the p53-mediated apoptosis and is correlated with tumorigenesis. Emerging evidence showed that long non-coding RNAs (lncRNAs) play roles in the malignant progression of gastric cancer (GC). However, the function and underlying mechanism of LINC02679 in GC are still unclear. In this study, we detected the differentially expressed lncRNA, LINC02679, which was associated with the progression of GC. Herein, we showed that LINC02679 was overexpressed in GC tissues and correlated with poor prognosis, which aggravated GC proliferation, migration, and invasion. Mechanistically, LINC02679 sponged miR-5004-3p to promote the expression of TRIML2, regulating GC tumorigenesis and progression. Moreover, TRIML2 affected the proliferation, migration, and invasion of GC cells through TGF-β1/Smads signaling pathway. Overall, our findings proved a new mechanism and provided a promising strategy for precise therapy of GC by targeting LINC02679.

Tripartite motif family-like 2 （TRIML2）作为p53介导的细胞凋亡的关键蛋白，与肿瘤发生相关。新出现的证据表明，长链非编码rna （lncRNAs）在胃癌（GC）的恶性进展中发挥作用。然而，LINC02679在GC中的作用和机制尚不清楚。在本研究中，我们检测到了与胃癌进展相关的差异表达lncRNA， LINC02679。本研究发现，LINC02679在胃癌组织中过表达，与预后不良相关，加剧了胃癌的增殖、迁移和侵袭。在机制上，LINC02679海绵miR-5004-3p促进TRIML2的表达，调节GC肿瘤的发生和进展。此外，TRIML2通过TGF-β1/Smads信号通路影响GC细胞的增殖、迁移和侵袭。总之，我们的发现证明了一种新的机制，并为靶向LINC02679精确治疗GC提供了有希望的策略。

引用次数: 0

The mechanism by which MALAT1/CREG1 regulates premature rupture of fetal membrane through autophagy mediated differentiation of amniotic fibroblasts MALAT1/CREG1通过自噬介导的羊膜成纤维细胞分化调控胎膜早破的机制

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-08-01 Epub Date: 2025-04-10 DOI: 10.1016/j.ncrna.2025.04.004

Xiaomei Huang , Ting Huang , Aixing Chen , Yong Shao

Background

Premature rupture of fetal membrane (PROM) is one of the main causes of premature delivery. The amniotic membrane plays a major role in bearing weight, and amniotic fibroblasts play an important role. The purpose of this study was to explore the scientific problems associated with amniotic membrane repair by intervening with fibroblasts to provide evidence for the clinical treatment of PROM.

Methods

This research group conducted experiments on fetal membrane tissue via single-cell sequencing, Sirius staining, fluorescence staining and Raman spectroscopy to explore changes in fetal membrane structure and verified key targets and pathways in clinical tissues and primary fibroblasts through WB, PCR, RNA Pulldown, RIP and molecular docking experiments.

Results

The fetal membrane structure in the PROM group was obviously damaged, and the amniotic fibroblasts were activated and autophagy was activated, and the activated autophagy promoted the activation of fibroblasts. The expression of Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was significantly increased in amniotic fibroblasts. RNA PULL DOWN and molecular docking results suggested that MALAT1 binds to human E1A promoter repressor 1 (CREG1) and promotes autophagy.

Conclusions

By interacting with CREG1, MALAT1 can increase the expression of CREG1, regulate the expression of autophagy-related molecules, mediate the differentiation of amniotic fibroblasts into myofibroblasts, participate in amniotic repair, and promote the repair of PROM fetal membrane tissue.

背景胎膜早破是早产的主要原因之一。羊膜在负重过程中起着重要的作用，而羊膜成纤维细胞也起着重要的作用。本研究旨在探讨成纤维细胞介入羊膜早破修复相关的科学问题，为临床治疗羊膜早破提供依据。方法课课组通过单细胞测序、天狼星染色、荧光染色、拉曼光谱等方法对胎儿膜组织进行实验，探索胎儿膜结构的变化，并通过WB、PCR、RNA Pulldown、RIP、分子对接等实验验证临床组织和原代成纤维细胞中的关键靶点和通路。结果胎膜早破组胎膜结构明显受损，羊膜成纤维细胞被激活，自噬被激活，自噬激活促进成纤维细胞活化。转移相关肺腺癌转录本1 （MALAT1）在羊膜成纤维细胞中的表达显著升高。RNA PULL DOWN和分子对接结果提示MALAT1结合人E1A启动子抑制因子1 （CREG1）并促进自噬。结论MALAT1通过与CREG1相互作用，增加CREG1的表达，调节自噬相关分子的表达，介导羊膜成纤维细胞向肌成纤维细胞分化，参与羊膜修复，促进早膜胎膜组织修复。

