Non-coding RNA Research最新文献_第7页

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 : 2025-05-05 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

Alternative transcription increases isoform complexity in Long Non-Coding RNAs and alters their functions in cancer 选择性转录增加了长链非编码rna的异构体复杂性，并改变了它们在癌症中的功能

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-03 DOI: 10.1016/j.ncrna.2025.04.008

Max Bone , Gareth J. Inman

Transcriptional start and end variance, a less-explored aspect of lncRNA biology, is a critical determinant of isoform diversity in human RNA. While alternative splicing (AS) has been extensively studied as a mechanism of isoform generation, differences in transcriptional start and termination site usage—whether from distinct promoters or varying initiation events at the same core promoter—contribute more to isoform diversity than alternative splicing. In the context of long non-coding RNAs (lncRNAs), even subtle alterations to transcriptional start and end sites can induce significant changes in the structural and functional capacities of individual lncRNA isoforms.

This review highlights the underappreciated realm of transcriptional start and end variance in lncRNAs, exploring its pivotal role in shaping the diversity of lncRNA transcripts. In cancer, where lncRNAs are increasingly recognised as key players in tumorigenesis, understanding the ramifications of transcriptional start and end variance is crucial. With single nucleotide alterations capable of influencing the folding energy, shape, stability, and function of a lncRNA molecules, significant changes to transcriptional regulation may lead to aberrant isoforms with implications for cancer initiation, progression, and potentially, its treatment.

As lncRNAs emerge as therapeutic targets, particularly with the advancement of antisense oligonucleotide (ASO) technologies, it becomes crucial to understand the regulatory landscape of transcriptional variation among lncRNA isoforms, to ensure selective targeting of oncogenic transcripts while sparing those with normal physiological functions. By highlighting the significance of transcriptional start and end site variation as major contributors to lncRNA diversity, the potential exploitation for precision therapeutic interventions in the field of non-coding RNA cancer research can be expanded.

转录起始和结束变异是lncRNA生物学中较少探索的一个方面，是人类RNA同工异构体多样性的关键决定因素。虽然选择性剪接（AS）作为异构体产生的一种机制已经被广泛研究，但转录起始位点和终止位点的使用差异——无论是来自不同的启动子还是来自同一核心启动子的不同起始事件——比选择性剪接更能促进异构体多样性。在长链非编码rna （lncRNA）的背景下，即使转录起始位点和结束位点的细微改变也会导致单个lncRNA亚型的结构和功能能力发生重大变化。这篇综述强调了lncRNA转录起始和结束变异的未被充分认识的领域，探讨了其在塑造lncRNA转录物多样性中的关键作用。在癌症中，lncrna越来越被认为是肿瘤发生的关键角色，理解转录起始和结束变异的后果至关重要。由于单核苷酸的改变能够影响lncRNA分子的折叠能量、形状、稳定性和功能，转录调控的重大变化可能导致异常异构体，从而影响癌症的发生、进展，并可能影响其治疗。随着lncRNA成为治疗靶点，特别是随着反义寡核苷酸（ASO）技术的进步，了解lncRNA亚型之间转录变异的调控格局变得至关重要，以确保选择性靶向致癌转录物，同时保留那些具有正常生理功能的转录物。通过强调转录起始位点和结束位点变异作为lncRNA多样性的主要贡献者的重要性，可以扩大对非编码RNA癌症研究领域精确治疗干预的潜在开发。

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引用次数: 0

Uremic toxins levels are associated with miR-223 in chronic kidney disease-associated anemia 慢性肾病相关性贫血患者尿毒症毒素水平与miR-223相关

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-05-02 DOI: 10.1016/j.ncrna.2025.04.009

Emma Brisot , Pierre-Marie Leprêtre , Eya Hamza , Ophélie Fourdinier , Benjamin Brigant , Hakim Ouled-Haddou , Gabriel Choukroun , Ziad A. Massy , Francis Verbeke , Valérie Metzinger-Le Meuth , Griet Glorieux , Laurent Metzinger

Chronic kidney disease (CKD) poses a significant threat, with increased rates of cardiovascular and all-cause mortality. Anemia, common in CKD, is associated with accumulation of uremic toxins in the bloodstream. We previously demonstrated that the uremic toxin indoxyl sulfate (IS) impacts the regulation of erythropoiesis in cellular and preclinical CKD models. Here, the role of non-coding RNAs in this toxic effect was evaluated. The effect of IS on microRNA expression was measured in human erythropoietic cell line UT7/EPO, using nanostring. We found a significant increase of miR-223 in cells treated with IS. This finding was further validated in human primary CD34⁺ cells, a more physiological model for human erythropoiesis. Finally, serum levels of miR-223 correlated with representative uremic toxins, including IS, in patients with various stages of CKD, and also with endothelial dysfunction markers, indicating a link with vascular damage. These correlations varied according to erythropoietin treatment and dialysis. These findings suggest that miR-223 may play a role in the development of anemia in CKD. Further investigation into the involvement of miR-223 in erythropoiesis is needed for a better understanding of the mechanisms underlying anemia in CKD and the potential role of uremic toxins. Ultimately, this may open up new therapeutic possibilities for the management of anemia in CKD.

