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Results for “long non-coding RNAs (lncRNAs)”

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PubMed2026

Adaptation to Plant Defence in an Agricultural Insect Pest: Integrating Genome Scans and Gene Expression in the Soybean Aphid Reveals Multi-Genic Pathways.

In agroecosystems, intense selection pressures cause species to adapt and spread, often leading to the evolution and persistence of pests. Understanding how pests rapidly adapt can help develop sustainable strategies for their management and improve agroecosystem health. Pest adaptation involves stable variations in DNA sequence, as well as dynamic shifts in gene expression, often mediated by non-coding regulatory elements. We examined adaptation to plant defences in the soybean aphid, Aphis glycines, in which virulent aphids have overcome plant defences and avirulent aphids have not. Previous data with laboratory colonies suggested that virulent aphids have higher overall gene expression, including transposable elements, some of which influence gene regulation. However, we lack information on how genetic variation in natural populations impacts adaptation and potentially gene regulation. We integrated population genome scans of field-collected, soybean aphid populations with gene expression profiles of virulent and avirulent laboratory colonies to uncover connections between genetic differentiation and gene regulation for virulence. Genome scan methods found 2144 single nucleotide polymorphisms (SNPs) with significant genetic differentiation (i.e., outliers) in field-collected populations. These SNPs were near 1004 genes, representing 5.16% of the effective number of genes. Based on previous RNA-Seq data with laboratory colonies, we found 3160 genes and 147 long non-coding RNAs (lncRNAs) with differential expression among virulent and avirulent biotypes. By integrating both data sets, we identified 16 genes and 5 long non-coding RNAs with differential expression and that were associated with an outlier SNP (within 10 kbp). We validated SNPs with additional field collected aphids and found an aphid clone with stronger virulence than our laboratory virulent colony, surviving on 2 different aphid-resistant soybean varieties. This new virulent clone had fixed allele differences at 9 SNPs compared to our avirulent and other virulent colony. Field collected soybean aphids matching the phenotype of this new virulent clone had significant genetic differentiation with 3 outlier SNPs near genes related to zinc transport and lachesin compared to field collected avirulent aphids. Our entire data reinforced the importance of a potential multi-genetic response to overcome plant defence and generates new insights into complex genetic and regulatory mechanisms involved in insect-plant interactions.

Animals↗

PubMed2025

Constructing epigenetic regulatory landscapes of plant lncRNAs-an exploration utilizing the novel specialized platform PERlncDB.

Long non-coding RNAs (lncRNAs), once overlooked as transcriptional byproducts, are now recognized for their crucial roles in plant growth, development, and stress responses, with increasing focus on their epigenetic regulation. However, studies investigating epigenomic signals to explore the functions of lncRNAs in plants remain relatively limited. This study collected a comprehensive dataset of over 160 000 high-quality lncRNAs from 19 representative plant species and integrated 6715 ChIP-seq, BS-seq, and RNA-seq datasets to analyze epigenomic patterns at lncRNA loci. Results showed elevated DNA methylation in lncRNA regions. The highest levels occurred in transposable element-associated lncRNAs. Additionally, activating histone modifications at lncRNA loci showed tissue specificity, with epigenetic preferences differed from those at protein-coding gene (PCG) loci. Differential site analysis in epigenetic mutants further highlighted the selective regulation of lncRNA loci by specific epigenetic factors. To facilitate research, we developed PERlncDB, a platform that provides species-specific lncRNA browsing, epigenetic annotation, cross-species conservation analysis, and visualization of epigenomic landscapes. Case studies on MARS and LINC-AP2 emphasized the platform's utility. Conserved epigenetic mechanisms regulating lncRNAs across species, exemplified by a syntenic conserved MET1-regulated lncRNA pair in Arabidopsis and tomato, suggested the stability of regulatory mechanisms underlying lncRNA functions. This work provides critical insights and resources for understanding plant lncRNA epigenetic regulation.

RNA, Long Noncoding↗

PubMed2026

Micropeptides encoded by lncRNAs associated with cancer progression reveal novel immunogenic epitopes.

