Molecular Therapy. Nucleic Acids最新文献

Retraction Notice to: Long Non-coding RNA Profiling Reveals an Abundant MDNCR that Promotes Differentiation of Myoblasts by Sponging miR-133a. 撤回通知：长非编码RNA分析揭示了丰富的MDNCR通过海绵化miR-133a促进成肌细胞分化。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-09-01 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103079

Hui Li, Jiameng Yang, Rui Jiang, Xuefeng Wei, Chengchuang Song, Yongzhen Huang, Xianyong Lan, Chuzhao Lei, Yun Ma, Linyong Hu, Hong Chen

引用次数: 0

Retraction Notice to: lncRNA TRMP-S directs dual mechanisms to regulate p27-mediated cellular senescence. lncRNA TRMP-S引导双重机制调控p27介导的细胞衰老。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-09-01 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103078

Tian Shuai, Muhammad Riaz Khan, Xu Dong Zhang, Jingmin Li, Rick Francis Thorne, Mian Wu, Fengmin Shao

引用次数: 0

Targeting liver angiotensinogen with siRNA enhances podocyte regeneration through renin lineage cells in experimental kidney disease. 用siRNA靶向肝血管紧张素原促进实验性肾病肾素系细胞足细胞再生。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-08-19 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103065

Loïs A K van der Pluijm, Angela Koudijs, A H Jan Danser, Joris I Rotmans, Roel Bijkerk

{"title":"Targeting liver angiotensinogen with siRNA enhances podocyte regeneration through renin lineage cells in experimental kidney disease.","authors":"Loïs A K van der Pluijm, Angela Koudijs, A H Jan Danser, Joris I Rotmans, Roel Bijkerk","doi":"10.1016/j.omtn.2026.103065","DOIUrl":"10.1016/j.omtn.2026.103065","url":null,"abstract":"Targeting angiotensinogen (AGT) with small interfering RNAs (siRNAs) is a promising strategy to suppress renin-angiotensin system (RAS) activity and to potentially mitigate progression of chronic kidney disease (CKD). Although AGT siRNAs have been shown to exert kidney-protective effects in experimental models of kidney injury, the underlying mechanisms remain unclear. Juxtaglomerular cells of renin lineage (CoRL) have recently been recognized as progenitors capable of replenishing several glomerular cell types during injury. Here, we investigated whether AGT siRNA alters CoRL-driven glomerular cell repopulation in the 5/6 nephrectomy (5/6NX) model using renin lineage-tracing mice treated with either AGT siRNA or luciferase-targeting control. AGT silencing achieved ∼85% reduction in plasma AGT and induced a marked compensatory rise in plasma renin concentration. Despite these systemic effects, AGT knockdown did not alter kidney function, as reflected by unaffected blood urea levels, urinary albumin-to-creatinine ratios, glomerular hypertrophy, or kidney fibrosis. While the number of CoRL-derived mesangial cells remained unchanged, AGT inhibition resulted in a modest but significant increase in CoRL-derived parietal epithelial cells and a pronounced increase in CoRL-derived podocytes. These findings indicate that liver-directed AGT silencing does not confer short-term functional benefit but enhances CoRL-mediated podocyte regeneration, identifying a potential mechanism that may contribute to delayed renal repair.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"37 3","pages":"103065"},"PeriodicalIF":6.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PCBP2 facilitates miR-93-5p-mediated repression of GDF11 in HCC cell lines. PCBP2促进mir -93-5p介导的肝癌细胞系中GDF11的抑制。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-08-19 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103066