慢性肾脏疾病（CKD）具有显著的威胁，心血管和全因死亡率增加。慢性肾病中常见的贫血与血液中尿毒症毒素的积累有关。我们之前证明了尿毒症毒素硫酸吲哚酚（IS）在细胞和临床前CKD模型中影响红细胞生成的调节。本研究评估了非编码rna在这种毒性作用中的作用。采用纳米链法检测IS对人红细胞UT7/EPO细胞microRNA表达的影响。我们发现在IS处理的细胞中miR-223显著增加。这一发现在人原代CD34+细胞中得到了进一步验证，这是一种更生理的人红细胞生成模型。最后，在不同阶段CKD患者中，血清miR-223水平与代表性尿毒症毒素（包括IS）相关，也与内皮功能障碍标志物相关，表明与血管损伤有关。这些相关性根据促红细胞生成素治疗和透析而变化。这些发现提示miR-223可能在CKD中贫血的发展中发挥作用。为了更好地了解CKD中贫血的潜在机制和尿毒症毒素的潜在作用，需要进一步研究miR-223在红细胞生成中的作用。最终，这可能为慢性肾病贫血的治疗开辟新的可能性。

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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 : 2025-04-29 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 : 2025-04-28 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

The role of non-coding RNA regulates stem cell programmed death in disease therapy 非编码RNA在疾病治疗中调控干细胞程序性死亡的作用

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-04-23 DOI: 10.1016/j.ncrna.2025.04.005

Ziling Liao , Weidong Liu , Lei Wang , Wen Xie , Chaoyan Yao , Qianping Huang , Xingjun Jiang , Caiping Ren

Programmed cell death (PCD), an essential and inevitable phenomenon, is integral to organismal development. It not only maintains cellular homeostasis but also prevents aberrant cell proliferation, thereby protecting normal growth and development from detrimental factors. And it is governed by a highly complex and sophisticated regulatory network in which non-coding RNAs (ncRNAs) play pivotal roles. ncRNAs refer to RNA molecules that do not encode proteins and encompass various types, including long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). Herein, we investigate the specific signaling mechanisms by which ncRNAs regulate stem cells, elucidating their role in modulating PCD process through interactions with specific molecules. We further summarize the impact of above modulating role on stem cell differentiation, proliferation, cycle regulation and diverse disease development and therapy. Additionally, given the emerging trends in the therapeutic application of ncRNAs and stem cells, we explore the potential of their combined application for disease treatment.

细胞程序性死亡（PCD）是机体发育过程中不可避免的重要现象。它不仅能维持细胞的稳态，还能防止细胞的异常增殖，从而保护正常的生长发育免受有害因素的影响。它是由一个高度复杂和复杂的调控网络控制的，其中非编码rna （ncrna）起着关键作用。ncrna是指不编码蛋白质的RNA分子，包含多种类型，包括长链非编码RNA （lncRNA）、微RNA （miRNA）和环状RNA （circRNA）。在此，我们研究了ncRNAs调节干细胞的特定信号机制，阐明了它们通过与特定分子的相互作用在调节PCD过程中的作用。我们进一步总结了上述调节作用对干细胞分化、增殖、周期调控以及多种疾病发生和治疗的影响。此外，鉴于ncrna和干细胞治疗应用的新趋势，我们探索它们联合应用于疾病治疗的潜力。

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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 : 2025-04-10 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

USF1-activated hsa_circ_0076691 induces oxaliplatin resistance via facilitating FGF9 expression in miR-589-3p-dependent manners usf1激活的hsa_circ_0076691通过促进FGF9以mir -589-3p依赖方式表达诱导奥沙利铂耐药

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-04-08 DOI: 10.1016/j.ncrna.2025.04.003

Lingyu Tang , Xuan Deng , Ming Guan , Liang Zhong

Chemotherapeutic efficacy in colorectal cancer (CRC) is significantly hindered by the development of drug resistance. Emerging evidence indicates that circular RNAs (circRNAs) play pivotal roles in various cancer-related biological processes. Nonetheless, the specific role of circRNAs in oxaliplatin resistance in CRC remains largely unexplored. In this study, hsa_circ_0076691 (circ76691) overexpression was observed in the oxaliplatin-resistant CRC group and could predict poor prognosis. Functional analyses revealed that circ76691 attenuates oxaliplatin-induced apoptosis both in vitro and in vivo, thereby contributing to enhanced oxaliplatin resistance. Mechanistically, circ76691 transcriptionally downregulates miR-589–3p expression and acts as a molecular sponge for miR-589–3p, sequestering it from its downstream targets. Notably, fibroblast growth factor 9 (FGF9), identified as a downstream inhibitory target of miR-589–3p, is subsequently upregulated due to circ76691 activity. Furthermore, circ76691 expression is transcriptionally induced by USF1 through direct binding to its promoter region. Collectively, these findings elucidate the USF1/circ76691/miR-589–3p/FGF9 axis in inhibiting oxaliplatin-induced apoptosis, suggesting circ76691 as a potential therapeutic target to enhance the efficacy of platinum-based therapy.

结直肠癌（CRC）的化疗疗效受到耐药性发展的显著阻碍。新出现的证据表明，环状rna （circRNAs）在各种癌症相关的生物学过程中发挥着关键作用。尽管如此，环状rna在大肠癌患者奥沙利铂耐药中的具体作用在很大程度上仍未被探索。在本研究中，hsa_circ_0076691 （circ76691）在奥沙利铂耐药CRC组中过表达，可预测预后不良。功能分析显示，circ76691在体内和体外均能减弱奥沙利铂诱导的细胞凋亡，从而增强奥沙利铂耐药性。在机制上，circ76691转录下调miR-589-3p的表达，并作为miR-589-3p的分子海绵，将其与下游靶标隔离。值得注意的是，成纤维细胞生长因子9 （FGF9）被认为是miR-589-3p的下游抑制靶点，随后由于circ76691的活性而上调。此外，circ76691的表达是由USF1通过直接结合其启动子区转录诱导的。总之，这些发现阐明了USF1/circ76691/ miR-589-3p /FGF9轴在抑制奥沙利铂诱导的细胞凋亡中的作用，提示circ76691是一个潜在的治疗靶点，可以增强铂基治疗的疗效。

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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 : 2025-04-07 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 : 2025-04-01 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