Non-Coding RNA最新文献

{"title":"Circular RNAs in Neurons: From Transport to Function.","authors":"Nicolò Salvi, Mariangela Morlando","doi":"10.3390/ncrna12040027","DOIUrl":"10.3390/ncrna12040027","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) have recently emerged as a class of abundant and remarkably stable non-coding RNAs preferentially enriched in the nervous system. In neurons, the fine-tuned spatial regulation of gene expression is critical for proper synaptic function; accordingly, several studies have demonstrated that circRNAs exhibit highly compartmentalized localization, specifically within dendrites, axons, and synapses. These spatial localization properties imply the presence of active transport mechanisms, which control the intracellular trafficking of circRNAs. This review highlights the current understanding of circRNA transport in neurons, focusing on the molecular machinery driving synaptic enrichment. We explore the potential role of ribonucleoprotein-based transport as a primary mechanism driving circRNA localization and examine how such spatial distribution influences synaptic plasticity and post-transcriptional gene regulation. Finally, we discuss the clinical implications of these processes, exploring the link between dysregulated RNA transport and the development of neuronal abnormalities.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Bioengineered PD-L1 siRNA for Immunotherapy Against Non-Small Cell Lung Cancer Cells.","authors":"Neelu Batra, Mei-Juan Tu, Su Guan, Jonathan W Riess, Ai-Ming Yu","doi":"10.3390/ncrna12040026","DOIUrl":"10.3390/ncrna12040026","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Recent advances in immunotherapy have revolutionized cancer treatment, as exemplified by multiple monoclonal antibodies against programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1). Nevertheless, immunotherapeutic antibodies exhibit certain limitations, which drives the development of alternative approaches, such as small interfering RNA (siRNA)-based therapeutics. The aim of this study was to design and produce new biological PD-L1 siRNA (BioRNA/PD-L1-siRNA) molecules and further define their immunotherapeutic efficacy against non-small cell lung cancer (NSCLC) in vitro. <b>Methods</b>: A novel RNA molecular bioengineering platform was employed to produce new BioRNA/PD-L1-siRNA agents. The functions of BioRNA/PD-L1-siRNAs were determined by quantitative PCR, Western blot, immunofluorescence confocal imaging, flow cytometry, and PD-1/PD-L1 blockade assays in human NSCLC cells, alone and co-cultured with human peripheral blood mononuclear cells (PBMCs). <b>Results</b>: After heterologous overexpression and purification of five BioRNA molecules, one siRNA named BioRNA/PD-L1-siRNA-1 was identified as the most effective to selectively suppress human PD-L1 mRNA and protein levels in H460 and H1975 cells. Disruption of PD-1/PD-L1 interactions by BioRNA/PD-L1-siRNA-1 was further demonstrated via a PD-1/PD-L1 blockade bioassay. In addition, the immunomodulatory effectiveness of BioRNA/PD-L1-siRNA-1 was established in co-culture models, as indicated by the induction of T-cell and natural killer cell populations and an increase in specific cytokines and cytotoxic granules, and subsequent enhancement of apoptosis and greater inhibition of NSCLC cell viability. <b>Conclusions</b>: Overall, these findings demonstrate the potential of bioengineered PD-L1 siRNA entities for NSCLC immunotherapy.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MeCP2 Dosage Control in Rett Syndrome: Non-Coding RNA-Based and Epigenetic Strategies for Safer Gene Therapy.","authors":"Ilyas M Kabdesh, Albert A Rizvanov, Yana O Mukhamedshina","doi":"10.3390/ncrna12040025","DOIUrl":"10.3390/ncrna12040025","url":null,"abstract":"<p><p>Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that is caused in most cases by pathogenic variants in <i>MECP2</i>, the gene encoding methyl-CpG-binding protein 2 (MeCP2). Despite substantial progress in the development of gene therapy, restoring <i>MECP2</i> expression remains challenging because MeCP2 is highly dosage-sensitive. Both deficiency and excessive expression of this protein are associated with severe neurological abnormalities. This makes simple viral vector-mediated replacement of <i>MECP2</i> potentially unsafe and underscores the need for multilayered systems that control transgene expression. This review discusses current and emerging strategies for regulating MeCP2 expression in RTT, with an emphasis on non-coding RNA-based and epigenetic mechanisms. Particular attention is given to the limitations of conventional AAV-mediated gene therapy, the use of cell-specific and endogenous promoters, miRNA-regulated elements, autoregulatory systems, and post-transcriptional control of <i>MECP2</i> expression. Strategies for reactivating the inactive X chromosome are also discussed, including XIST-dependent regulation and epigenome editing. In addition, the review considers CRISPR-mediated regulation, selective epigenetic activation, and combined therapeutic platforms that integrate viral delivery, RNA-dependent post-transcriptional control, and endogenous gene regulation. Overall, clinically applicable gene therapy for RTT will likely need to move beyond simple <i>MECP2</i> replacement and instead rely on precise cell- and dose-dependent regulation of its expression. Non-coding RNA and epigenetic mechanisms represent important layers of such control and may contribute to the development of safer gene therapy strategies for RTT.