MOTIVATION: Long non-coding RNAs (lncRNAs) regulate gene expression, chromatin organization, and cellular signaling. Recent studies indicate that ∼20% of the ∼36 000 human lncRNA genes harbor small open reading frames (sORFs) capable of producing micropeptides (MPs), whose functions remain largely unknown. Whether these peptides contribute to the cancer immunopeptidome is largely unexplored. RESULTS: We systematically analyzed lncRNAs with strong experimental and computational evidence of MP-encoding potential (∼13% of the initial MP collection). Using The Cancer Genome Atlas (TCGA), we identified 2606 high-confidence lncRNA-derived MPs encoded by 647 genes across 16 cancer types. We then focused on 501 MPs from 124 lncRNA genes whose expression changes significantly across tumor stages and metastatic transitions, representing cancer transitional lncRNAs (Tr-lncRNAs). Dipeptide composition and conservation analyses showed that these MPs differ from a size-matched human coding proteome, supporting their potential as neoantigens. All possible 9-mer peptides were evaluated for predicted binding to prevalent European HLA class I alleles. Approximately 60% of Tr-lncRNA genes and 184 (37%) of derived peptides exhibited strong predicted HLA binding. Peptides from XIST, PCAT7, PVT1, HAND2-AS1 showed broad HLA coverage. Notably, TTN-AS1, encoded an MP (79 aa) generated 33 predicted distinct epitopes spanning all 27 HLA alleles. Our analysis identifies lncRNA-derived MPs as a previously underexplored source of potential cancer neoantigens, highlighting their promise as biomarkers and targets for immunotherapy. AVAILABILITY: Data, code and supplementary materials are available in https://doi.org/10.5281/zenodo.20167452 and GitHub: https://github.com/stavzok1/lncrna_peptide_analysis.

Humans↗

PubMed2026

Identifying Co-Expressed lncRNAs Correlated With Traits of Interest in an Animal Model for Metabolic Diseases in Humans.

Nutrigenomics investigates how nutrients modulate gene expression. Among them, fatty acids (FA) play important roles in regulating gene transcription, while long non-coding RNAs (lncRNAs) may be associated with gene regulation and metabolic diseases. This study aimed to analyze the hepatic transcriptome of pigs, a species frequently used as a model for nutrigenomic studies, to identify novel lncRNAs and their potential target genes in response to diets containing different sources of FA. Seventy-two pigs were fed four diets supplemented with 1.5% soybean oil (control), 3% canola oil, 3% fish oil, and 3% soybean oil. RNA sequencing of liver samples was performed to identify novel lncRNAs. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify modules associated with phenotypic traits related to lipid metabolism and inflammation. Functional enrichment analyses were then conducted to annotate genes within these modules using Gene Ontology (GO) terms and to assess overlap with Quantitative Trait Loci (QTL). The results revealed 106 novel lncRNAs potentially regulating genes associated with lipid metabolism and immune responses in pigs fed diets with different FA sources. These findings enhance understanding of the regulatory role of lncRNAs in pigs and reinforce their relevance as models for human metabolic diseases.

Animals↗

PubMed2026

EGFR-co-amplified lncRNA ELDR drives glioblastoma tumorigenicity by enhancing BMI1 activity.

BACKGROUND: In glioblastoma (GBM), epidermal growth factor receptor (EGFR) amplification, one of the most prevalent genetic alterations, often occurs on extrachromosomal DNAs (ecDNAs) that contain amplified oncogenes and regulatory elements, driving tumor progression. Despite the central oncogenic role of EGFR amplification, therapeutic strategies targeting EGFR have demonstrated limited clinical efficacy, suggesting that additional mechanisms may underlie EGFR-driven GBM malignancy and treatment resistance. Long non-coding RNAs (lncRNAs) are critical regulators in cancer; however, the roles of EGFR-associated lncRNAs-particularly those localized on ecDNA-in GBM tumorigenicity and therapeutic resistance remain poorly understood. METHODS: Transcriptomic and genomic analyses were performed to identify lncRNAs co-amplified with EGFR. Biochemical and molecular biological studies were carried out to reveal the mechanisms. In vivo xenograft models were used to evaluate the tumorigenicity and the therapeutic efficacy of combination treatment strategies. RESULTS: The lncRNA EGFR long non-coding downstream RNA (ELDR) was co-amplified with EGFR on ecDNA and chromosomes and was associated with poor prognosis in glioma. ELDR promoted GBM tumorigenicity through a BMI1-dependent epigenetic mechanism operating in parallel with canonical EGFR signaling. Mechanistically, ELDR interacted with purine-rich element-binding protein A (PURA), disrupted the inhibitory PURA-BMI1 interaction, and thereby enhanced the activity of BMI1, a core component of Polycomb repressive complex 1 (PRC1). Therapeutically, combining a BMI1 inhibitor or ELDR-targeting antisense oligonucleotides (ASOs) with an EGFR inhibitor erlotinib significantly enhanced antitumor efficacy in preclinical models of  EGFR  -amplified GBM with high ELDR expression. CONCLUSION: EGFR co-amplified ELDR promotes GBM tumorigenicity by enhancing BMI1 activity. Targeting the ELDR-BMI1 axis in combination with EGFR inhibition represents a promising therapeutic strategy for a subset of  EGFR  -amplified GBMs with high ELDR expression.

