Search Results (3,062)

Bovine Viral Diarrhea Virus (BVDV) poses a significant threat to the global cattle industry, causing substantial economic losses. Long non-coding RNAs (lncRNAs) play crucial regulatory roles in various biological processes, including viral infections. However, the specific lncRNAs influencing BVDV replication remain poorly characterized. This study identified lncSMIM14 as a key host factor upregulated during BVDV infection in MDBK cells. Functional analyses demonstrated that lncSMIM14 overexpression significantly enhanced BVDV replication, evidenced by increased viral mRNA levels, progeny virus titers, cytopathic effects, and dsRNA abundance, while its knockdown exerted the opposite effect. Mechanistically, we revealed that lncSMIM14 specifically targets and positively regulates the expression of the endocytosis-related GTPase Rab3a. Importantly, Rab3a itself was shown to be essential for efficient BVDV replication, as its overexpression promoted viral replication, and its knockdown inhibited it. Furthermore, Rab3a co-localized with key endocytic regulators Rab5a and Rab7a, and both lncSMIM14 overexpression and Rab3a overexpression promoted the formation of endocytic vesicles, particularly post-BVDV infection. Our findings unveil a novel mechanism wherein BVDV exploits the host lncRNA lncSMIM14 to hijack Rab3a-mediated endocytosis, facilitating its own replication. This study identifies the lncSMIM14-Rab3a axis as a critical host pathway subverted by BVDV, providing new potential targets for antiviral intervention.: Full article

Renal cell carcinoma (RCC) represents the most frequent kidney malignancy and remains a major clinical challenge due to its often silent onset, high metastatic potential, and limited responsiveness to conventional chemotherapy. Increasing evidence indicates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are key regulators of RCC tumorigenesis, progression, and therapy resistance. Rather than providing a purely descriptive overview, this review focuses on emerging mechanistic paradigms through which ncRNAs actively shape tumor behavior and therapeutic response in RCC. This review summarizes current knowledge on the biological and clinical relevance of ncRNAs in RCC, highlighting their dual roles as oncogenic drivers or tumor suppressors through the modulation of pathways involved in proliferation, apoptosis, angiogenesis, invasion, immune evasion, metabolic reprogramming, and ferroptosis. Particular emphasis is placed on mechanistically defined ncRNA regulatory axes controlling ferroptosis, autophagy, metabolic reprogramming, and immune escape, as well as on ncRNA-mediated intercellular communication via extracellular vesicles, which promotes the dissemination of resistance to targeted therapies. The review also addresses ncRNA-based diagnostic and prognostic applications, including miRNA signatures capable of discriminating RCC subtypes and circulating ncRNAs as minimally invasive biomarkers. Moreover, the manuscript discusses ncRNA-mediated mechanisms of resistance to targeted therapies such as sunitinib, sorafenib, and axitinib, emphasizing regulatory networks involving miRNA targets, lncRNA–miRNA sponging, RNA-binding proteins, extracellular vesicle transfer, and epigenetic modulation. Emerging therapeutic opportunities are also addressed, including strategies aimed at inhibiting oncogenic ncRNAs or restoring tumor-suppressive ncRNAs to enhance drug sensitivity and improve patient stratification. Full article

Here we discuss three veterinary alphaherpesviruses—pseudorabies virus, equid alphaherpesvirus 1, and bovine alphaherpesvirus 1—that were instrumental in uncovering the true extent of transcriptome complexity through long-read RNA sequencing, which earlier short-read approaches could not resolve. We focus on three major transcriptomic features whose discovery and characterization relied heavily on these viral models: (i) widespread transcriptional overlaps that complicate read assignment and may drive transcriptional interference; (ii) diverse transcript isoforms arising from alternative 5′ and 3′ transcript termini, as well as splicing; and (iii) non-coding RNAs clustered near replication origins that illuminate potential replication–transcription interactions on a shared nuclear template. Long-read viromics in these veterinary systems has additionally served as a stringent benchmark for transcript callers and annotation pipelines, because the extreme density of overlaps and co-terminal transcript families exposes errors that often go unnoticed in typical mammalian transcriptomes. This has made veterinary herpesvirus datasets disproportionately influential in shaping best practices for full-length isoform calling, transcript end mapping, and artifact-robust cDNA library handling. We also discuss animal gammaherpesviruses as proxies for human gammaherpesviruses, allowing experimental investigation of viral programs difficult to study in human infection. Finally, we describe pseudorabies virus applications as a retrograde transneuronal tracer. Full article

