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Long non-coding RNAs (lncRNAs) have begun to receive overdue attention for their regulatory roles in gene expression and other cellular processes. Although most lncRNAs are lowly expressed and tissue-specific, notable exceptions include MALAT1 and its genomic neighbor NEAT1, two highly and ubiquitously expressed oncogenes with roles in transcriptional regulation and RNA splicing. Previous studies have suggested that NEAT1 is found only in mammals, while MALAT1 is present in all gnathostomes (jawed vertebrates) except birds. Here we show that these assertions are incomplete, likely due to the challenges associated with properly identifying these two lncRNAs. Using phylogenetic analysis and structure-aware annotation of publicly available genomic and RNA-seq coverage data, we show that NEAT1 is a common feature of tetrapod genomes except birds and squamates. Conversely, we identify MALAT1 in representative species of all major gnathostome clades, including birds. Our in-depth examination of MALAT1, NEAT1, and their genomic context in a wide range of vertebrate species allows us to reconstruct the series of events that led to the formation of the locus containing these genes in taxa from cartilaginous fish to mammals. This evolutionary history includes the independent loss of NEAT1 in birds and squamates, since NEAT1 is found in the closest living relatives of both clades (crocodilians and tuataras, respectively). These data clarify the origins and relationships of MALAT1 and NEAT1 and highlight an opportunity to study the change and continuity in lncRNA structure and function over deep evolutionary time.

BACKGROUND: It has been shown that long non-coding RNA (lncRNA) plays an important role in the development and progression of cardiac diseases, and whether it is involved in daisy leaf gentianone antagonizing adriamycin-induced cardiac injury in mice has not been reported. OBJECTIVE: To screen differentially expressed lncRNAs in myocardial tissue of mice with adriamycin-induced myocardial injury antagonized with daisy leaf gentianone and conduct a bioinformatics analysis. METHODS: Forty-eight C57 mice were randomly divided into normal group, model group, daisy leaf gentianone group and positive drug group, with 12 mice in each group. The mice in the model group, daisy leaf gentianone group and positive drug group were injected with adriamycin intraperitoneally once every other day for 8 times in total. The daisy leaf gentianone group and positive drug group were given daisy leaf gentianone suspension and captopril solution by gavage based on adriamycin injection once a day for 21 continuous days. After medication, mice in each group underwent electrocardiogram examination and the myocardial tissue was taken for pathomorphological observation. At the same time, high-throughput sequencing analysis of mouse myocardial tissue was carried out, differentially expressed lncRNAs were screened, and target genes were predicted for differentially expressed lncRNAs. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses of target genes were performed. RESULTS AND CONCLUSION: The ST segment of the electrocardiogram of mice in the model group was significantly elevated. Compared with the model group, the degree of ST-segment elevation on the electrocardiogram was reduced in the daisy leaf gentianone group. Results from hematoxylin-eosin, Masson, and Sirius red staining indicated that in the model group, the myocardial cytoplasm was unevenly colored with varying shades of color, the integrity and continuity of myocardial fibers were poor, and a large number of collagen fibers were deposited. After treatment with gentianone daisy leaves, the abnormalities in myocardial tissue of mice were improved. The results of high-throughput sequencing analysis showed that compared with the model group, a total of 270 lncRNAs were identified in the myocardial tissue of mice in the daisy leaf gentianone group, including 165 up-regulated and 105 down-regulated lncRNAs. Combining the experimental results with related literature, three lncRNAs (NONMMUT149833.1, NONMMUT003237.2, and ENSMUST00000219015) and four related mRNAs (Alas2, Igf2, Acta1, and Cilp) were finally identified. The results of target gene prediction, gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses showed that differentially expressed lncRNAs in myocardial tissue of mice with myocardial injury could regulate the expression of their target protein-coding genes through cis- and/or trans-regulation, and participate in regulating molecular functions and biological processes. To conclude, daisy leaf gentianone significantly improves cardiac function and partial lncRNA expression in mice with adriamycin-induced myocardial injury. [ABSTRACT FROM AUTHOR]

Background: Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. Methods: Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. Results: The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM − receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. Conclusions: Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC. [ABSTRACT FROM AUTHOR]

SUMMARY Long non‐coding RNAs (lncRNAs) play crucial roles in various biological processes in plants. However, the functional mechanism of lncRNAs in fruit ripening, particularly the transition from unripe to ripe stages, remains elusive. One such lncRNA1840, reported by our group, was found to have important role in tomato fruit ripening. In the present study, we gain insight into its functional role in fruit ripening. CRISPR‐Cas9 mediated lncRNA1840 mutants caused the delayed tomato fruit ripening. Notably, loss function of lncRNA1840 did not directly impact ethylene signaling but rather delay ethylene synthesis. Transcriptomic analysis revealed differences in the expression of ripening related genes in lncRNA1840 mutants, suggesting that it is involved in gene regulation of fruit ripening. We used Chromatin Isolation by RNA Purification (ChIRP)‐Seq to identify lncRNA1840 binding sites on chromatin. ChIRP‐seq suggested that lncRNA1840 had occupancy on 40 genes, but none of them is differentially expressed genes in transcriptomic analysis, which indicated lncRNA1840 might indirectly modulate the gene expression. ChIRP‐mass spectrometry analysis identified potential protein interactors of lncRNA1840, Pre‐mRNA processing splicing factor 8, highlighting its involvement in post‐transcriptional regulatory pathways. In summary, lncRNA1840 is key player in tomato plant growth and fruit ripening, with multifaceted roles in gene expression and regulatory networks. [ABSTRACT FROM AUTHOR]

Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes acute and chronic peripheral sensory neuropathy, for which no effective treatment has been established. In particular, chronic neuropathy can persist for years even after treatment completion, thus worsening patients' quality of life. To avoid the development of intractable adverse effects, a predictive biomarker early in treatment is awaited. In this study, we explored extracellular long non-coding RNAs (lncRNAs) released from primary sensory neurons as biomarker candidates for oxaliplatin-induced peripheral neuropathy. Because many human-specific lncRNA genes exist, we induced peripheral sensory neurons from human induced pluripotent stem cells. Oxaliplatin treatment changed the levels of many lncRNAs in extracellular vesicles (EVs) released from cultured primary sensory neurons. Among them, the levels of release of lncRNAs that were considered to be selectively expressed in dorsal root ganglia were correlated with those of lncRNAs in plasma EV obtained from healthy individuals. Several lncRNAs in plasma EVs early after the initiation of treatment showed greater changes in patients who did not develop chronic neuropathy that persisted for more than 1 year than in those who did. Therefore, these extracellular lncRNAs in plasma EVs may represent predictive biomarkers for the development of chronic peripheral neuropathy induced by oxaliplatin. [ABSTRACT FROM AUTHOR]