EGFR↗

PubMed2024

Transcriptome-wide N6-methyladenosine modification profiling of long non-coding RNAs in patients with recurrent implantation failure.

N6-methyladenosine (m6A) is involved in most biological processes and actively participates in the regulation of reproduction. According to recent research, long non-coding RNAs (lncRNAs) and their m6A modifications are involved in reproductive diseases. In the present study, using m6A-modified RNA immunoprecipitation sequencing (m6A-seq), we established the m6A methylation transcription profiles in patients with recurrent implantation failure (RIF) for the first time. There were 1443 significantly upregulated m6A peaks and 425 significantly downregulated m6A peaks in RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that genes associated with differentially methylated lncRNAs are involved in the p53 signalling pathway and amino acid metabolism. The competing endogenous RNA network revealed a regulatory relationship between lncRNAs, microRNAs and messenger RNAs. We verified the m6A methylation abundances of lncRNAs by using m6A-RNA immunoprecipitation (MeRIP)-real-time polymerase chain reaction. This study lays a foundation for further exploration of the potential role of m6A modification in the pathogenesis of RIF.

Humans↗

PubMed2026

The identification of growth-promoting lncRNAs in oral cavity squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma (OCSCC) is an aggressive tumor that develops within the mouth of patients. Tumor-suppressor gene loss and genomic arrangements fuel tumorigenesis and transcriptional reprogramming. Understanding how these alterations contribute to OCSCC growth and cell survival may identify new therapeutic vulnerabilities or biomarkers. We profiled the role of long non-coding RNAs (lncRNAs) in the growth of three OCSCC cell lines using a CRISPRi-screen and identified 19 lncRNAs that contribute to OCSCC proliferation. By comparing these lncRNAs to other screens, we find that these lncRNAs are uniquely required in OCSCC and not other malignancies. We show that these lncRNAs are abundantly expressed in OCSCC cells and tumors. Independent testing of candidate lncRNAs confirms their role in supporting OCSCC growth. Our results show that a novel subset of lncRNAs are required for the growth of OCSCC cancer cells and that these lncRNAs are cell lineage specific.

CRISPRi↗

PubMed2026

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals↗

PubMed2025

Genome imbalance modulates the expression of long non-coding RNAs in maize.

Genome imbalance, resulting from varying the dosage of individual chromosomes (aneuploidy), has a more detrimental effect than changes in complete sets of chromosomes (haploidy/polyploidy). This imbalance is likely due to disruptions in stoichiometry and interactions among macromolecular assemblies. Previous research has shown that aneuploidy causes global modulation of protein-coding genes (PCGs), microRNAs, and transposable elements (TEs), affecting both the varied chromosome (cis-located) and unvaried genome regions (trans-located) across various taxa. While long non-coding RNAs (lncRNAs) are important gene expression regulators, their roles in the context of genomic imbalance remain largely unexplored. In this study, we analyzed and compared the impact of aneuploidy and haploidy/polyploidy on lncRNA expression using RNA-seq data from maize mature leaf tissue. Our results indicate that cis-located lncRNAs are modulated from dosage compensation to a gene dosage effect, while trans-located lncRNAs exhibit trends ranging from an inverse effect to a positive correlation with chromosomal dosage. Remarkably, the ploidy series showed a lesser degree of lncRNA modulation. LncRNAs and TEs display a similar trend of inverse modulation but exhibit greater sensitivity to dosage changes compared to PCGs. The construction of cis-acting and trans-acting lncRNA co-expression networks indicates that lncRNAs likely function as dosage-sensitive regulators of gene expression under conditions of genomic imbalance. Overall, this study not only elucidates the dosage effect of plant lncRNAs but also serves as a valuable resource for exploring potential regulators of PCGs that play significant biological functions.