Jemin Kim, Soyoung Kim, Minhyuk Yoon, Seung Joon Baek, Chanseok Shin

{"title":"PCBP2 facilitates miR-93-5p-mediated repression of GDF11 in HCC cell lines.","authors":"Jemin Kim, Soyoung Kim, Minhyuk Yoon, Seung Joon Baek, Chanseok Shin","doi":"10.1016/j.omtn.2026.103066","DOIUrl":"10.1016/j.omtn.2026.103066","url":null,"abstract":"Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β superfamily, functions in skeletal muscle and neuronal regeneration and has been implicated in tumor suppression. In hepatocellular carcinoma (HCC), GDF11 expression is markedly downregulated, but the mechanisms responsible for this repression remain unclear. In this study, we examined whether the oncogenic miR-106b-25 cluster contributes to GDF11 suppression in HCC. We found that this cluster decreases GDF11 expression at both the mRNA and protein levels, with miR-93-5p acting as the dominant regulator. Inhibition of miR-93-5p with antisense oligonucleotides restored GDF11 expression and reduced HCC cell proliferation, migration, and invasion. Mechanistically, we identified the RNA-binding protein (RBP) PCBP2 as a key facilitator of miR-93-5p targeting of GDF11. PCBP2 binds a C-rich element adjacent to the miR-93-5p target site in the GDF11 3' UTR, thereby enhancing miR-93-5p-mediated repression. PCBP2 knockout attenuated miR-93-5p-mediated repression, whereas re-expression of PCBP2 restored it, supporting its modulatory role. Collectively, these findings identify PCBP2 as a modulator of miR-93-5p-mediated GDF11 repression and suggest that this regulatory interaction contributes to HCC cell proliferation, migration, and invasion. This work provides insights into the post-transcriptional control of the tumor suppressor and highlights the therapeutic potential of targeting miRNA-RBP interactions.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"37 3","pages":"103066"},"PeriodicalIF":6.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miRNA-34a-5p is a novel biomarker and modulator of the radioresponse in esophageal adenocarcinoma. miRNA-34a-5p是食管癌放射反应的新型生物标志物和调节剂。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-08-18 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103064

Christina Cahill, David Hackett, Laura E Kane, James J Phelan, Jason McGrath, Maitiú Ó Murchú, Aoife Cannon, Aisling B Heeran, Aoife Kilgallon, Rebecca Lyons, Rebecca M O'Brien, Wei-Lin Winnie Wang, Meghana S Menon, Oana M Deac, Antonia Tierney, Narayanasamy Ravi, Claire Donohoe, Dermot O'Toole, Cian Muldoon, Aoife Maguire, Joanne Lysaght, Maeve A Lowery, John V Reynolds, Stephen G Maher, Jacintha O'Sullivan, Niamh Lynam-Lennon

{"title":"miRNA-34a-5p is a novel biomarker and modulator of the radioresponse in esophageal adenocarcinoma.","authors":"Christina Cahill, David Hackett, Laura E Kane, James J Phelan, Jason McGrath, Maitiú Ó Murchú, Aoife Cannon, Aisling B Heeran, Aoife Kilgallon, Rebecca Lyons, Rebecca M O'Brien, Wei-Lin Winnie Wang, Meghana S Menon, Oana M Deac, Antonia Tierney, Narayanasamy Ravi, Claire Donohoe, Dermot O'Toole, Cian Muldoon, Aoife Maguire, Joanne Lysaght, Maeve A Lowery, John V Reynolds, Stephen G Maher, Jacintha O'Sullivan, Niamh Lynam-Lennon","doi":"10.1016/j.omtn.2026.103064","DOIUrl":"10.1016/j.omtn.2026.103064","url":null,"abstract":"Poor pathological response to neoadjuvant chemoradiotherapy (neo-CRT) remains a major clinical challenge in esophageal adenocarcinoma (EAC), contributing to treatment resistance and poor patient outcomes. Identification of novel predictive biomarkers of treatment resistance and therapeutic targets to enhance treatment response are crucial to improving patient outcomes. In this study, we investigated the role of miR-34a-5p in EAC treatment response using both cell line models and clinical tumor samples. We observed reduced miR-34a-5p expression across multiple cell line models of radioresistant EAC. Overexpression of miR-34a-5p enhanced radiosensitivity, impaired DNA damage repair, and altered cell cycle following irradiation, accompanied by changes in the expression of DNA damage response and cell cycle-related genes. Consistent with these findings, analysis of pre-treatment tumor biopsies from EAC patients demonstrated that reduced miR-34a-5p expression was associated with poor response to neo-CRT, advanced pathological T stage, and worse clinical outcomes. This study demonstrates for the first time, a role for miR-34a-5p as a potential biomarker of treatment response and an independent predictor of survival outcomes in EAC patients. Furthermore, we identify miR-34a-5p as a radiosensitizer in EAC, highlighting a novel therapeutic approach to enhance the efficacy of radiation therapy in EAC.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"37 3","pages":"103064"},"PeriodicalIF":6.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages. 新一代巨噬细胞工程在癌症治疗中的应用：从TAM重编程到car巨噬细胞。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-08-14 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103060