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Transcriptomic, In Silico, and In Vitro Characterization of lncRNA ENST00000615487.1 Reveals Epithelial-Specific Expression, Differential Subcellular Distribution Between Normal and Colorectal Cancer Cells, and Potential Regulatory Functions.","authors":"Nataša Đokić, Anastasija Bubanja, Jelena Karanović, Jovana Despotović","doi":"10.3390/ncrna12040024","DOIUrl":"10.3390/ncrna12040024","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Long non-coding RNAs (lncRNAs) are important regulators of tumor biology through their interactions with DNA, proteins, and non-coding RNAs. Although ENST00000615487.1 (also known as CTD-2396E7.11/AC010503.4) has been associated with multiple malignancies, its biological role in colorectal cancer (CRC) remains poorly characterized. This study aimed to investigate the expression pattern, cellular and subcellular localization, and potential functional role of ENST00000615487.1 in CRC using integrated in vitro and in silico approaches. <b>Methods</b>: Molecular characteristics of the transcript were obtained with the CPC2 and RNA Analyzer 3 tools. Differential expression of ENST00000615487.1 across 10 tumor types was analyzed using the UCSC Xena Browser. Transcript expression was experimentally evaluated in normal, tumor, and fibroblastic colon cell lines by PCR, while subcellular localization was assessed through the lncATLAS, lncLocator, and iLoc-LncRNA tools, and experimentally confirmed by qRT-PCR. Single-cell RNA sequencing data from the GSE161277 dataset were analyzed to determine cell type-specific expression patterns. Potential interactions with DNA, miRNAs, and proteins were investigated using Fasim-LongTarget, miRDB, and AnnoLnc2, followed by functional enrichment analyses using STRING and Enrichr. <b>Results</b>: ENST00000615487.1 was identified as a structurally stable non-coding transcript with a highly organized secondary structure. Differential expression analysis demonstrated significant downregulation in CRC compared with that in normal colon tissue. Single-cell transcriptomic analysis revealed predominantly epithelial-specific expression. In silico and experimental analyses demonstrated predominant nuclear localization in normal colon cells, whereas cytoplasmic enrichment was observed in CRC cells. Functional analyses identified potential interactions with <i>HIP1R</i>, <i>RPH3AL</i>, specific miRNAs, and proteins involved in transcriptional regulation and RNA processing pathways, as well as functional connections with proteins involved in vesicular transport. <b>Conclusions</b>: ENST00000615487.1 is a structurally stable lncRNA exhibiting context-dependent expression and localization patterns in CRC, suggesting a potential shift from nuclear transcriptional regulation toward cytoplasmic post-transcriptional functions during colorectal carcinogenesis.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The <i>Non-Coding RNA</i> Journal Club: Highlights on Recent Papers-15.","authors":"Francisco J Enguita, Suresh K Alahari, Luca Agnelli, Raphaël Zemmour, Florent Hubé, Patrick K T Shiu, Sophia M Zhang, Mohammadjavad Mohammadi, Shuxing Zhang, Sreyasree Dhar, Simon J Conn, Agnieszka Bronisz, Jakub Godlewski, Abhishek Kaushik, Alexander Serganov, Barbara Pardini, André P Gerber, Mark W Feinberg, Eleonora Leucci, Phoebe Philpott, Andrea Caporali, Toshiaki Takahashi, Ajay Goel, Ling Yang","doi":"10.3390/ncrna12040023","DOIUrl":"10.3390/ncrna12040023","url":null,"abstract":"<p><p>We are delighted to share with you our fifteenth Journal Club and highlight some of the most interesting papers published recently [...].</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Mathematical Approach on the Limits of ceRNA Hypothesis Through an Ordinary Differential Equations (ODE) Model of mRNA-microRNA Interactions.","authors":"Paul Flondor, Mircea Olteanu, Radu Stefan, Corina Elena Minciuna, Catalin Vasilescu","doi":"10.3390/ncrna12040022","DOIUrl":"10.3390/ncrna12040022","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to target messenger RNAs (mRNAs) and suppressing their expression. Competing endogenous RNAs (ceRNAs), including mRNAs and circular RNAs (circRNAs), modulate miRNA availability through competitive binding, forming regulatory networks that fine-tune gene expression. CircRNAs can act as miRNA sponges, reducing miRNA-mediated repression of other targets, a mechanism implicated in various pathophysiological processes, including oncogenesis.