Non-coding RNA Research最新文献_第8页

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

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

{"title":"HNRNPC stabilizes m6A-modified AC145207.5 to accelerate tumorigenesis in colorectal cancer by impeding the Nrf2/GPX4 axis-mediated ferroptosis","authors":"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","doi":"10.1016/j.ncrna.2025.04.002","DOIUrl":"10.1016/j.ncrna.2025.04.002","url":null,"abstract":"<div><div>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. <em>In vitro</em> experiments including MTS assay, transwell, and colony formation, alongside <em>in vivo</em> 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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 43-56"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

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

{"title":"The emerging role of miRNAs in biological aging and age-related diseases","authors":"Rawad Turko , Amro Hajja , Ahmad M. Magableh , Mohammed H. Omer , Areez Shafqat , Mohammad Imran Khan , Ahmed Yaqinuddin","doi":"10.1016/j.ncrna.2025.05.002","DOIUrl":"10.1016/j.ncrna.2025.05.002","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 131-152"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

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

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

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

{"title":"The mechanism by which MALAT1/CREG1 regulates premature rupture of fetal membrane through autophagy mediated differentiation of amniotic fibroblasts","authors":"Xiaomei Huang , Ting Huang , Aixing Chen , Yong Shao","doi":"10.1016/j.ncrna.2025.04.004","DOIUrl":"10.1016/j.ncrna.2025.04.004","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 29-42"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

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

{"title":"Characterization of small nucleolar RNA retaining transcripts in human normal and cancer cells","authors":"Guglielmo Rambaldelli , Sidra Asghar , Giulia Venturi , Federico Zacchini , Margherita Serra , Catia Giovannini , Laura Gramantieri , Marco Bernini , Alberto Inga , Erik Dassi , Lorenzo Montanaro","doi":"10.1016/j.ncrna.2025.05.004","DOIUrl":"10.1016/j.ncrna.2025.05.004","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 153-161"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

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

{"title":"CircRNA-based AntimiR therapy: A novel approach to hypertension treatment","authors":"Vahideh Tarhriz , Kamran Hosseini , Leila Abkhooie , Eric Lazartigues","doi":"10.1016/j.ncrna.2025.05.001","DOIUrl":"10.1016/j.ncrna.2025.05.001","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 94-108"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

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

{"title":"Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis","authors":"Bruna De Felice , Elisabetta Signoriello , Concetta Montanino , Giuseppe Romano , Deborah Archetto , Elisabetta Maida , Martina Marciano , Simona Bonavita , Giacomo Lus , Federica Farinella , Cinzia Coppola","doi":"10.1016/j.ncrna.2025.05.009","DOIUrl":"10.1016/j.ncrna.2025.05.009","url":null,"abstract":"<div><div>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.</div><div>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.</div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 174-183"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

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

{"title":"Circ_0054633 silencing suppresses hyperglycemia-induced extracellular matrix accumulation in renal mesangial cells by regulating MiR-136-5p/SMAD3 signaling","authors":"Qing Jiang , Hongxin Chen , Ke Wang , Xiaowei Zhu , Jun Yin , Wei Tang","doi":"10.1016/j.ncrna.2025.05.003","DOIUrl":"10.1016/j.ncrna.2025.05.003","url":null,"abstract":"<div><div>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. <em>In</em> <em>vitro</em> experiments, circ_0054633 silencing markedly attenuated hyperglycemia stress-induced cell proliferation and ECM accumulation in human renal mesangial cells). <em>In vivo</em> 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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 84-93"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

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

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

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

{"title":"Palmitic acid reduces LDLR-dependent uptake of macrophage-derived extracellular vesicles by hepatoma cells","authors":"Bootsakorn Boonkaew , Nantawat Satthawiwat , Bianca C. Pachane , Lucy M. Brett , Pisit Tangkijvanich , Chaiyaboot Ariyachet","doi":"10.1016/j.ncrna.2025.04.007","DOIUrl":"10.1016/j.ncrna.2025.04.007","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 71-83"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0