Alzheimer’s disease (AD) is an aging-associated neurodegenerative disorder in which dysregulated neuroinflammation drives disease progression. Although long noncoding RNAs (lncRNAs) are increasingly implicated in AD, their mechanistic roles remain poorly defined. Here, we identified a novel lncRNA termed LIMASI (LncRNA Inflammation and Mucous associated, Antisense to ICAM1), that is linked with AD-associated neuroinflammation. LIMASI expression is significantly elevated in postmortem AD brain tissues and in a 3xTg-AD mouse model by qPCR and RNA fluorescence in situ hybridization, and its upregulation is correlated with increased β-amyloid plaque burden, tau hyperphosphorylation, and heightened neuroinflammatory activation. Cell type-specific analyses demonstrated inflammation-inducible LIMASI expression in astrocytes and microglia. In an in vitro model of AD-associated neuroinflammation, viral mimetic poly(I:C) challenge of amyloid precursor protein (APP)-overexpressing neuroblastoma cells elicited coordinated induction of LIMASI and key inflammatory mediators. Mechanistically, we observed elevated levels of inflammatory microRNAs (miR-155-5p and miR-150-5p) in AD brain tissues, and computational modeling predicted energetically favorable interactions between these miRNAs and LIMASI. These findings support a competing endogenous RNA (ceRNA) model in which LIMASI sequesters pro-inflammatory miRNAs to modulate neuroinflammatory gene networks. Together, our data identify LIMASI as a putative ceRNA strongly associated with AD-related neuroinflammation and suggest that targeting LIMASI may represent a novel strategy to attenuate neuroinflammatory signaling and potentially slow AD-associated neurodegeneration. Full article

Background: Long non-coding RNAs (lncRNAs) participate in a wide range of physiological processes, and their dysregulation is prevalent in human cancers, indicating critical roles in tumorigenesis. In intermediate- to high-risk gastrointestinal stromal tumors (GISTs), resistance to tyrosine kinase inhibitors (TKIs) remains a major therapeutic challenge. Therefore, identifying lncRNAs as potential novel therapeutic targets is of considerable interest. Methods: Three paired samples of intermediate- to high-risk GIST tissues and adjacent normal tissues were subjected to transcriptome sequencing. High-content screening (HCS) was subsequently performed to identify candidate lncRNAs with significant effects on GIST cell proliferation. Loss-of-function experiments were conducted, and cell proliferation, migration, and apoptosis were evaluated using the Cell Counting Kit-8 (CCK-8) assay, colony formation assay, Transwell migration assay, and flow cytometry, respectively. In addition, in situ hybridization (ISH) was performed on 507 primary GIST tissue specimens to examine the association between CTD-2245E15.3 expression and clinicopathological features, including progression-free survival (PFS) and overall survival (OS). Results: Transcriptome sequencing revealed 2924 upregulated and 2629 downregulated lncRNAs in GIST tissues compared with adjacent normal tissues. Based on HCS results, CTD-2245E15.3 was selected for further functional analyses. CCK-8 assays demonstrated that knockdown of CTD-2245E15.3 significantly inhibited proliferation of GIST cells. Consistently, colony formation and migratory capacity were markedly reduced in the shCTD-2245E15.3 group compared with controls. Furthermore, flow cytometric analysis showed a significant increase in apoptosis following CTD-2245E15.3 silencing. ISH analysis revealed that high CTD-2245E15.3 expression correlated with adverse clinicopathological features and poorer PFS and OS. Conclusions: Our study demonstrates that CTD-2245E15.3 promotes proliferation and migration of GIST cells and is associated with poor prognosis, highlighting its potential as a therapeutic target and diagnostic biomarker. Full article

Long non-coding RNAs (lncRNAs) encoded by viruses play crucial roles in viral infection, pathogenesis processes, the interaction between viruses and hosts, and immune escape. Herein, by employing RNA pull-down, mass spectrometry technology, and RNA immunoprecipitation, we identified a host protein (G3BP2) that specifically interacts with the lncRNA encoded by the infectious bronchitis virus (IBV). Additionally, we identified a novel host miRNA (novel-340) in IBV-infected H1299 cells and further verified that novel-340 can target the 3′-UTR (untranslated region) of G3BP2 and downregulate its expression in a dose-dependent manner. We discovered that IBV-lncRNA may facilitate IBV replication in H1299 cells through direct interaction with G3BP2 and/or the regulation of the IBV-lncRNA/novel-340/G3BP2 interactive regulatory network. This work deepens the understanding of the biological function of IBV-lncRNA. Full article