Recently, numerous studies including various tissues have been carried out on long non-coding RNAs (lncRNAs), but still, its variability has not yet been fully understood. In this study, we characterised the inter-individual variability of lncRNAs in pigs, in the context of number, length and expression. Transcriptomes collected from muscle tissue belonging to six Polish Landrace boars (PL1–PL6), including half-brothers (PL1–PL3), were investigated using bioinformatics (lncRNA identification and functional analysis) and statistical (lncRNA variability) methods. The number of lncRNA ranged from 1289 to 3500 per animal, and the total number of common lncRNAs among all boars was 232. The number, length and expression of lncRNAs significantly varied between individuals, and no consistent pattern has been found between pairs of half-brothers. In detail, PL5 exhibits lower expression than the others, while PL4 has significantly higher expression than PL2–PL3 and PL5–PL6. Noteworthy, comparing the inter-individual variability of lncRNA and mRNA expression, they exhibited concordant patterns. The enrichment analysis for common lncRNA target genes determined a variety of biological processes that play fundamental roles in cell biology, and they were mostly related to whole-body homeostasis maintenance, energy and protein synthesis as well as dynamics of multiple nucleoprotein complexes. The high variability of lncRNA landscape in the porcine genome has been revealed in this study. The inter-individual differences have been found in the context of three aspects: the number, length and expression of lncRNAs, which contribute to a better understanding of its complex nature. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are versatile RNA molecules recently identified as key regulators of gene expression in response to environmental stress. Our primary focus in this study was to develop a robust computational pipeline for identifying structurally identical lncRNAs across replicates from publicly available bulk RNA-seq datasets. In order to demonstrate the effectiveness of the pipeline, we utilized the transcriptome of the thermophilic fungus Thermothelomyces thermophilus and assessed the expression pattern of lncRNAs in conjunction with Heat Shock Proteins (HSP), a well-known protein family critical for the cell's response to high temperatures. Our findings demonstrate that the identification of structurally identical transcripts among replicates in this thermophilic fungus ensures the reliability and accuracy of RNA studies, contributing to the validity of biological interpretations. Furthermore, the majority of lncRNAs exhibited a distinct expression pattern compared to HSPs. Our study contributes to advancing the understanding of the biological mechanisms comprising lncRNAs in thermophilic fungi. [ABSTRACT FROM AUTHOR]

Background: There is an association between obesity and psychological disorders such as depression, anxiety, and stress. Environmental factors and genetics play a crucial role in this regard. Several long non-coding RNAs (lncRNAs) are involved in the pathophysiology of the nervous system. Additionally, we intend to investigate how dietary glycemic index and load relate to psychological disorders in women with obesity and overweight by identifying the possible interaction with metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1). Methods: 267 overweight or obese women between the ages of 18 and 48 were recruited for the current study. A reliable and validated food frequency questionnaire (FFQ) consisting of 147 items assessed food consumption, glycemic load (GL), and glycemic index (GI). Depression-Anxiety-Stress Scales (DASS-21) were used to assess mental well-being. A real-time polymerase chain reaction (PCR) was used to assess transcript levels for lncRNAs MALAT1 and TUG1. Results: In obese and overweight women, a positive correlation was found between anxiety and MALAT1 mRNA levels (P = 0.007, CC = 0.178). Age, energy intake, physical activity, total fat, income, marriage, thyroid, and BMI were adjusted, and GI and TUG1 were positively correlated on DASS-21 (β = 0.006, CI = 0.001, 0.01, P = 0.031), depression (β = 0.002, CI = 0.001, 0.004, P = 0.019), Stress (β = 0.003, CI = 0.001, 0.005, P = 0.027). The interaction of GL and TUG1 on stress was also observed (β = 0.03, CI = 0.001, 0.07, P = 0.048). Conclusions: The lncRNA TUG1 appears to be associated with depression and stress through interaction with GI and correlated with stress by interaction with GL. To establish this concept, further research is required. [ABSTRACT FROM AUTHOR]

Background: Plant long non-coding RNAs (lncRNAs) have important regulatory roles in responses to various biotic and abiotic stresses, including light quality. However, no lncRNAs have been specifically linked to the Shade Avoidance Response (SAS). Results: To better understand the involvement of lncRNAs in shade avoidance, we examined RNA-seq libraries for lncRNAs with the potential to function in the neighbor proximity phenomenon in Arabidopsis thaliana (A. thaliana). Using transcriptomes generated from seedlings exposed to high and low red/far-red (R/FR) light conditions, we identified 13 lncRNA genes differentially expressed in cotyledons and 138 in hypocotyls. To infer possible functions for these lncRNAs, we used a 'guilt-by-association' approach to identify genes co-expressed with lncRNAs in a weighted gene co-expression network. Of 34 co-expression modules, 10 showed biological functions related to differential growth. We identified three potential lncRNAs co-regulated with genes related to SAS. T-DNA insertions in two of these lncRNAs were correlated with morphological differences in seedling responses to increased FR light, supporting our strategy for computational identification of lncRNAs involved in SAS. Conclusions: Using a computational approach, we identified multiple lncRNAs in Arabidopsis involved in SAS. T-DNA insertions caused altered phenotypes under low R/FR light, suggesting functional roles in shade avoidance. Further experiments are needed to determine the specific mechanisms of these lncRNAs in SAS. [ABSTRACT FROM AUTHOR]

AbstractGlioblastoma multiforme (GBM) is an aggressive and diffuse type of glioma with the lowest survival rate in patients. The recent failure of multiple treatments suggests that targeting several targets at once may be a different strategy to overcome GBM carcinogenesis. Normal function of oncogenes and tumor suppressor genes need for the preservation of regular cellular processes, so any defects in these genes’ activity, operate the corresponding signaling pathways, which initiate carcinogenic processes. Long non-coding RNAs (lncRNAs) that can be found in the cytoplasm or nucleus of the cells, control the transcription and translation of genes. LncRNAs perform a variety of functions, including epigenetic alteration, protein modification and stability, transcriptional regulation, and competition for miRNA that regulate mRNA translation through sponging miRNAs. Identification of various oncogenic lncRNAs and their multiple roles in brain cancers making them potential candidates for use as glioma diagnostic, prognostic, and therapeutic targets in the future. This study highlighted multiple oncogenic lncRNAs and classified them into different signaling pathways based on the regulated target genes in glioblastoma. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and are implicated in neurodegenerative diseases, including frontotemporal dementia (FTD). However, their expression patterns and potential as biomarkers in genetic FTD involving Chromosome 9 Open Reading Frame (C9ORF72), Microtubule Associated Protein Tau (MAPT), and Progranulin (GRN) genes are not well understood. Objective: This study aimed to profile the expression levels of lncRNAs in peripheral blood mononuclear cells collected within the GENetic Frontotemporal dementia Initiative (GENFI). Methods: Fifty-three lncRNAs were analyzed with the OpenArray Custom panel, in 131 patients with mutations in C9ORF72, MAPT, and GRN, including 68 symptomatic mutation carriers (SMC) and 63 presymptomatic mutation carriers (PMC), compared with 40 non-carrier controls (NC). Results: Thirty-eight lncRNAs were detectable; the relative expression of NEAT1 and NORAD was significantly higher in C9ORF72 SMC as compared with NC. GAS5 expression was instead significantly lower in the GRN group versus NC. MAPT carriers showed no significant deregulations. No significant differences were observed in PMC. Disease duration did not correlate with lncRNA expression. Conclusions: NEAT1 and NORAD are upregulated in C9ORF72 SMC and GAS5 levels are downregulated in GRN SMC, underlining lncRNAs' relevance in FTD and their potential for biomarker development. Further validation and mechanistic studies are crucial for clinical implications. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs), once considered transcriptional noise, have emerged as critical regulators of gene expression and key players in cancer biology. Recent breakthroughs have revealed that certain lncRNAs can encode small open reading frame (sORF)-derived peptides, which are now understood to contribute to the pathogenesis of various cancers. This review synthesizes current knowledge on the detection, functional roles, and clinical implications of lncRNA-encoded peptides in cancer. We discuss technological advancements in the detection and validation of sORFs, including ribosome profiling and mass spectrometry, which have facilitated the discovery of these peptides. The functional roles of lncRNA-encoded peptides in cancer processes such as gene transcription, translation regulation, signal transduction, and metabolic reprogramming are explored in various types of cancer. The clinical potential of these peptides is highlighted, with a focus on their utility as diagnostic biomarkers, prognostic indicators, and therapeutic targets. The challenges and future directions in translating these findings into clinical practice are also discussed, including the need for large-scale validation, development of sensitive detection methods, and optimization of peptide stability and delivery. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are endogenous non-coding RNAs that play significant roles in the chemoresistance mechanisms of colorectal cancer (CRC). Chemotherapy is a crucial treatment modality for CRC, but resistance to chemotherapy remains a major challenge. Various studies have demonstrated that lncRNAs contribute to CRC chemoresistance through different mechanisms. Consequently, targeting lncRNAs to overcome CRC chemoresistance has been proposed as a therapeutic strategy. This review summarizes the recent advances in research on the mechanisms by which lncRNAs contribute to chemoresistance in CRC. [ABSTRACT FROM AUTHOR]