Zea mays↗

PubMed2026

A novel deep learning-driven framework for improving lncRNA comprehensive annotation with LncADeep 2.0.

MOTIVATION: Long non-coding RNAs (lncRNAs) have emerged as crucial players in diverse physiological and pathological processes, yet the biological mechanisms of the vast majority of lncRNAs remain elusive. To fill this gap, it is necessary to improve the accuracy of lncRNA identification and functional annotation. RESULTS: Here, we introduce LncADeep 2.0, an integrated deep learning framework designed to meet these needs. In the identification module, LncADeep 2.0 incorporated novel peptide features along with sequence and structural information, demonstrating superior performance over our previous LncADeep and other existing tools on both annotated transcripts from GENCODE and RNA-seq data. For functional annotation, LncADeep 2.0 leveraged lncRNA-centric interaction networks and gene ontology terms through the transfer learning strategy to achieve robust annotation performance with limited functional data. Compared to LncADeep, LncADeep 2.0 could accurately elucidate the general functions of given lncRNA sequences, predict tissue- or cell-type-specific functions from bulk and single-cell RNA-seq data, and establish connections between tumor-associated lncRNAs and genomic markers. Overall, LncADeep 2.0 stands out as an efficient and reliable tool for lncRNA identification and functional annotation across a wide spectrum of biological processes. AVAILABILITY AND IMPLEMENTATION: LncADeep 2.0 is available for use at https://github.com/Jefferson-Chou/LncADeep2 and https://doi.org/10.5281/zenodo.17164767.

RNA, Long Noncoding↗

PubMed2026

Long non-coding RNAs link DNA methylation to immune regulatory networks in bovine subclinical mastitis.

Long non-coding RNAs (lncRNAs) are emerging as important regulators of inflammatory and immune signaling, yet their contribution to bovine subclinical mastitis remains poorly defined. Here, we characterized the lncRNA expression landscape associated with disease in milk somatic cells of healthy and subclinical mastitic Vrindavani cattle. We identified 11,403 high-confidence lncRNAs, of which 104 were differentially expressed in subclinical mastitis (adjusted P < 0.05; |log2FC| ≥ 1), with the vast majority upregulated in mastitic samples. Predicted cis- and trans-associated target analyses identified 637 non-redundant genes, and KEGG analysis identified 8 significantly enriched cis-associated pathways and 152 significantly enriched trans-associated pathways (adjusted P < 0.05), predominantly enriched for immune and inflammation-related pathways. These findings prioritized a subset of mastitis-associated lncRNAs for subsequent methylation and interaction-network analyses. A subset of these lncRNAs further overlapped differentially methylated regions (DMRs), suggesting a potential association between lncRNA expression changes and DNA methylation alterations. Integration of lncRNA-miRNA and miRNA-mRNA interactions identified lncRNA-miRNA-mRNA interaction networks involving DMR-associated lncRNAs. Among the prioritized candidates, MSTRG.28878.1 showed overlap with a hypomethylated promoter-associated DMR, increased expression, and multiple connections within the predicted interaction network. Together, these findings identify candidate lncRNAs, methylation-associated loci, and predicted molecular interactions associated with bovine subclinical mastitis and provide a resource for future functional investigation of candidate non-coding RNA-associated mechanisms in disease.

Animals↗

PubMed2026

Comparative transcriptome analysis of Qinchuan and Wagyu cattle reveals lnc11599 as a negative regulator of intramuscular fat deposition.