Background/Objectives: Acute myeloid leukemia is a genetically diverse hematological malignancy where patient outcomes vary significantly. Long non-coding RNA (lncRNA) GAS5 acts as a tumor suppressor and is frequently downregulated in various cancers, as well as in AML. In the current study, we aimed to explore the effects of GAS5 promoter variants on its expression levels in AML patients, their prognostic significance, and to investigate their functional effects. Methods: The GAS5 promoter region containing rs55829688 and rs145204276 was sequenced in 75 AML patients. Statistical analyses were performed to assess their associations with GAS5 expression and outcomes. An in vitro functional study in K562 cells evaluated the effects of these variants on the transcriptional activity of constructs containing each variant. In silico analysis was used to predict changes to transcription factor binding sites. Results: Patients carrying the rs55829688 TC/CC genotype exhibited lower GAS5 expression and were more frequently categorized into the adverse risk group. In intermediate-risk patients, this genotype trended toward lower overall survival and higher bone marrow blast percentages. In vitro, the construct harboring the rs55829688 C allele showed a two-fold decrease in reporter gene activity compared to the construct bearing both wild type alleles. In silico analysis identified RUNX3 as the most likely transcription factor affected by this variant. The variant rs145204276 was considered for the first time in AML; however, no significant clinical associations or transcriptional effects were found. Conclusions: Taken together, our findings provide evidence that the rs55829688 promoter variant reduces GAS5 expression in AML and could potentially be a prognostic marker. Full article

Soil salinity represents a significant abiotic constraint limiting the productivity and geographical expansion of rapeseed (Brassica napus L.), yet the coordination among the signaling, hormonal, metabolic, and regulatory layers underlying salt tolerance remains incompletely understood. This study elucidates the physiological, biochemical, and transcriptomic responses of B. napus inbred line 383-5 to moderate salt stress (100 mM NaCl at day 10), identifying key lncRNA–mRNA regulatory networks. Salt stress induced pronounced, dose-dependent growth inhibition, oxidative damage, and osmotic adjustment, accompanied by extensive transcriptional reprogramming. Genome-wide analyses identified 6215 differentially expressed protein-coding genes and 941 salt-responsive long non-coding RNAs (lncRNAs), revealing coordinated regulation of ion transport, redox homeostasis, phytohormone signaling, and secondary metabolism. Functional enrichment analyses highlighted the central involvement of abscisic acid and ethylene signaling pathways, MAPK cascades, membrane transporters, and antioxidant systems. Notably, salt stress strongly activated the phenylpropanoid and lignin biosynthesis pathways, suggesting reinforced cell wall remodeling and enhanced oxidative stress mitigation. Integration of lncRNA–mRNA regulatory networks further indicated that non-coding transcripts act as important modulators linking hormone signaling, redox balance, and metabolic adaptation. Collectively, these results reveal a multilayered and tightly synchronized regulatory framework underlying salinity tolerance in B. napus and provide valuable molecular targets for the genetic improvement of salt-resilient rapeseed cultivars. Full article

Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy characterized by frequent recurrence and metastasis, which poses a significant global health problem. One of the prominent hallmarks of cancer is glucose metabolic reprogramming, wherein glycolysis is preferred over oxidative phosphorylation for macromolecule biosynthesis and energy production, even in the presence of oxygen. Non-coding RNAs (ncRNAs) are defined as a class of RNAs that are not translated into proteins, which include microRNAs, long non-coding RNAs, and circular RNAs. Recent studies have found that ncRNAs are crucial in regulating glycolysis in OSCC, wherein they reshape the metabolic landscape by modulating the expression of glucose transporters, essential enzymes, and transcription factors, ultimately influencing tumorigenesis. This comprehensive review systematically summarizes the regulatory mechanisms of ncRNAs involved in glucose metabolic reprogramming in OSCC, evaluates their potential as diagnostic biomarkers and therapeutic targets, and identifies clinically relevant ncRNAs through an integrative analysis of patient-derived data. These insights provide a mechanistic understanding of the metabolic alterations that drive progression in OSCC, as well as knowledge that can facilitate the development of clinically translatable targeted interventions for this aggressive malignancy. Full article