Temperature is an important environmental factor affecting heading date of rice. Despite its importance, genes responsible for temperature-sensitive heading in rice have remained elusive. Our previous study identified a quantitative trait locus qHd1 which advances heading date under high temperatures. A 9.5-kb insertion was found in the first intron of OsMADS51 in indica variety Zhenshan 97 (ZS97). However, the function of this natural variant in controlling temperature sensitivity has not been verified. In this study, we used CRISPR/Cas9 to knock out the 9.5-kb insertion in ZS97. Experiments conducted under cotrolled conditions in phytotrons confirmed that deletion increased temperature sensitivity and advanced heading by downregulating the expression level of OsMADS51. One-hybrid assays in yeast, ChIP-quantitative polymerase chain reaction, electrophoretic mobility shift, and luciferase-based transient transactivation assays collectively confirmed that OsMADS51 affects heading date by regulation of heading date gene Ehd1. We further determined that the long non-coding RNA HEATINR is generated from the first intron of OsMADS51, offering an explanation for how the 9.5-kb insertion affects temperature sensitivity. We also found that OsMADS51 was strongly selected in early/late-season rice varieties in South China, possibly accounting for their strong temperature sensitivity. These insights not only advance our understanding of the molecular mechanisms underlying the temperature-responsive regulation of heading date in rice but also provide a valuable genetic target for molecular breeding. [ABSTRACT FROM AUTHOR]

Cardiac mesoderm enhancer-associated non-coding RNA (CARMN), an evolutionarily conserved long non-coding RNA (lncRNA), serves as the host gene for the miR143/145 cluster. It plays a crucial role in cardiovascular cell differentiation and the maintenance of vascular smooth muscle cell (VSMC) homeostasis, which are vital for normal physiological processes. Specifically, CARMN is associated with the pathological progression of cardiovascular diseases such as atherosclerosis, abdominal aortic aneurysm, and chronic heart failure. Moreover, it acts as a tumor suppressor in various cancers, including hepatocellular carcinoma, bladder cancer, and breast cancer, highlighting its potential as a beneficial biomarker and therapeutic target. This review provides a detailed examination of the roles of CARMN, its evolutionary conservation, expression patterns, and regulatory mechanisms. It also outlines its significant implications in the diagnosis, prognosis, and treatment of these diseases, underscoring the need for further translational research to exploit its clinical potential. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease that arises as a multi-stage process involving multiple cell types. Patients diagnosed with the same clinical stage and pathological classification may have different prognoses and therapeutic responses due to alterations in molecular genetics. As an essential marker for the molecular subtyping of breast cancer, long non-coding RNAs (lncRNAs) play a crucial role in gene expression regulation, cell differentiation, and the maintenance of genomic stability. Here, we developed a modular framework for lncRNA identification and applied it to a breast cancer cohort to identify novel lncRNAs not previously annotated. To investigate the potential biological function, regulatory mechanisms, and clinical relevance of the novel lncRNAs, we elucidated the genomic and chromatin features of these lncRNAs, along with the associated protein-coding genes and putative enhancers involved in the breast cancer regulatory networks. Furthermore, we uncovered that the expression patterns of novel and annotated lncRNAs identified in breast cancer were related to the hormone response in the PAM50 subtyping criterion, as well as the immune response and progression states of breast cancer across different immune cells and immune checkpoint genes. Collectively, the comprehensive identification and functional analysis of lncRNAs revealed that these lncRNAs play an essential role in breast cancer by altering gene expression and participating in the regulatory networks, contributing to a better insight into breast cancer heterogeneity and potential avenues for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Transposable elements (TEs) are major components of eukaryotic genomes. The extensive body of evidence suggests that although they were once considered "genomic parasites", transposons and their transcripts perform specific functions, such as regulation of early embryo development. Understanding the role of TEs in such parasites as trematodes is becoming critically important. Fasciola hepatica, a parasite affecting humans and livestock, undergoes a complex life cycle in diverse environments and hosts, and knowledge about its life cycle regulation is scarce so far. Methods: We summarized the data regarding the repetitive elements in F. hepatica and conducted bulk RNA-seq analysis across its life cycle stages. TE expression profiles were analyzed, focusing on differential expression and potential homology with previously described long non-coding RNAs (lncRNAs). Results: Differential expression analysis revealed stage-specific TE transcription patterns, notably peaking during egg and metacercariae stages. Some TEs showed homology with known lncRNAs and contained putative transcription factor binding sites. Interestingly, TE transcription levels were highest in eggs and metacercariae compared to adults, suggesting regulatory roles in trematode life cycle transitions. Conclusions: These findings suggest that TEs may play roles in regulating trematode life cycle transitions. Moreover, TE homology with lncRNAs underscores their significance in gene regulation. [ABSTRACT FROM AUTHOR]

Aim: Cu2O nanoparticles were synthesized using an extract from S. latifolium algae (SLCu2O NPs). Their effect on PANC-1 cells and the expression of two drug resistance-related lncRNAs were evaluated in comparison with Arsenic trioxide. Materials & methods: SLCu2O NPs were characterized using XRD, SEM, and TEM microscopies. The effects of SLCu2O NPs on cell cytotoxicity, cell cycle, and apoptosis, and expression of two drug resistance-related lncRNAs were examined using MTT assay, flow cytometry, and real-time PCR, respectively. Results: SLCu2O NPs demonstrated anti-cancer properties against PANC-1 cells comparable to Arsenic trioxide, and the expression of lncRNAs increased upon treatment with them. Conclusion: SLCu2O NPs demonstrate anti-cancer properties against PANC-1 cells; however, using gene silencing strategies along with SLCu2O NPs is suggested. Article highlights Copper nanoparticles have been proposed as a novel anti-cancer agent in cancer research including Pancreatic cancer. Copper oxide nanoparticles synthesis via physicochemical routs restricted their use in further cancer research or future clinical applications due to using highly toxic chemicals, high energy consumption, and high cost of synthesis. In this study, Cu2O nanoparticles were synthesized using an extract from S. latifolium algae to address environmental concerns. The XRD patterns of the S. latifolium-derived Cu2O nanoparticles showed the prominent peaks attributed to planes (110), (111), (200), (220), (311), and (222) that confirm the formation of the single-phase cubic structure with Pn-3m space group. Scanning electron microscopy confirm the spherical-cubic shape of S. latifolium-derived Cu2O nanoparticles with the average size of 40–50 nm. S. latifolium-derived Cu2O nanoparticles induced cell cytotoxicity on PANC-1 cells with IC50 of 72.75 and 65.4 μg/ml at 24 and 48 h, respectively. S. latifolium-derived Cu2O nanoparticles induced S-phase cell cycle arrest and apoptosis in PANC-1 cells. S. latifolium-derived Cu2O nanoparticles showed comparable effects to arsenic trioxide in terms of cell cytotoxicity, colony formation, cell cycle arrest, and apoptosis. S. latifolium-derived Cu2O nanoparticles increased the expression of two drug-resistant related lncRNAs, HOTAIR and HOTTIP, which may suggest using gene silencing strategies along with these nanoparticles. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative pathology whose pathognomonic hallmarks are increased generation of β-amyloid (Aβ) peptide, production of hyperphosphorylated (pTau), and neuroinflammation. The last is an alteration closely related to the progression of AD and although it is present in multiple neurodegenerative diseases, the pathophysiological events that characterize neuroinflammatory processes vary depending on the disease. In this article, we focus on mRNA and non-coding RNA alterations as part of the pathophysiological events characteristic of neuroinflammation in AD and the influence of these alterations on the course of the disease through interaction with multiple RNAs related to the generation of Aβ, pTau, and neuroinflammation itself. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear. Results: Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells. Conclusions: Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients. [ABSTRACT FROM AUTHOR]