BACKGROUND: Intramuscular fat (IMF) content is a critical factor determining beef quality, influenced by various factors including breed and age. However, the regulatory role of long non-coding RNAs (lncRNAs) in IMF deposition remains unclear. METHODS: This study investigated IMF deposition in the longissimus dorsi muscle of one- and two-year-old Qinchuan and Wagyu cattle through histological examination and fat content measurement. Based on transcriptome sequencing data of intramuscular fat tissue, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify lncRNAs associated with IMF deposition. The effects of a key candidate lncRNA on the adipogenic differentiation of cattle intramuscular preadipocytes were further examined. RESULTS: Results showed that Wagyu cattle exhibited stronger IMF deposition capacity than Qinchuan cattle across all age groups, with IMF content increasing with age in both breeds. We identified 7,910 lncRNAs from intramuscular fat tissue transcriptome data, including 6,455 novel lncRNAs. Through integrated differential expression analysis and WGCNA, 88 lncRNAs closely associated with IMF deposition were screened from two-year-old Qinchuan and Wagyu cattle. Notably, lnc11599 was significantly upregulated in Qinchuan cattle intramuscular fat tissue, but its expression decreased during intramuscular preadipocyte differentiation. Functional experiments demonstrated that lnc11599 knockdown enhanced adipogenic differentiation capacity, manifested as a highly significant increase in lipid accumulation, upregulation of key adipogenic genes at the mRNA level, together with increases in total fatty acid content and unsaturated fatty acid proportion. CONCLUSIONS: This study established the lncRNA expression profiles in intramuscular fat tissue of Qinchuan and Wagyu cattle across different developmental stages, and demonstrated that lnc11599 acts as a negative regulator of intramuscular fat deposition. These findings provide new directions for elucidating the mechanisms of cattle IMF deposition and offer potential targets for genetic improvement of beef quality.

Animals↗

PubMed2026

Context-dependent effects of MIR100HG on tumorigenic phenotypes and p38/MAPK-AKT signaling in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide and is characterized by a hypoxic tumor microenvironment that promotes tumor progression, cellular adaptation, and therapeutic resistance. Increasing evidence indicates that long non-coding RNAs (lncRNAs) play critical roles in regulating tumor-associated signaling networks; however, the contribution of MIR100HG to hepatocellular carcinoma progression, particularly under hypoxic conditions, remains insufficiently understood. In this study, we investigated the expression pattern and functional significance of MIR100HG in hepatocellular carcinoma using epithelial-like Hep3B and mesenchymal-like SNU-398 cells, together with non-tumor hepatocytes (Clone-9). Gain- and loss-of-function approaches were employed to evaluate the impact of MIR100HG on tumor-associated cellular phenotypes under both normoxic and hypoxic conditions. Functional assays demonstrated that MIR100HG overexpression significantly enhanced cell proliferation, clonogenic potential, migration, and invasion, whereas MIR100HG silencing markedly suppressed these tumorigenic properties and increased apoptotic cell death. Mechanistic analyses revealed that MIR100HG promotes oncogenic signaling through the p38/MAPK and AKT pathways under normoxic conditions, whereas MIR100HG depletion reduced the phosphorylation of these key signaling proteins. Notably, additional pathway analyses under hypoxia-mimicking conditions revealed a distinct signaling response, in which the MIR100HG-associated activation of p38/MAPK and AKT observed under normoxia was not maintained. Moreover, the expression patterns of AKT-associated regulatory genes, including GAS6 and PTEN, were reversed under hypoxia-mimicking conditions. These findings suggest that the effects of MIR100HG on oncogenic signaling are highly dependent on the cellular oxygenation context and that hypoxia reshapes the downstream signaling consequences of MIR100HG expression in HCC cells. Collectively, our findings identify MIR100HG as a hypoxia-associated oncogenic regulator that enhances tumorigenic phenotypes and promotes survival signaling in hepatocellular carcinoma. These results highlight MIR100HG as a potential biomarker and therapeutic target in liver cancer and provide new insights into the molecular mechanisms underlying hypoxia-driven tumor progression.

Humans↗

PubMed2026

The regulatory role of non-coding RNAs in taxane resistance of breast cancer.

Breast cancer remains a major health concern among women, characterized by a high risk and substantial mortality. Chemotherapy is widely employed as a standard treatment modality to eliminate malignant cells and improve patient survival. Nevertheless, recurrence and chemoresistance arising from taxane treatment have emerged as key factors driving the high mortality rates in cancer patients. Non-coding RNAs (ncRNAs), encompassing microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), represent a key functional output of the human genome and, via intricate regulatory networks, influence nearly all facets of cancer biology, including the development of chemoresistance. Importantly, in taxane-resistant breast cancer cells, the identified miRNAs displayed bifunctional roles: some promoted resistance, whereas others enhanced sensitivity. This functional duality is also observed in lncRNAs, highlighting their context‑dependent regulatory roles. Additionally, ncRNAs are enriched in taxane-resistant cells-derived exosomes, where they play a crucial role in spreading taxane resistance and chemotherapy failure through genetic modulation of taxane‑sensitive cells. Notably, targeting ncRNAs via various therapeutic approaches, including herbal compounds and synthetic peptides, has shown hopeful findings in reversing taxane resistance in breast cancer, highlighting a promising avenue for the management of taxane resistance in breast cancer.