Early detection of hepatocellular carcinoma (HCC) remains challenging due to limitations including the lack of reliable biomarkers. While molecular diagnostics hold promise, their use is limited because tissue biopsies are not routinely performed in HCC. Long non-coding RNAs (lncRNA), such as HOXA transcript at the distal tip (HOTTIP), have been implicated in HCC, with single-nucleotide polymorphisms forming haplotypes that may influence disease progression. This study investigated the clinical relevance of HOTTIP SNPs rs17501292 and rs2067087 in 198 Egyptian HCC patients (129 non-metastatic, 69 metastatic). Moreover, molecular docking was used to design small interfering RNAs (siRNAs) targeting HOTTIP. Genotypes TT and TG (rs17501292) and GG and GC (rs2067087) were associated with reduced metastatic risk compared to GG and CC genotypes, respectively. Survival analysis revealed that TT (rs17501292) and GC (rs2067087) genotypes correlated with improved outcomes. ROC curve analysis confirmed the diagnostic and prognostic value of specific genetic models, affirming their value as biomarkers for metastasis and survival. Molecular docking identified two promising therapeutic candidates. Overall, we can conclude that HOTTIP SNPs may serve as promising potential non-invasive biomarkers for HCC metastasis and prognosis, while the identified siRNAs offer a novel targeted therapeutic approach. Full article

LINC01270 is a long intergenic noncoding RNA implicated in the progression of various cancers. In our previous study, we demonstrated that LINC01270 plays a role in regulating the pro-inflammatory response in the THP-1 monocytic cell line, partly through modulation of NF-κB activation. Given the multifaceted nature of inflammation and the ability of noncoding RNAs to influence this process at multiple levels, we further investigated the potential role of LINC01270 in modulating additional inflammatory signaling pathways in lipopolysaccharide (LPS)-stimulated THP-1 cells. We found that attenuation of LINC01270 levels led to increased transcription and phosphorylation of STAT1, accompanied by elevated expression of the genes under STAT1 regulation. Further investigation revealed that LINC01270 regulates STAT1 expression via the miR-326/leucine zipper downregulated in cancer 1 (LDOC1) axis. Notably, inhibition of the interaction between LINC01270 and miR-326 effectively reversed the effects of LINC01270 knockdown on STAT1 expression and its downstream targets. Interestingly, both gain- and loss-of-function experiments with LDOC1 resulted in a consistent upregulation of STAT1 transcription. Taken together, our findings highlight a pleiotropic role of the LINC01270 in regulating the pro-inflammatory response through modulation of STAT1 signaling, in addition to its previously established role in NF-κB regulation. Furthermore, this study uncovers a novel function of the LDOC1 in inflammation through its regulation of STAT1. These findings provide new mechanistic insights into lncRNA–microRNA–protein interactions in inflammatory signaling and may open avenues for developing novel therapeutic strategies targeting chronic inflammatory diseases. Full article

Cibotium barometz (L.) J. Sm., a medicinally significant fern in traditional Chinese medicine, is little explored at the genomic level regarding its bioactive compounds. Using an integrated approach combining Illumina and PacBio sequencing technologies, we profiled its root, rachis, and pinna transcriptomes, identifying 12,718, 21,341, and 11,441 unigenes, respectively. Our analysis systematically characterized the transcriptional features of transcription factors (TFs), simple sequence repeats (SSRs), long non-coding RNAs (lncRNAs), and differentially expressed genes (DEGs). Enrichment analyses highlighted the roles of highly expressed unigenes in secondary metabolism. Seventeen key enzymes involved in polysaccharide biosynthesis showed tissue-specific expression patterns. Notably, total polysaccharide content correlated positively with UDP-arabinose 4-epimerase (UXE) expression but negatively with phosphoglucomutase (PGM) and 3,5-epimerase/4-reductase (UER1). Flavonoid accumulation inversely correlated with chalcone synthase (CHS) expression. Two lignin pathways (H-lignin and G-lignin) were characterized, with phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), and cinnamyl alcohol dehydrogenase (CAD) as key genes. The absence of ferulate-5-hydroxylase (F5H) explains the undetected S-lignin pathway. Regulatory network analysis revealed positive correlations between PAL expression and NAC72/NAC78/WRKY35 and C4H expression and WRKY65/WRKY69/WRKY71, while a negative correlation was revealed between flavonoid 3′,5′-hydroxylase (F3′5′H) and MYB3R4. This study provides comprehensive transcriptomic insights into C. barometz bioactive compound biosynthesis, serving as a foundation for mechanistic research. Full article