Background: To investigate the role of lncRNA LINC00665 in modulating ovarian cancer stemness and its influence on treatment resistance and cancer development. Methods: We isolated ovarian cancer stem cells (OCSCs) from the COC1 cell line using a combination of chemotherapeutic agents and growth factors, and verified their stemness through western blotting and immunofluorescence for stem cell markers. Employing bioinformatics, we identified lncRNAs associated with ovarian cancer, with a focus on LINC00665 and its interaction with the CNBP mRNA. In situ hybridization, immunohistochemistry, and qPCR were utilized to examine their expression and localization, alongside functional assays to determine the effects of LINC00665 on CNBP. Results: LINC00665 employs its Alu elements to interact with the 3'-UTR of CNBP mRNA, targeting it for degradation. This molecular crosstalk enhances stemness by promoting the STAU1-mediated decay of CNBP mRNA, thereby modulating the Wnt and Notch signaling cascades that are pivotal for maintaining CSC characteristics and driving tumor progression. These mechanistic insights were corroborated by a series of in vitro assays and validated in vivo using tumor xenograft models. Furthermore, we established a positive correlation between elevated CNBP levels and increased disease-free survival in patients with ovarian cancer, underscoring the prognostic value of CNBP in this context. Conclusions: lncRNA LINC00665 enhances stemness in ovarian cancer by mediating the degradation of CNBP mRNA, thereby identifying LINC00665 as a potential therapeutic target to counteract drug resistance and tumor recurrence associated with CSCs. [ABSTRACT FROM AUTHOR]

Background: The escalating prevalence of metabolic diseases has led to a rapid increase in non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (NASH-HCC). While oxaliplatin (OXA)-based hepatic arterial infusion chemotherapy (HAIC) has shown promise in advanced-stage HCC patients, its efficacy in NASH-HCC remains uncertain. This study aims to assess the effectiveness of OXA-based HAIC and elucidate the mechanisms underlying OXA resistance in NASH-HCC. Methods: The key lncRNAs were screened through RNA-seq analysis of NASH/non-NASH and OXA-sensitive/OXA-resistant (OXA-S/R) HCC tissues. The biological functions of the lnc-OXAR (OXA resistance–related lncRNA in NASH-HCC) in NASH-HCC were verified through a series of in vitro and in vivo experiments. The molecular mechanism of lnc-OXAR was elucidated by fluorescence in situ hybridization, immunoprecipitation-mass spectrometry (FISH), Immunoprecipitation-Mass Spectrometry (IP-MS), RNA pulldown, RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and a dual-luciferase reporter assay. Results: NASH-HCC exhibited reduced responsiveness to OXA-based HAIC compared to non-NASH HCC. We identified and validated a novel transcript namedlnc-OXAR, which played a crucial role in conferring OXA resistance to NASH-HCC. Inhibition of lnc-OXAR suppressed HCC cell growth and restored OXA sensitivity both in NASH-HCC mouse models and in vitro. Mechanistically, lnc-OXAR recruited Ku70 and cystatin A (CSTA), preventing Ku70 degradation and facilitating DNA double-strand break (DSB) repair, thereby promoting OXA resistance in NASH-HCC. Additionally, WTAP-mediated m6A modification enhanced the stability of lnc-OXAR in an IGF2BP2-dependent manner. Notably, silencing lnc-OXAR significantly enhanced the response to OXA in patient-derived xenograft (PDX) models derived from NASH-HCC. Conclusions: The reduced responsiveness of NASH-HCC to OXA treatment can be attributed to the upregulation of lnc-OXAR. Our findings provide a rationale for stratifying HCC patients undergoing OXA-based HAIC based on etiology. Lnc-OXAR holds promise as a novel target for overcoming OXA resistance in NASH-HCC and improving prognosis. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) play various roles in gene regulation. GATA3 antisense RNA 1 (GATA3-AS1) is an lncRNA gene neighboring GATA binding protein 3 (GATA3). The current study aims to quantitatively compare the levels of the expression of GATA3-AS1, GATA3, and Interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) samples of MS patients and healthy individuals under the hypothesis of regulation of GATA3 and IL-4 expression orchestrated by GATA3-AS1. Methods and results: In this case-control study, the GATA3-AS1, GATA3 and IL-4 expression profiles were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Also, we assessed the IL-4 levels in the serum. The median fold changes in MS patients vs. controls were (4.39 ± 0.38 vs. 2.44 ± 0.20) for GATA3-AS1, (5.22 ± 0.51 vs. 2.86 ± 0.30) for GATA3, and (6.16 ± 0.52 vs. 3.57 ± 0.38) for IL-4, (P < 0.001). Furthermore, the mean serum levels of IL-4 were 30.85 ± 1.53 pg/ml in MS patients and 11.15 ± 4.23 pg/ml in healthy controls (P < 0.001). ROC curve analysis showed that the level of GATA3-AS1 might serve as a biomarker for diagnosing MS patients with the area under the curve (AUC = 0.918, P < 0.0001). Based on our results, this GATA3-AS1/GATA3/IL-4 pathway may increase IL-4 expression in MS patients. Conclusions: Our results indicate a probably regulatory function for GATA3-AS1and the levels of GATA3-AS1 in blood could be important biomarkers for MS diagnosis. To confirm and be more certain of these results, it is necessary to study neuromyelitis optica (NMO) and asthma patients in future studies. [ABSTRACT FROM AUTHOR]