Olga Nilova, Anna Zajakina

{"title":"Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.","authors":"Olga Nilova, Anna Zajakina","doi":"10.1016/j.omtn.2026.103060","DOIUrl":"10.1016/j.omtn.2026.103060","url":null,"abstract":"Macrophages are central regulators of the tumor microenvironment (TME), shaping immune suppression, angiogenesis, metabolism, and therapeutic resistance in solid cancers. While early strategies sought to deplete tumor-associated macrophages (TAMs) or block monocyte recruitment, limited efficacy and compensatory mechanisms revealed the need for functional reprogramming rather than elimination. Recent advances in viral vectors, CRISPR-Cas genome editing, and RNA-based delivery platforms have enabled precise genetic modification of macrophages, giving rise to chimeric antigen receptor macrophages (CAR-Ms) and related engineered products. Beyond antigen targeting, effective macrophage engineering requires stabilization of pro-inflammatory identity, resistance to tumor-induced repolarization, metabolic reinforcement, and integration of checkpoint modulation pathways. This review synthesizes current strategies across DNA, mRNA, and siRNA-based platforms, highlighting convergent design principles that connect TAM reprogramming with CAR-M development. We discuss reshaping phagocytosis checkpoints, metabolic and transcriptional stabilization, cytokine augmentation, and synthetic receptor architecture, emphasizing combinatorial and context-aware engineering, while proposing new candidate gene targets. Engineered macrophages are thus evolving from simple effector cells into programmable immune coordinators capable of converting immunologically \"cold\" tumors into inflamed, therapy-responsive niches.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"37 3","pages":"103060"},"PeriodicalIF":6.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual recognition drives site-directed G-quadruplex stabilization: Oligonucleotide design in G4 ligand-oligonucleotide conjugates. 双重识别驱动定点g -四联体稳定：G4配体-寡核苷酸偶联物的寡核苷酸设计。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-08-14 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103061

Alva Abrahamsson, Sakina Khwaja, Namrata Chaudhari, Steven Vertueux, Andreas Berner, Koit Aasumets, Chandan Kumar, Lotte Stietz, Tom Baladi, Anders Dahlén, Sjoerd Wanrooij, Erik Chorell

{"title":"Dual recognition drives site-directed G-quadruplex stabilization: Oligonucleotide design in G4 ligand-oligonucleotide conjugates.","authors":"Alva Abrahamsson, Sakina Khwaja, Namrata Chaudhari, Steven Vertueux, Andreas Berner, Koit Aasumets, Chandan Kumar, Lotte Stietz, Tom Baladi, Anders Dahlén, Sjoerd Wanrooij, Erik Chorell","doi":"10.1016/j.omtn.2026.103061","DOIUrl":"10.1016/j.omtn.2026.103061","url":null,"abstract":"G-quadruplex (G4) DNA structures are increasingly recognized for their roles in transcriptional regulation and genome stability, making them attractive therapeutic targets. Selective recognition of individual G4s remains challenging due to the high structural similarity among G4 motifs. G4 Ligand-Oligonucleotides conjugates (GL-Os) address this challenge by combining small-molecule G4 ligands with the sequence specificity of oligonucleotides, targeting sequences flanking the intended G4 target. Here, we systematically investigate how oligonucleotide length, backbone composition, and sequence complementarity govern GL-O binding, selectivity, and G4 stabilization. We show that effective G4 recognition depends on the interdependence between oligonucleotide hybridization and G4 ligand binding, such that both elements cooperatively reinforce complex stability and site specificity. Longer oligonucleotides promote more stable complexes and stronger G4 stabilization, whereas central mismatches disrupt this dual-recognition mechanism. Replacement of DNA with peptide nucleic acids (PNAs) enhances binding strength, thermal stability, and metabolic stability. Importantly, ligand conjugation redirects PNA oligonucleotides from nonspecific polymerase stalling toward selective G4 stabilization. Finally, we demonstrate receptor-mediated cellular uptake of modified GL-Os, supporting the feasibility of cellular delivery while highlighting remaining delivery barriers. Together, these findings show the molecular design principles governing GL-O behavior and provide a foundation for the future development and evaluation of selective G4-targeting therapeutics.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"37 3","pages":"103061"},"PeriodicalIF":6.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vivo genome editing of central nervous system SIV reservoirs in ART-suppressed rhesus macaques. art抑制恒河猴中枢神经系统SIV库的体内基因组编辑。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-08-14 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103063