</p><p><strong>Methods: </strong>We propose a mathematical model describing the dynamics of miRNA-mRNA-protein interactions, extending existing frameworks for miRNA-mRNA regulation. A qualitative analysis of the associated nonlinear differential equations system is performed.</p><p><strong>Results: </strong>We prove the boundedness of all positive solutions, establish the existence of a unique positive attracting equilibrium, and provide a mathematical perspective on the crosstalk mechanism in protein production.</p><p><strong>Conclusions: </strong>The effectiveness of ceRNA interactions depends on the relative abundance of miRNAs and their targets. This highlights the ongoing debate regarding the biological impact of low-abundance RNA transcripts on miRNA-mediated regulation.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P22 Small Noncoding RNAs Are Actively Secreted in <i>Salmonella</i> Outer Membrane Vesicles During Bacteriophage Infection.","authors":"Sayema Naaz, Haley A Kominek, Lydia A Hayes-Guastella, Autumn M McDaniel, Enas S Alsatari, Adeyeye I Haastrup, Olivia G Clark, Devin M Katerski, Francois O Prinsloo, Olivia R Roberts, Meredith A Shaddix, Bridgette N Sullivan, Isabella M Swan, Emily M Hartsell, Jeffrey D DeMeis, Suhas S Patil, Richard H Pham, Makala R Cox, Glen M Borchert","doi":"10.3390/ncrna12040021","DOIUrl":"10.3390/ncrna12040021","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Outer membrane vesicles (OMVs) are membrane-encapsulated spherical structures ~120 nm in diameter derived from Gram-negative bacterial cell envelopes. OMVs are primarily generated by outer membrane blebbing but contain proteins, DNA, and RNAs at concentrations distinct from that of the intracellular complement. OMVs have been associated with a number of different cellular functions including intercellular communication and resistance to phage. <b>Methods</b>: As bacterial small RNAs (sRNAs) also participate in bacteriophage defense and are specifically delivered to and enriched in OMVs, we recently elected to examine the effects of P22 infection on Salmonella cytosolic and OMV sRNA abundance by employing RNA sequencing. <b>Results</b>: We find that P22 infection triggers a global reduction in sRNAs (with Salmonella sRNA expression levels averaging only 15.6% those observed in noninfected cells) coupled with a reciprocal 72.7% global increase in Salmonella tRNA expression levels. Additionally, of note, while OMV small noncoding RNA (sncRNA) abundance is normally ~1/10 that found in the cytosol, we find that P22 infection triggers active OMV encapsulation and secretion of: (1) a subset of sRNAs, (2) all Salmonella tRNAs including one highly complementary to the P22 genome, and, much to our surprise, (3) ten distinct sRNAs expressed from P22. <b>Conclusions</b>: In summary, the work presented here identifies several Salmonella sncRNA cytosolic and/or OMV abundances significantly altered during P22 infection, and to our knowledge, this constitutes the first reported characterization of bacteriophage-encoded sRNAs being actively secreted within host OMVs.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Optimized RT-qPCR Protocol for Comprehensive Analysis of microRNAs and mRNAs in <i>Mus musculus</i> Brain Tissues.","authors":"Maria V Lukashevich, Margarita M Rudenok, Suzanna A Partevian, Maria I Shadrina, Petr A Slominsky, Anelya Kh Alieva","doi":"10.3390/ncrna12030020","DOIUrl":"10.3390/ncrna12030020","url":null,"abstract":"<p><p><b>Background/Objectives:</b> MicroRNAs are key post-transcriptional regulators involved in various diseases. Despite its status as the gold standard, real-time RT-PCR faces challenges arising from high sequence homology among closely related microRNAs and the substantial biomaterial required to enrich small RNA fractions. This study aimed to develop an optimized protocol for simultaneous analysis of microRNA and mRNA expression from a single total RNA sample using mouse (<i>Mus musculus</i>) brain tissue, avoiding dependence on pre-designed commercial assay panels. <b>Methods:</b> We optimized a real-time RT-PCR workflow enabling simultaneous analysis of mature microRNAs and mRNAs from a single total RNA sample. Modifications include a redesigned universal reverse primer, LNA-modified TaqMan probes, and omission of the 65 °C denaturation step during reverse transcription. The method was validated for five microRNAs in mouse brain tissue. <b>Results:</b> The assay showed high specificity, discriminating closely related <i>miR-125a-5p</i> and <i>miR-125b-5p</i> with a ΔCt difference of 6.7 ± 1.2 cycles. Co-analysis with Oligo(dT)₁₈ and Random hexamer primers did not interfere with microRNA detection. <b>Conclusions:</b> The developed approach enables reliable detection of closely related microRNAs and parallel analysis of different RNA types, which is particularly important for studying regulatory networks when working with limited amounts of biomaterial. This protocol provides a complementary, accessible option for targeted studies in resource-limited settings or for non-cataloged miRNA targets.