Ovarian follicular development determines the egg-laying performance in chickens. Besides hormonal signaling, epigenetic and post-transcriptional regulators, long non-coding RNAs (lncRNAs) also play a vital role in follicular development. We previously identified that RAR-related orphan receptor B-intronic transcript 1 (RORB-IT1), a novel lncRNA located in the intron of RORB, was differentially expressed in chicken pre-hierarchical and hierarchical follicular granulosa cells (Post-GCs). However, it remains unknown whether RORB-IT1 participates in regulating the development of chicken ovarian follicles. In this study, we further characterized the expression pattern of RORB-IT1 and explored its role in regulating the progesterone synthesis, proliferation and apoptosis of chicken Post-GCs. The results showed that RORB-IT1, with a full length of 383 bp, exhibits a uniform distribution in both the cytoplasm and nucleus of chicken Post-GCs. RORB-IT1 was specifically expressed in Post-GCs and upregulated by follicle-stimulating hormone (FSH), progesterone (P4) and estradiol (E2) in a dose-dependent manner. Functionally, RORB-IT1 promoted P4 synthesis and proliferation, while inhibiting the apoptosis of Post-GCs. Furthermore, we demonstrated that RORB-IT1 encoded a functional micropeptide exhibiting dual localization in both cytoplasmic and nuclear compartments. This micropeptide enhanced progesterone synthesis and proliferation, but paradoxically induced the apoptosis of Post-GCs when overexpressed independently. Collectively, this study uncovered the expression pattern and function of RORB-IT1 in chicken Post-GCs and provided a theoretical basis for improving the egg-laying performance in chickens. Full article

Hepatoblastoma is the predominant primary liver malignancy in children, and outcomes remain poor for patients with metastatic disease. Long non-coding RNAs (lncRNAs) regulate tumor behavior, but their role in metastatic hepatoblastoma is not well defined. This study investigates the expression and functional significance of the lncRNA, maternally expressed gene 3 (MEG3), in a metastatic hepatoblastoma model. RNA sequencing comparing the metastatic hepatoblastoma cell line, HLM_2, with its parental HuH6 cell line identified MEG3 as being significantly upregulated in metastatic cells. MEG3 expression was examined using hepatoblastoma patient datasets and validated using qPCR in cell lines, orthotopic tumors, and COA67 patient-derived xenografts. The effects of siRNA MEG3 knockdown in HLM_2 cells on clonogenicity, migration, and invasion were evaluated. The effects of MEG3 overexpression on migration and invasion were assessed in HuH6 cells. MEG3 was significantly upregulated in metastatic cells and orthotopic tumors compared with controls. MEG3 silencing reduced clonogenicity, tumorsphere formation, migration, and invasion. MEG3 overexpression increased migration and invasion. These findings indicate that MEG3 contributes to an aggressive tumor phenotype, highlighting the need for further examination into its mechanistic role in hepatoblastoma and its potential as a biomarker or therapeutic target. Full article

Mitochondrial dysfunction plays a major role in diabetic retinopathy development and in its resistance to halt after the reversal of hyperglycemia (metabolic memory). Diabetes also upregulates many long noncoding RNAs, RNAs with >200 nucleotides with no reading frame, and several of them resist reversal after hyperglycemia cessation. Our aim was to investigate the role of LncRNA HOTAIR, a master regulator of chromatin dynamics, in mitochondrial biogenesis in diabetic retinopathy and in metabolic memory. Using retinal endothelial cells and Müller cells, incubated in high glucose (20 mM D-glucose), the effect of HOTAIR-siRNA on mitochondrial biogenesis was investigated by quantifying mitochondrial mass, copy numbers, and mtDNA replication, structure, and function. HOTAIR’s role in metabolic memory was investigated by analyzing mitochondrial biogenesis in HOTAIR-siRNA transfected cells incubated in high glucose for four days, followed by normal glucose (5 mM D-glucose) for four days. HOTAIR was upregulated in both retinal vascular and nonvascular cells, and HOTAIR-siRNA ameliorated decreases in mtDNA biogenesis and protected their mitochondria from structural/functional damage. Reversal of high glucose insult failed to ameliorate HOTAIR upregulation and impaired mtDNA biogenesis in both endothelial and Müller cells, but regulation of HOTAIR during high glucose incubation, which followed normal glucose, prevented a decrease in mitochondrial mass and mtDNA copies. Thus, HOTAIR has a major role in mitochondrial biogenesis and in the continued impaired biogenesis in both vascular and nonvascular cells. Regulating HOTAIR may provide a therapeutic option to inhibit the development/progression of diabetic retinopathy. Full article