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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 : 2025-08-01 Epub 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

CircRNA-based AntimiR therapy: A novel approach to hypertension treatment 基于circrna的抗ir疗法：高血压治疗的新途径

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-08-01 Epub Date: 2025-05-05 DOI: 10.1016/j.ncrna.2025.05.001

Vahideh Tarhriz , Kamran Hosseini , Leila Abkhooie , Eric Lazartigues

The increasing recognition of the types and functions of non-coding RNAs has opened new avenues for their use as novel therapeutic strategies in the treatment of chronic diseases such as hypertension. While most preclinical and clinical studies on hypertension focus on prognosis and treatment, there are still no specific therapeutic approaches for primary and essential hypertension. Modest efficacy and reduced long-term adherence to treatment underscore the need for novel, mechanism-based strategies to address the underlying molecular mechanisms. AntimiRs, as synthetic RNA molecules, and circular RNAs (circRNAs), as naturally occurring RNA species that function as microRNA sponges, could play a crucial role in regulating the renin-angiotensin system (RAS). These non-coding RNAs hold significant potential as innovative approaches for managing primary and essential hypertension. This review aims to provide a comprehensive overview of circRNA-miRNA interactions involved in hypertension regulation via modulation of the RAS, their mechanisms of action, therapeutic advantages, and the major translational challenges, including delivery efficiency, off-target effects, and safety concerns. Optimization of the delivery systems, validating long-term efficacy, and navigating regulatory pathways to bring these promising ncRNA-based therapies closer to preclinical and clinical research of antimiR-based therapies are addressed. Furthermore, this review highlights the potential of these new RNA targets to fill the current therapeutic void and contribute to the advancement of precision medicine in hypertension and related cardiovascular diseases treatment.

对非编码rna类型和功能的日益认识，为其作为治疗高血压等慢性疾病的新治疗策略开辟了新的途径。虽然大多数高血压的临床前和临床研究都集中在预后和治疗上，但对于原发性和原发性高血压仍然没有具体的治疗方法。适度的疗效和较低的长期治疗依从性强调了需要新的、基于机制的策略来解决潜在的分子机制。作为合成RNA分子的anti - irs和作为天然存在的具有微小RNA海绵功能的环状RNA （circRNAs）在调节肾素-血管紧张素系统（RAS）中发挥着至关重要的作用。这些非编码rna作为治疗原发性和原发性高血压的创新方法具有巨大的潜力。本综述旨在全面概述circRNA-miRNA通过RAS调控高血压的相互作用、作用机制、治疗优势以及主要的转化挑战，包括递送效率、脱靶效应和安全性问题。优化递送系统，验证长期疗效，并导航调控途径，使这些有前途的ncrna为基础的治疗更接近临床前和临床研究的抗mir为基础的治疗。此外，本综述强调了这些新的RNA靶点的潜力，以填补目前的治疗空白，并有助于推进精准医学在高血压和相关心血管疾病的治疗。

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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 : 2025-08-01 Epub 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

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 : 2025-08-01 Epub 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

tsRNA, cell death and disease: Connecting the dots tsRNA，细胞死亡和疾病：连接点

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-08-01 Epub Date: 2025-04-29 DOI: 10.1016/j.ncrna.2025.04.006

Xiaoyu Ma, Jiesi Xu, Guoping Li

Cell death is essential for maintaining physiological homeostasis and regulating pathological processes. tRNA-derived small RNAs (tsRNAs), an emerging non-coding small RNA, play key roles in a various form of cell death. The relationship between tsRNAs and diseases has attracted growing attention. However, many challenges remain, particularly in understanding how tsRNAs regulate cell death and their newly discovered roles in these pathways. This paper reviews the generation and classification of tsRNAs and their roles in different diseases through cell death processes, such as ferroptosis, apoptosis, necroptosis, autophagy and pyroptosis. We discuss in detail the dysregulation of tsRNA expression in neurological disorders, metabolic diseases and cancer. We highlight the potential of tsRNAs as biomarkers and therapeutic targets in the context of cell death pathways.