Hong Liu, Shuren Liao, Chen Chen, Wenwen Huo, Zahra Safaei, Angela Rocchi, Yuru Huang, Ilker K Sariyer, Mackenzie E Collins, Jill M Lawrence, Will Dampier, Michael R Nonnemacher, Brian Wigdahl, Tricia H Burdo, Jennifer Gordon, Mark Lewis, Cheri A Lee, Kamel Khalili

{"title":"In vivo genome editing of central nervous system SIV reservoirs in ART-suppressed rhesus macaques.","authors":"Hong Liu, Shuren Liao, Chen Chen, Wenwen Huo, Zahra Safaei, Angela Rocchi, Yuru Huang, Ilker K Sariyer, Mackenzie E Collins, Jill M Lawrence, Will Dampier, Michael R Nonnemacher, Brian Wigdahl, Tricia H Burdo, Jennifer Gordon, Mark Lewis, Cheri A Lee, Kamel Khalili","doi":"10.1016/j.omtn.2026.103063","DOIUrl":"10.1016/j.omtn.2026.103063","url":null,"abstract":"Latent human immunodeficiency virus type 1 (HIV-1) reservoirs in the central nervous system (CNS) may sustain viral persistence and neuroinflammation contributing to HIV-associated neurocognitive disorders (HAND) despite suppressive ART. AAV9-delivered CRISPR has successfully edited SIV proviral DNA in peripheral tissues with acceptable safety profiles, but the extent of in vivo genome editing in the brain remains unclear. Using SIV-infected rhesus macaques, we mapped intact proviral DNA across CNS regions and tested systemic AAV9-CRISPR-Cas9 targeting conserved sites within Ψ packaging signal and Gag region. Ten adult rhesus macaques were infected with genetically barcoded SIVmac239, suppressed with ART, then randomized to receive intravenous AAV9-SaCas9 with dual gRNAs (Ψ + Gag) or a Cas9-only control. At necropsy after viral rebound, SIV genomes were detected in multiple brain regions as well as lymphoid tissues, confirming the CNS as a persistent reservoir during ART. Barcode analysis revealed region-specific patterns consistent with compartmentalized CNS persistence. In CRISPR-treated animals, proviral editing was measurable across anatomically distinct CNS sites. These findings demonstrate that intact and potentially replication-competent virus persists in the primate brain under ART and that systemic AAV9-CRISPR can reach and edit proviral DNA in this sanctuary, supporting genome editing as a strategy toward durable remission of CNS reservoirs.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"37 3","pages":"103063"},"PeriodicalIF":6.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety and toxicity assessment of antisense oligonucleotides in brain-relevant human cellular models. 反义寡核苷酸在脑相关人细胞模型中的安全性和毒性评价。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-08-13 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103062

Laura Colar Zanjko, Raúl Andrés-Santamaria, Andrea Balogh, Willeke M C van Roon-Mom, András Dinnyés