The lack of diagnostic markers limits the window of effectiveness for rheumatoid arthritis (RA) therapies. Here, we isolated exosomes of serum samples from four distinct groups RA patients, according to disease activity and with/without medication. Then, total RNA of exosomes was extracted for wholetranscriptome sequencing. Focusing on lncRNA sequencing, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed. We found that the number of upregulated lncRNAs were significantly higher than that of downregulated lncRNAs in each four RA groups. And most importantly, we identified two specific lncRNAs from differentially expressed lncRNAs, TCONS_;I2_;00013502 (up-regulated) and ENST00000363624 (down-regulated) in RA. Receiver Operating Characteristic (ROC) curve analysis showed that the two lncRNAs were promising biomarkers for RA diagnosis. These findings highlight lncRNAs of the serum exosome are important biomarkers and provide application potential for diagnosis of RA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Long non-coding RNAs (lncRNAs), as important regulators of the inflammatory response, are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE: To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways, pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS: PubMed was searched using the search terms of “ischemic stroke, long non-coding RNA, neuroinflammation, immune function, signal pathway, microglia, astrocytes, oligodendrocyte, mechanism,” and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION: In the early stage of ischemic stroke, the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain, promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses. As an important pathogenesis factor in ischemic stroke, the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke, and it needs to be suppressed promptly in the early stage. Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia, astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects. LncRNAs, as important regulatory factors of the inflammatory response, inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB, lncRNA-miRNA-mRNA axis, Rho-ROCK, MAPK, AKT, ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke. Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model, but no clinical trials have been conducted. Therefore, it remains to be further explored about whether lncRNAs can be safely applied in clinical practice. At present, there are many therapeutic drugs for the treatment of ischemic stroke, but there are relatively few studies on the application of lncRNAs, exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology, which need to be further explored. lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity. In future studies, more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored, in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is the most common form of dementia. Currently, there is no single test that can diagnose AD, especially in understudied populations and developing countries. Instead, diagnosis is based on a combination of medical history, physical examination, cognitive testing, and brain imaging. Exosomes are extracellular nanovesicles, primarily composed of RNA, that participate in physiological processes related to AD pathogenesis such as cell proliferation, immune response, and neuronal and cardiovascular function. However, the identification and understanding of the potential role of long non-coding RNAs (lncRNAs) in AD diagnosis remain largely unexplored. Here, we clinically, cognitively, and genetically characterized a sample of 15 individuals diagnosed with AD (cases) and 15 controls from Barranquilla, Colombia. Advanced bioinformatics, analytics and Machine Learning (ML) techniques were used to identify lncRNAs differentially expressed between cases and controls. The expression of 28,909 lncRNAs was quantified. Of these, 18 were found to be differentially expressed and harbored in pivotal genes related to AD. Two lncRNAs, ENST00000608936 and ENST00000433747, show promise as diagnostic markers for AD, with ML models achieving > 95% sensitivity, specificity, and accuracy in both the training and testing datasets. These findings suggest that the expression profiles of lncRNAs could significantly contribute to advancing personalized AD diagnosis in this community, offering promising avenues for early detection and follow-up. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of long non-coding RNA (lncRNA) -AFAP1-AS1 and microRNA (miR) -195-5p on the biological behavior of hepatocellular carcinoma (HCC) cells. Methods Human HCC cell lines (HepG2, Hep3B, SMMC-7721, Bel7402, SK-hep1 cells) and normal human liver cells (HL-7702 cells) were routinely cultured. The expression levels of AFAP1-AS1 and miR-195-5p were detected by real-time fluorescence quantitative PCR to select the experimental cells. The experimental cells in logarithmic growth phase were randomly assigned to different groups： si-AFAP1-AS1 group, si-NC group, miR-195-5p mimics group, mimics-NC group, miR-195-5p inhibitor+si-NC group, miR-195-5p inhibitor+si-AFAP1-AS1 group, inhibitor-NC+si-AFAP1-AS1 group, and inhibitor-NC+si-NC group, respectively. Subsequently, the corresponding plasmids were transfected into the cells using Lipofectamine 2000 reagent based on the grouping. Cell proliferation was assessed by CCK-8 and colony formation experiments, while apoptosis and cell cycle were analyzed using flow cytometry. Cell migration and invasion capabilities were evaluated by Transwell experi­ment, and the targeted relationship between AFAP1-AS1 and miR-195-5p was confirmed via dual luciferase reporter gene assay. Results In HCC cells, AFAP1-AS1 expression was higher than that in normal liver cells (P<0. 05), while miR195-5p expression was lower than that of the normal liver cells (P<0. 05) . Given that SK-hep1 cells exhibited the highest AFAP1-AS1 expression and the lowest miR-195-5p expression, subsequent investigations were carried out using SK-hep1 cells for experimental purposes. Compared with the si-NC group, the si-AFAP1-AS1 group displayed reduced AFAP1-AS1 expression, decreased cell proliferation capacity, reduced migration and invasion cells, a higher cell population in the G0/ G1 phase, and an elevated apoptosis rate (all P<0. 05) . The Starbase v3. 0 online database predicted that there were complementary binding sites between AFAP1-AS1 and miR-195-5p. Findings from the dual-luciferase reporter gene assay indicated that there was significant difference in the relative luciferase activity between the miR-NC and miR-195-5p after cotransfection of WT-AFAP1-AS1 (P<0. 05), while no significant difference was found after co-transfection of MUT-AFAP1- AS1 (P>0. 05) . Compared with the inhibitor-NC+si-NC group, the si-NC+miR-195-5p inhibitor group demonstrated enhanced cell proliferation, increased migration and invasion, reduced cell population in the G0/G1 phase, and decreased apoptosis rate (all P<0. 05) . Conversely, the si-AFAP1-AS1+miR-195-5p inhibitor group exhibited the opposite cellular responses. Conclusion The lncRNA AFAP1-AS1 potentially plays a role in regulating various biological processes in HCC cells, including proliferation, migration, invasion, and apoptosis, through its competitive interaction with miR-195-5p. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression alterations of long non-coding RNA (LncRNA) long intergenic non-coding RNA 00342（LINC00342), and microRNA-596（miR-596) in the gastric cancer tissues and their relationships with the clinicopathological parameters and prognosis. Methods Ninety-three gastric cancer patients were selected, and we obtained the gastric cancer tissues and adjacent cancer tissues in the surgery. Real-time fluorescence quantitative PCR was used to detect the expression levels of LncRNA LINC00342 and miR-596. The binding sites of LncRNA LINC00342 and miR-596 were predicted by starBase database, and the correlation between the expression of LncRNA LINC00342 and miR-596 in gastric cancer tissues was analyzed by Pearson correlation. The relationship between the expression levels of LncRNA LINC00342 and miR-596 in gastric cancer tissues and clinical pathological parameters was analyzed. The gastric cancer patients were followed up after surgery. Gastric cancer tissues were divided into high/low expression groups according to the mean values of LncRNA LINC00342 and miR-596, and the 3-year survival rates of patients with high/low expression of LncRNA LINC00342 and miR-596 were plotted using the Kaplan-Meier method. Cox regression model was used to analyze the influence of the expression levels of LncRNA LINC00342 and miR-596 on the prognosis of gastric cancer patients. Results Compared with the adjacent tissues, the expression of LncRNA LINC00342 was higher and the expression of miR-596 was lower in the gastric cancer tissues (both P<0. 05) . The starBase database predicted that there was a complementary sequence between LncRNA LINC00342 and the 3' untranslated end of miR-596, and the expression of LncRNA LINC00342 and miR-596 was negatively correlated in gastric cancer tissues (r＝－0. 777，P<0. 05) . LncRNA LINC00342 and miR-596 expression levels were associated with the degree of differentiation, TNM stage and lymph node metastasis of gastric cancer (all P<0. 05) . Thirty-six out of 93 gastric cancer patients died, and the 3-year overall survival rate was 61. 29% (57/93) . Compared with patients with high expression of LncRNA LINC00342, the 3-year overall survival rate of gastric cancer patients with low expression of LncRNA LINC00342 was higher (P<0. 05) . Compared with patients with low expression of miR-596, the 3-year overall survival rate of gastric cancer patients with high expression of miR-596 was higher (P<0. 05) . Low differentiation, TNM stage III, lymph node metastasis, and LncRNA LINC00342 ≥ 1. 52 were the independent risk factors for the prognosis of gastric cancer patients (all P<0. 05), and miR-596 ≥ 0. 82 was the independent protective factor (P<0. 05) . Conclusion LncRNA LINC00342 is highly expressed and miR-596 is low expressed in the gastric cancer tissues, and the expression changes of both are related to the degree of tissue differentiation, TNM staging, lymph node metastasis, and prognosis. [ABSTRACT FROM AUTHOR]