细胞死亡是维持生理稳态和调节病理过程所必需的。trna衍生的小RNA （tsRNAs）是一种新兴的非编码小RNA，在各种形式的细胞死亡中起着关键作用。tsRNAs与疾病的关系越来越受到人们的关注。然而，许多挑战仍然存在，特别是在理解tsRNAs如何调节细胞死亡及其在这些途径中新发现的作用方面。本文综述了tsRNAs的产生、分类及其在不同疾病细胞死亡过程中的作用，如铁坏死、凋亡、坏死、自噬和焦亡。我们详细讨论了tsRNA在神经系统疾病、代谢性疾病和癌症中的表达失调。我们强调tsRNAs在细胞死亡途径背景下作为生物标志物和治疗靶点的潜力。

引用次数: 0

Palmitic acid reduces LDLR-dependent uptake of macrophage-derived extracellular vesicles by hepatoma cells 棕榈酸减少肝癌细胞对巨噬细胞来源的细胞外囊泡的ldlr依赖性摄取

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-08-01 Epub Date: 2025-04-28 DOI: 10.1016/j.ncrna.2025.04.007

Bootsakorn Boonkaew , Nantawat Satthawiwat , Bianca C. Pachane , Lucy M. Brett , Pisit Tangkijvanich , Chaiyaboot Ariyachet

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by a complicated interaction of lipotoxicity and inflammation in the liver, yet the mechanisms linking these phenomena remain incompletely understood. In this study, we investigated the mechanistic uptake of extracellular vesicles (EVs) derived from macrophages into palmitic acid (PA)-induced lipotoxic hepatoma cells. By co-culturing macrophages with lipotoxic Huh7 cells in a transwell system, we demonstrated that PA-treated Huh7 cells exhibited impaired uptake of macrophage-derived EVs. Compared with control Huh7 cells, PA-treated Huh7 cells presented a reduction in the expression of macrophage-derived microRNA-223 (miR-223) after co-culture, accompanied by an increase in the expression of miR-223 target genes. Further analysis revealed that upon PA treatment, the expression of low-density lipoprotein receptor (LDLR) in Huh7 cells and EV uptake activity were simultaneously diminished. Gain- and loss-of-function experiments of LDLR in Huh7 cells revealed a crucial role of LDLR in facilitating EV uptake. Mechanistically, we elucidated that PA induced endoplasmic reticulum stress and subsequently stimulated proprotein convertase subtilisin/kexin type 9 (PCSK9)-mediated LDLR degradation. Administration of a PCSK9 inhibitor rescued LDLR levels and increased EV uptake in PA-treated Huh7 cells from macrophages. Moreover, we found that the uptake of macrophage-derived EVs lacking apolipoprotein E (ApoE) by Huh7 cells was lower than that of control EVs, highlighting the role of ApoE as a facilitator of EV transfer from macrophages into Huh7 cells. Overall, our study highlights the intricate mechanisms underlying EV-mediated communication between macrophages and Huh7 cells during lipotoxicity and provides insight into the development of EV-based therapies for MASLD.

代谢功能障碍相关脂肪变性肝病（MASLD）的特点是肝脏中脂肪毒性和炎症的复杂相互作用，但这些现象之间的联系机制尚不完全清楚。在这项研究中，我们研究了来自巨噬细胞的细胞外囊泡（EVs）进入棕榈酸（PA）诱导的脂毒性肝癌细胞的机制。通过在transwell系统中将巨噬细胞与脂毒性Huh7细胞共培养，我们证明了pa处理的Huh7细胞对巨噬细胞来源的ev的摄取受损。与对照Huh7细胞相比，pa处理的Huh7细胞共培养后巨噬细胞源性microRNA-223 （miR-223）表达降低，miR-223靶基因表达增加。进一步分析发现，PA处理后，Huh7细胞低密度脂蛋白受体（LDLR）的表达和EV摄取活性同时降低。在Huh7细胞中LDLR的功能增益和功能丧失实验揭示了LDLR在促进EV摄取方面的关键作用。在机制上，我们阐明了PA诱导内质网应激并随后刺激枯草素/酶转化蛋白9型（PCSK9）介导的LDLR降解。在pa处理的巨噬细胞Huh7细胞中，给予PCSK9抑制剂可挽救LDLR水平并增加EV摄取。此外，我们发现Huh7细胞对巨噬细胞来源的缺乏载脂蛋白E （ApoE）的EV的摄取低于对照EV，这突出了ApoE作为EV从巨噬细胞转移到Huh7细胞的促进剂的作用。总的来说，我们的研究强调了脂肪毒性过程中巨噬细胞和Huh7细胞之间由ev介导的通讯的复杂机制，并为基于ev的MASLD治疗的发展提供了见解。

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引用次数: 0