Breast cancer↗

PubMed2026

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans↗

PubMed2024

Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells.

Genomes produce widespread long non-coding RNAs (lncRNAs) of largely unknown functions. We characterize aal1 (ageing-associated lncRNA), which is induced in quiescent fission yeast cells. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression prolongs their lifespan, indicating that aal1 acts in trans. Overexpression of aal1 represses ribosomal-protein gene expression and inhibits cell growth, and aal1 genetically interacts with coding genes functioning in protein translation. The aal1 lncRNA localizes to the cytoplasm and associates with ribosomes. Notably, aal1 overexpression decreases the cellular ribosome content and inhibits protein translation. The aal1 lncRNA binds to the rpl1901 mRNA, encoding a ribosomal protein. The rpl1901 levels are reduced ~2-fold by aal1, which is sufficient to extend lifespan. Remarkably, the expression of the aal1 lncRNA in Drosophila boosts fly lifespan. We propose that aal1 reduces the ribosome content by decreasing Rpl1901 levels, thus attenuating the translational capacity and promoting longevity. Although aal1 is not conserved, its effect in flies suggests that animals feature related mechanisms that modulate ageing, based on the conserved translational machinery.

RNA, Long Noncoding↗

PubMed2026

Transcriptome changes in circulating immune cells of critical COVID-19 patients predict a specific metabolic and epigenetic imprint.

BACKGROUND: The progression to critical COVID-19 arises predominantly from a dysregulated host immune response although the underlying regulatory mechanisms still remain partially elusive. This limits a prompt prediction of the disease progression, reduces the therapeutic options and restrains our understanding of “long COVID”. METHODS: Here, we analyzed the transcriptome of peripheral blood mononuclear cells (PBMCs) collected from COVID-19 patients experiencing different degrees of the disease (mild and critical), and control patients enrolled in the clinical trial COntAGIouS as well as independent bulk RNA-seq, single-cell RNA-seq and proteomic datasets. RESULTS: In critical COVID-19 patients, the integrative analysis of transcriptomic data revealed an altered regulatory network involving microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and coding genes that control mRNA translation-related genes, epigenetics, and metabolism. In parallel, we observed an upregulation of tRNA aminoacylation genes in critical COVID-19 patients by the analysis of either bulk or single-cell RNA-seq data from publicly available independent cohorts. Additionally, we found increased expression of coding genes enriched for the cognate amino acids (glycine, alanine, isoleucine and tyrosine), all related to protein localization, post-translational modifications, and cell metabolism in our cohort. Similar alterations in amino acid frequency were found in an independent proteomic dataset. CONCLUSIONS: Collectively, our findings indicate a broad perturbation of the gene expression landscape that characterizes the aberrant host immune response in critical COVID-19 patients and is potentially coordinated by miRNA and tRNA metabolism alterations. TRIAL REGISTRATION: COntAGIouS, NCT04327570. Registered 26 March 2020, https://clinicaltrials.gov/ct2/show/NCT04327570 .

Female↗

PubMed2026

Non-coding RNAs in cancer: multi-omics insights, liquid biopsy advances, drug resistance mechanisms, and the road to clinical translation.

For most of the twentieth century, the transcriptional output of the human genome was thought to be biologically inert-a characterization that has been proven wrong in almost every important respect. Non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), small nucleolar RNAs (snoRNAs) and PIWI-interacting RNAs (piRNAs) are now thought of as vital regulators of gene expression in all the stages of cancer pathogenesis, including the initial epigenetic changes, metastatic spread and the development of therapeutic resistance. This review highlights four areas where the clinical potential of ncRNAs is most promising: reconstruction of ncRNA regulatory networks by multi-omics integration; circulating ncRNAs as minimally invasive cancer biomarkers; causal roles of ncRNAs in drug resistance through epithelial-mesenchymal plasticity, metabolic reprogramming, and stromal communication; and translation of ncRNA targeting strategies to clinical trials. We will need to invest equally in mechanistic rigor and translational infrastructure to move forward.

antisense oligonucleotides↗