{"title":"Safety and toxicity assessment of antisense oligonucleotides in brain-relevant human cellular models.","authors":"Laura Colar Zanjko, Raúl Andrés-Santamaria, Andrea Balogh, Willeke M C van Roon-Mom, András Dinnyés","doi":"10.1016/j.omtn.2026.103062","DOIUrl":"10.1016/j.omtn.2026.103062","url":null,"abstract":"Antisense oligonucleotides (ASOs) have become an established therapeutic modality for central nervous system (CNS) disorders, enabling selective modulation of gene expression through splice-switching or steric-hindrance mechanisms. Backbone and sugar chemistry modifications improved nuclease resistance, tissue retention, and pharmacodynamic durability, facilitating clinical translation of intrathecally delivered ASOs. This review summarizes current in vitro approaches for assessing safety and toxicity of CNS-targeted ASOs, alongside the evolving regulatory landscape shaping their preclinical evaluation. Human-relevant platforms-induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, and brain organoids-enable evaluation of target engagement, cytotoxicity, and immune activation in disease-relevant genetic backgrounds, though each carries distinct trade-offs in throughput, maturity, and translational fidelity. Delivery strategies and cytotoxicity assays, including calcium imaging, lactate dehydrogenase release, metabolic activity measurements, apoptosis markers, and transcriptomic and proteomic profiling, allow detection of sequence- and chemistry-dependent liabilities, including off-target and neuroexcitability effects. Emerging evidence demonstrates sequence and chemical modifications predicting acute neurotoxicity, highlighting the value of systematic in vitro screening. As personalized \"n-of-1\" ASO therapies expand, robust and standardized in vitro safety profiling becomes increasingly critical. Comprehensive evaluation in relevant CNS models will be essential to minimize risk and improve translational predictability for developing safe and effective ASO treatments for neurological diseases.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"37 3","pages":"103062"},"PeriodicalIF":6.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low circulating miR-5193 promotes PD-L1-mediated immune evasion and relates to immune checkpoint inhibitor response in esophageal cancer. 低循环miR-5193促进pd - l1介导的免疫逃避，并与食管癌免疫检查点抑制剂反应有关。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2026-08-12 eCollection Date: 2026-09-08 DOI: 10.1016/j.omtn.2026.103059

Ryo Ishida, Shuhei Komatsu, Hajime Kamiya, Takuma Ohashi, Taisuke Imamura, Jun Kiuchi, Keiji Nishibeppu, Yusuke Takashima, Hiroshi Arakawa, Masateru Yamauchi, Satoshi Hamada, Hiroyuki Kanazawa, Hiroki Shimizu, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Hitoshi Fujiwara, Tomoko Iehara, Hitoshi Tsuda, Atsushi Shiozaki

{"title":"Low circulating miR-5193 promotes PD-L1-mediated immune evasion and relates to immune checkpoint inhibitor response in esophageal cancer.","authors":"Ryo Ishida, Shuhei Komatsu, Hajime Kamiya, Takuma Ohashi, Taisuke Imamura, Jun Kiuchi, Keiji Nishibeppu, Yusuke Takashima, Hiroshi Arakawa, Masateru Yamauchi, Satoshi Hamada, Hiroyuki Kanazawa, Hiroki Shimizu, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Hitoshi Fujiwara, Tomoko Iehara, Hitoshi Tsuda, Atsushi Shiozaki","doi":"10.1016/j.omtn.2026.103059","DOIUrl":"10.1016/j.omtn.2026.103059","url":null,"abstract":"Low levels of circulating tumor-suppressor microRNAs are associated with cancer progression and poor prognosis. However, their role in immune evasion and response to immune checkpoint inhibitors (ICIs) remains unclear. We aimed to identify a PD-L1-targeting tumor-suppressor microRNA downregulated in esophageal squamous cell carcinoma (ESCC). Four tumor-suppressor microRNAs (miR-5193, miR-3117-3p, miR-802, and miR-651-3p) predicted to target programmed cell death ligand 1 (PD-L1) were selected. Plasma levels of miR-5193 were significantly lower in ESCC patients than in healthy volunteers. In 122 consecutive ESCC patients, low plasma miR-5193 was associated with advanced tumor depth and pathological stage and was an independent prognostic factor. In ESCC cells, miR-5193 suppressed PD-L1 expression. In a co-culture model of tumor cells and T cells, miR-5193 overexpression enhanced T cell antitumor activity by suppressing PD-L1. Among 56 ESCC patients treated with or without ICIs for recurrence, miR-5193 levels showed a trend toward an inverse association with PD-L1 tumor proportion score. In the low miR-5193 group, disease control rate was higher and ICI-treated patients showed a trend toward longer progression-free survival. Low levels of miR-5193 contribute to ESCC progression and poor outcomes and may serve as a biomarker reflecting tumor immune status and ICI-related outcomes.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"37 3","pages":"103059"},"PeriodicalIF":6.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0