Poplar coma, the fluff-like appendages of seeds originating from the differentiated surface cells of the placenta and funicle, aids in the long-distance dispersal of seeds in the spring. However, it also poses hazards to human safety and causes pollution in the surrounding environment. Unraveling the regulatory mechanisms governing the initiation and development of coma is essential for addressing this issue comprehensively. In this study, strand-specific RNA-seq was conducted at three distinct stages of coma development, revealing 1888 lncRNAs and 52,810 mRNAs. The expression profiles of lncRNAs and mRNAs during coma development were analyzed. Subsequently, potential target genes of lncRNAs were predicted through co-localization and co-expression analyses. Integrating various types of sequencing data, lncRNA-miRNA-TF regulatory networks related to the initiation of coma were constructed. Utilizing identified differentially expressed genes encoding kinesin and actin, lncRNA-miRNA-mRNA regulatory networks associated with the construction and arrangement of the coma cytoskeleton were established. Additionally, relying on differentially expressed genes encoding cellulose synthase, sucrose synthase, and expansin, lncRNA-miRNA-mRNA regulatory networks related to coma cell wall synthesis and remodeling were developed. This study not only enhances the comprehension of lncRNA but also provides novel insights into the molecular mechanisms governing the initiation and development of poplar coma. [ABSTRACT FROM AUTHOR]

Early‐life stress (ES) induced by maternal separation (MS) remains a proven causality of anxiety and memory deficits at later stages of life. Emerging studies have shown that MS‐induced gene expression in the hippocampus is operated at the level of transcription. However, the extent of involvement of non‐coding RNAs in MS‐induced behavioural deficits remains unexplored. Here, we have investigated the role of synapse‐enriched long non‐coding RNAs (lncRNAs) in anxiety and memory upon MS. We observed that MS led to an enhancement of expression of the lncRNA growth arrest specific 5 (Gas5) in the hippocampus; accompanied by increased levels of anxiety and deficits in spatial memory. Gas5 knockdown in early life was able to reduce anxiety and partially rescue the spatial memory deficits of maternally separated adult mice. However, the reversal of MS‐induced anxiety and memory deficits is not attributed to Gas5 activity during neuronal development as Gas5 RNAi did not influence spine development. Gene Ontology analysis revealed that Gas5 exerts its function by regulating RNA metabolism and translation. Our study highlights the importance of MS‐regulated lncRNA in anxiety and spatial memory. [ABSTRACT FROM AUTHOR]

Adipocytes are crucial for maintaining energy balance. Adipocyte differentiation involves distinct stages, including the orientation stage, clone amplification stage, clone amplification termination stage, and terminal differentiation stage. Understanding the regulatory mechanisms governing adipogenic differentiation is essential for comprehending the physiological processes and identifying potential biomarkers and therapeutic targets for metabolic diseases, ultimately improving glucose and fat metabolism. Adipogenic differentiation is influenced not only by key factors such as hormones, the peroxisome proliferator-activated receptor (PPAR) family, and the CCATT enhancer-binding protein (C/EBP) family but also by noncoding RNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Among these, lncRNA has been identified as a significant regulator in adipogenic differentiation. Research has demonstrated various ways in which lncRNAs contribute to the molecular mechanisms of adipogenic differentiation. Throughout the adipogenesis process, lncRNAs modulate adipocyte differentiation and development by influencing relevant signaling pathways and transcription factors. This review provides a brief overview of the function and mechanism of lncRNAs in adipogenic differentiation. [ABSTRACT FROM AUTHOR]

Our understanding of RNA biology has evolved with recent advances in research from it being a non-functional product to molecules of the genome with specific regulatory functions. Competitive endogenous RNA (ceRNA), which has gained prominence over time as an essential part of post-transcriptional regulatory mechanism, is one such example. The ceRNA biology hypothesis states that coding RNA and non-coding RNA co-regulate each other using microRNA (miRNA) response elements. The ceRNA components include long non-coding RNAs, pseudogene and circular RNAs that exert their effect by interacting with miRNA and regulate the expression level of its target genes. Emerging evidence has revealed that the dysregulation of the ceRNA network is attributed to the pathogenesis of various cancers, including the head and neck squamous cell carcinoma (HNSCC). This is the most prevalent cancer developed from the mucosal epithelium in the lip, oral cavity, larynx and pharynx. Although many efforts have been made to comprehend the cause and subsequent treatment of HNSCC, the morbidity and mortality rate remains high. Hence, there is an urgent need to understand the holistic progression of HNSCC, mediated by ceRNA, that can have immense relevance in identifying novel biomarkers with a defined therapeutic intervention. In this review, we have made an effort to highlight the ceRNA biology hypothesis with a focus on its involvement in the progression of HNSCC. For the identification of such ceRNAs, we have additionally highlighted a number of databases and tools. [ABSTRACT FROM AUTHOR]

Apoptosis can be known as a key factor in the pathogenesis of neurodegenerative disorders. In disease conditions, the rate of apoptosis expands and tissue damage may become apparent. Recently, the scientific studies of the non-coding RNAs (ncRNAs) has provided new information of the molecular mechanisms that contribute to neurodegenerative disorders. Numerous reports have documented that ncRNAs have important contributions to several biological processes associated with the increase of neurodegenerative disorders. In addition, microRNAs (miRNAs), circular RNAs (circRNAs), as well as, long ncRNAs (lncRNAs) represent ncRNAs subtypes with the usual dysregulation in neurodegenerative disorders. Dysregulating ncRNAs has been associated with inhibiting or stimulating apoptosis in neurodegenerative disorders. Therefore, this review highlighted several ncRNAs linked to apoptosis in neurodegenerative disorders. CircRNAs, lncRNAs, and miRNAs were also illustrated completely regarding the respective signaling pathways of apoptosis. [ABSTRACT FROM AUTHOR]

Epithelial mesenchymal transition (EMT) occurring in retinal pigment epithelial cells (RPE) is a crucial mechanism that contributes to the development of age-related macular degeneration (AMD), a pivotal factor leading to permanent vision impairment. Long non-coding RNAs (lncRNAs) have emerged as critical regulators orchestrating EMT in RPE cells. In this study, we explored the function of the lncRNA CYTOR (cytoskeleton regulator RNA) in EMT of RPE cells and its underlying mechanisms. Through weighted correlation network analysis, we identified CYTOR as an EMT-related lncRNA associated with AMD. Experimental validation revealed that CYTOR orchestrates TGF-β1-induced EMT, as well as proliferation and migration of ARPE-19 cells. Further investigation demonstrated the involvement of CYTOR in regulating the WNT5A/NFAT1 pathway and NFAT1 intranuclear translocation in the ARPE-19 cell EMT model. Mechanistically, CHIP, EMSA and dual luciferase reporter assays confirmed NFAT1's direct binding to CYTOR's promoter, promoting transcription. Reciprocally, CYTOR overexpression promoted NFAT1 expression, while NFAT1 overexpression increased CYTOR transcription. These findings highlight a mutual promotion between CYTOR and NFAT1, forming a positive feedback loop that triggers the EMT phenotype in ARPE-19 cells. These discoveries provide valuable insights into the molecular mechanisms of EMT and its association with AMD, offering potential avenues for targeted therapies in EMT-related conditions, including AMD. [ABSTRACT FROM AUTHOR]

Abstract Background Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. Methods Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. Results The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM − receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. Conclusions Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC.

Alzheimer's disease (AD) is the most frequent type of dementia, presenting a substantial danger to the health and well-being of the aged population. It has arisen as a significant public health problem with considerable socioeconomic repercussions. Unfortunately, no effective treatments or diagnostic tools are available for Alzheimer's disease. Despite substantial studies on the pathophysiology of Alzheimer's, the molecular pathways underpinning its development remain poorly understood. Long non-coding RNAs (lncRNAs) vary in size from 200 nucleotides to over 100 kilobytes and have been found to play critical roles in various vital biological processes that play critical in developing Alzheimer's disease. This review intends to examine the functions of long non-coding RNAs in diagnosing and treating Alzheimer's disease and their participation in immunological responses associated with AD.