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13304521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Long Non-Coding RNAs <i>H19</i> rs3741219, <i>MEG3</i> rs7158663, <i>POLR2E</i> rs3787016, and <i>ANRIL</i> rs10757274 with Breast Cancer Susceptibility and Clinicopathological Characteristics in a Mexican Population.","authors":"Mónica Alejandra Rosales-Reynoso, Anilú Margarita Saucedo-Sariñana, Clara Ibet Juárez-Vázquez, César de Jesús Tovar-Jácome, Rubria Alicia González-Sánchez, Karen Guadalupe Mestas-Villagran, Gustavo Andrés Torres-Sánchez, José Elías García-Ortíz, Efraín Salas-González, Martha Patricia Gallegos-Arreola","doi":"10.3390/ncrna12030019","DOIUrl":"10.3390/ncrna12030019","url":null,"abstract":"<p><p>Recent evidence has highlighted the crucial role of non-coding genetic elements in regulating gene expression and has been linked to a broad range of biological functions. Notably, dysregulation of long non-coding RNAs has been strongly associated with tumorigenesis and cancer progression. <b>Background/Objectives</b>: This study aimed to investigate the potential association between the <i>H19</i> rs3741219 T>C, <i>MEG3</i> rs7158663 G>A, <i>POLR2E</i> rs3787016 T>C, and <i>ANRIL</i> rs10757274 A>G variants and Breast Cancer (BC) susceptibility, as well as their relationship with clinicopathological characteristics in Mexican patients. <b>Methods</b>: DNA was obtained from peripheral blood samples of 505 women (254 patients and 251 control females). Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methodology. Associations were calculated using odds ratios (ORs), with <i>p</i>-values adjusted by the Bonferroni test (<i>p</i> < 0.012). In silico analyses were conducted to predict the functional impact of the variants associated. <b>Results</b>: Patients carrying the C/C genotypes in <i>H19</i> rs3741219 and <i>POLR2E</i> rs3787016 variants showed increased susceptibility to developing BC and with clinical and pathological characteristics (age at diagnosis, TNM stage, histologic type and molecular subtype) (<i>p</i> < 0.001). <b>Conclusions</b>: The results suggest that <i>H19</i> rs3741219 and <i>POLR2E</i> rs3787016 variants significantly influence BC risk.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive lincRNA Transcriptome in Acute Myeloid Leukemia: Integrating Known and Newly Identified lincRNAs Across Pediatric and Adult Cohorts.","authors":"Saioa Arza-Apalategi, Daan Gilissen, Anne C van der Grinten, Seline N van den Oever, Erik B van den Akker, Marieke Griffioen, Joop H Jansen, Joost H A Martens, Anna E Marneth, Bert A van der Reijden","doi":"10.3390/ncrna12030018","DOIUrl":"10.3390/ncrna12030018","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Acute myeloid leukemia (AML) comprises genetic subclasses with distinct gene expression profiles. While AML gene expression studies have mainly focused on protein-coding genes, our understanding of expression patterns of long intergenic noncoding RNAs (lincRNAs) remains incomplete. This is due to limited sample sizes, as well as incomplete annotation of lncRNAs with context-dependent expression. <b>Methods</b>: To address this gap, we developed the bioinformatic pipeline LIRA (long intergenic noncoding RNA annotator) to identify novel lincRNAs using stringent criteria, including spliced and intergenic transcripts, and algorithms to exclude coding potential. <b>Results</b>: By applying LIRA to RNA-sequencing data from 878 pediatric and adult AML cases and 20 healthy controls, we identified 1560 novel lincRNAs, expanding the GENCODE v38 lincRNA catalog by 27%. Integration of in-house-generated CAGE- and ChIP-sequencing data from KMT2A::MLLT3 samples revealed that 80% of the novel lincRNAs are 5' capped, and at least 67% harbor activating epigenetic marks at their transcription start sites. Unsupervised analysis of the 1000 most variable known and newly identified lincRNAs uncovered subclass-specific expression patterns, mirroring those observed for protein-coding genes. Weighted Gene Co-expression Network Analysis identified 17 lincRNA expression modules associated with AML subclasses. Notably, expression of these modules decreased upon degradation of the leukemogenic onco-fusion proteins KMT2A::MLLT3 and PML::RARA, indicating that lincRNA expression is responsive to oncogenic signaling. <b>Conclusions</b>: This comprehensive analysis shows that lincRNAs exhibit similar subclass-specific expression patterns as protein-coding genes and establishes a valuable resource for future studies on genetically defined AML subclasses, with potential implications for biomarker discovery and therapeutic targeting.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}