Abstract Background Plant long non-coding RNAs (lncRNAs) have important regulatory roles in responses to various biotic and abiotic stresses, including light quality. However, no lncRNAs have been specifically linked to the Shade Avoidance Response (SAS). Results To better understand the involvement of lncRNAs in shade avoidance, we examined RNA-seq libraries for lncRNAs with the potential to function in the neighbor proximity phenomenon in Arabidopsis thaliana (A. thaliana). Using transcriptomes generated from seedlings exposed to high and low red/far-red (R/FR) light conditions, we identified 13 lncRNA genes differentially expressed in cotyledons and 138 in hypocotyls. To infer possible functions for these lncRNAs, we used a ‘guilt-by-association’ approach to identify genes co-expressed with lncRNAs in a weighted gene co-expression network. Of 34 co-expression modules, 10 showed biological functions related to differential growth. We identified three potential lncRNAs co-regulated with genes related to SAS. T-DNA insertions in two of these lncRNAs were correlated with morphological differences in seedling responses to increased FR light, supporting our strategy for computational identification of lncRNAs involved in SAS. Conclusions Using a computational approach, we identified multiple lncRNAs in Arabidopsis involved in SAS. T-DNA insertions caused altered phenotypes under low R/FR light, suggesting functional roles in shade avoidance. Further experiments are needed to determine the specific mechanisms of these lncRNAs in SAS.

Abstract Long noncoding RNAs (lncRNAs) are versatile RNA molecules recently identified as key regulators of gene expression in response to environmental stress. Our primary focus in this study was to develop a robust computational pipeline for identifying structurally identical lncRNAs across replicates from publicly available bulk RNA-seq datasets. In order to demonstrate the effectiveness of the pipeline, we utilized the transcriptome of the thermophilic fungus Thermothelomyces thermophilus and assessed the expression pattern of lncRNAs in conjunction with Heat Shock Proteins (HSP), a well-known protein family critical for the cell’s response to high temperatures. Our findings demonstrate that the identification of structurally identical transcripts among replicates in this thermophilic fungus ensures the reliability and accuracy of RNA studies, contributing to the validity of biological interpretations. Furthermore, the majority of lncRNAs exhibited a distinct expression pattern compared to HSPs. Our study contributes to advancing the understanding of the biological mechanisms comprising lncRNAs in thermophilic fungi.

Abstract Background There is an association between obesity and psychological disorders such as depression, anxiety, and stress. Environmental factors and genetics play a crucial role in this regard. Several long non-coding RNAs (lncRNAs) are involved in the pathophysiology of the nervous system. Additionally, we intend to investigate how dietary glycemic index and load relate to psychological disorders in women with obesity and overweight by identifying the possible interaction with metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1). Methods 267 overweight or obese women between the ages of 18 and 48 were recruited for the current study. A reliable and validated food frequency questionnaire (FFQ) consisting of 147 items assessed food consumption, glycemic load (GL), and glycemic index (GI). Depression-Anxiety-Stress Scales (DASS-21) were used to assess mental well-being. A real-time polymerase chain reaction (PCR) was used to assess transcript levels for lncRNAs MALAT1 and TUG1. Results In obese and overweight women, a positive correlation was found between anxiety and MALAT1 mRNA levels (P = 0.007, CC = 0.178). Age, energy intake, physical activity, total fat, income, marriage, thyroid, and BMI were adjusted, and GI and TUG1 were positively correlated on DASS-21 (β = 0.006, CI = 0.001, 0.01, P = 0.031), depression (β = 0.002, CI = 0.001, 0.004, P = 0.019), Stress (β = 0.003, CI = 0.001, 0.005, P = 0.027). The interaction of GL and TUG1 on stress was also observed (β = 0.03, CI = 0.001, 0.07, P = 0.048). Conclusions The lncRNA TUG1 appears to be associated with depression and stress through interaction with GI and correlated with stress by interaction with GL. To establish this concept, further research is required.

Abstract Long non-coding RNAs (lncRNAs), once considered transcriptional noise, have emerged as critical regulators of gene expression and key players in cancer biology. Recent breakthroughs have revealed that certain lncRNAs can encode small open reading frame (sORF)-derived peptides, which are now understood to contribute to the pathogenesis of various cancers. This review synthesizes current knowledge on the detection, functional roles, and clinical implications of lncRNA-encoded peptides in cancer. We discuss technological advancements in the detection and validation of sORFs, including ribosome profiling and mass spectrometry, which have facilitated the discovery of these peptides. The functional roles of lncRNA-encoded peptides in cancer processes such as gene transcription, translation regulation, signal transduction, and metabolic reprogramming are explored in various types of cancer. The clinical potential of these peptides is highlighted, with a focus on their utility as diagnostic biomarkers, prognostic indicators, and therapeutic targets. The challenges and future directions in translating these findings into clinical practice are also discussed, including the need for large-scale validation, development of sensitive detection methods, and optimization of peptide stability and delivery.

Background: Circular RNAs (Circ RNA) are a large class of non-coding RNAs which particularlystable RNAs and mostly originate from gene exons in animals. circRNAs are extremely abundantin the mammalian brains. They play role in the biological function and development of neurons.Nrf2 (nuclear factor erythroid 2–related factor 2) is a transcription factor that regulates cellularantioxidants and improves hippocampal synaptic plasticity, learning and memory. The aim ofthis study is the evaluation of Nrf2’s circRNA expression in the hippocampus of rats duringoxidative stress and the prediction of their function by bioinformatic tools. Methods: After evaluation of Nrf2’s circRNA prediction from circAtlas by BLAST, 3 out of 4sequences with high homology were selected and circ-Nrf2s expression was evaluated by qPCR,the interaction with micro RNAs and proteins was evaluated by miRDB, TargetScan, catRAPIDand HDOCK web server. Except control group, two groups of rats were treated with H2O2 (1%and 5%) then rats were sacrificed and hippocampal tissue was separated. qPCR was performedfor Nrf2 pathway gene expression and Nrf2 circRNAs. Then Circ-Nrf2-miRNA and 2circ-Nrf2-protein interaction were evaluated. Results: The most important circRNA that origin from Nrf2 is circ-Nrf2-1. Circ-Nrf2-1downregulates in oxidative stress and upregulates in 5% of H2O2 compared to 1%. However,linear Nrf2 was upregulated in both 1% and 5% H2O2. Circ-Nrf2-1 can bind to several miRNAsincluding miR-144-3p, miR-148a-5p, miR-155-5p. It also interacts with Celf1 which plays a rolein oxidative stress. Conclusion: According to results, it is plausible to suggest that circNrf2 may play a regulatoryrole in modulating oxidative stress.

Abstract Background Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear. Results Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells. Conclusions Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.

Abstract Background The escalating prevalence of metabolic diseases has led to a rapid increase in non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (NASH-HCC). While oxaliplatin (OXA)-based hepatic arterial infusion chemotherapy (HAIC) has shown promise in advanced-stage HCC patients, its efficacy in NASH-HCC remains uncertain. This study aims to assess the effectiveness of OXA-based HAIC and elucidate the mechanisms underlying OXA resistance in NASH-HCC. Methods The key lncRNAs were screened through RNA-seq analysis of NASH/non-NASH and OXA-sensitive/OXA-resistant (OXA-S/R) HCC tissues. The biological functions of the lnc-OXAR (OXA resistance–related lncRNA in NASH-HCC) in NASH-HCC were verified through a series of in vitro and in vivo experiments. The molecular mechanism of lnc-OXAR was elucidated by fluorescence in situ hybridization, immunoprecipitation-mass spectrometry (FISH), Immunoprecipitation-Mass Spectrometry (IP-MS), RNA pulldown, RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and a dual-luciferase reporter assay. Results NASH-HCC exhibited reduced responsiveness to OXA-based HAIC compared to non-NASH HCC. We identified and validated a novel transcript namedlnc-OXAR, which played a crucial role in conferring OXA resistance to NASH-HCC. Inhibition of lnc-OXAR suppressed HCC cell growth and restored OXA sensitivity both in NASH-HCC mouse models and in vitro. Mechanistically, lnc-OXAR recruited Ku70 and cystatin A (CSTA), preventing Ku70 degradation and facilitating DNA double-strand break (DSB) repair, thereby promoting OXA resistance in NASH-HCC. Additionally, WTAP-mediated m6A modification enhanced the stability of lnc-OXAR in an IGF2BP2-dependent manner. Notably, silencing lnc-OXAR significantly enhanced the response to OXA in patient-derived xenograft (PDX) models derived from NASH-HCC. Conclusions The reduced responsiveness of NASH-HCC to OXA treatment can be attributed to the upregulation of lnc-OXAR. Our findings provide a rationale for stratifying HCC patients undergoing OXA-based HAIC based on etiology. Lnc-OXAR holds promise as a novel target for overcoming OXA resistance in NASH-HCC and improving prognosis.

The IgLON family of cell adhesion molecules consists of five members (LSAMP, OPCML, neurotrimin, NEGR1, and IgLON5) discovered as supporters of neuronal development, axon growth and guidance, and synapse formation and maintenance. Tumour suppression properties have recently been emerging based on antiproliferative effects through the modulation of oncogenic pathways. Available evidence endorses a role for non-coding RNAs or microRNAs as relevant controllers of IgLON molecule expression that can impact their critical physiological and pathological roles. Current findings support a function for long non-coding RNAs and microRNAs in the modulation of LSAMP expression in cell senescence, cancer biogenesis, addiction, and pulmonary hypertension. For OPCML, data point to a role for several microRNAs in the control of tumorigenesis. MicroRNAs were detected in neurotrimin-mediated functions in cancer biogenesis and in Schwann cell responses to peripheral nerve injury. For NEGR1, studies have mainly investigated microRNA involvement in neuronal responses to ischaemic injury, although data also exist about tumorigenesis and endothelial cell dysfunction. For IgLON5, information is only available about microRNA involved in myocardial infarction. In conclusion, despite much information being still missing and further research needed, the emerging picture favours a model in which non-coding RNAs exert a crucial role in modulating IgLON expression, ultimately affecting their important physiological functions.

Abstract Background Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML. Methods In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML. Results We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells. Conclusions Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.

Abstract Background Long non-coding RNAs (lncRNAs) are abundant and closely related to the occurrence and development of human diseases. LncRNAs are known to play a key role in many cardiovascular diseases. The purpose of this study was to investigate the effect of the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) on the degree of coronary artery lesions and prognosis in patients with coronary artery disease (CAD). Methods Patients who underwent coronary angiography (CAG) and dynamical-single photon emission computed tomography (D-SPECT) were selected as study subjects, and the results of CAG were reviewed, and the patients were grouped according to SYNTAX score. Evaluate the factors affecting SYNTAX scores. The follow-up analysis was conducted, and the endpoint events were major adverse cardiovascular events (MACEs). Kaplan–Meier method was used to estimate the survival rate, and multivariate Cox regression was used to analyze the relationship between RMRP and MACEs. Results The expression level of serum RMRP in patients with CAD was significantly higher than that in healthy people. Multivariate Logistic regression analysis showed that age, low-density lipoprotein cholesterol (LDL-C), RMRP and rest left ventricular ejection fraction (LVEF) were independent factors that affected SYNTAX scores. There were 19 cases of MACEs in the high RMRP group and 9 cases in the low RMRP group, and there was a significant difference in the MACE free survival curve between the two groups. Multivariate Cox regression analysis showed that age, SYNTAX score, rest LVEF and RMRP were risk factors for MACEs. Conclusions Serum RMRP is a key factor affecting the degree of coronary artery disease and prognosis in CAD patients.

Objective To investigate the expression of long non-coding RNA (lncRNA), surfactant associated 1 pseudogene (SFTA1P) in lung squamous carcinoma and its effect on the biological functions of SFTA1P in lung squamous carcinoma cell lines. Methods Based on the cancer genome atlas (TCGA) database, the differential expression of SFTA1P in tumor and normal tissues were compared in patients diagnosed with lung squamous cell carcinoma. Then, the expression of SFTA1P was detected in human normal lung epithelial cell line BEAS-2B and lung squamous cell lines SK-MES-1 and H520 with real-time quantitative polymerase chain reaction (RT-qPCR). SK-MES-1 and H520 cells with overexpression and/or knockdown of SFTA1P were constructed by transfecting the overexpression plasmids (pcDNA3.1-SFTA1P) and small interfering RNAs (si-SFTA1P-1 and si-SFTA1P-2). CCK-8 assay and Transwell assay were used to investigate the effect of SFTA1P on biological functions in lung squamous carcinoma cells. Differential gene expression analysis, correlation analysis and functional enrichment analysis were employed to explore the potential mechanism that SFTA1P may affect biological functions of lung squamous cells. Results Analysis of TCGA showed that the expression of SFTA1P was significantly lower in lung squamous cell carcinoma tissue than adjacent normal tissue (P

Abstract Background The coronavirus pandemic that started in 2019 has caused the highest mortality and morbidity rates worldwide. Data on the role of long non-coding RNAs (lncRNAs) in coronavirus disease 2019 (COVID-19) is scarce. We aimed to elucidate the relationship of three important lncRNAs in the inflammatory states, H19, taurine upregulated gene 1 (TUG1), and colorectal neoplasia differentially expressed (CRNDE) with key factors in inflammation and fibrosis induction including signal transducer and activator of transcription3 (STAT3), alpha smooth muscle actin (α-SMA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in COVID-19 patients with moderate to severe symptoms. Methods Peripheral blood mononuclear cells from 28 COVID-19 patients and 17 healthy controls were collected. The real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of RNAs and lncRNAs. Western blotting analysis was also performed to determine the expression levels of STAT3 and α-SMA proteins. Machine learning and receiver operating characteristic (ROC) curve analysis were carried out to evaluate the distinguishing ability of lncRNAs. Results The expression levels of H19, TUG1, and CRNDE were significantly overexpressed in COVID-19 patients compared to healthy controls. Moreover, STAT3 and α-SMA expression levels were remarkedly increased at both transcript and protein levels in patients with COVID-19 compared to healthy subjects and were correlated with Three lncRNAs. Likewise, IL-6 and TNF-α were considerably upregulated in COVID-19 patients. Machine learning and ROC curve analysis showed that CRNDE-H19 panel has the proper ability to distinguish COVID-19 patients from healthy individuals (area under the curve (AUC) = 0.86). Conclusion The overexpression of three lncRNAs in COVID-19 patients observed in this study may align with significant manifestations of COVID-19. Furthermore, their co-expression with STAT3 and α-SMA, two critical factors implicated in inflammation and fibrosis induction, underscores their potential involvement in exacerbating cardiovascular, pulmonary and common symptoms and complications associated with COVID-19. The combination of CRNDE and H19 lncRNAs seems to be an impressive host-based biomarker panel for screening and diagnosis of COVID-19 patients from healthy controls. Research into lncRNAs can provide a robust platform to find new viral infection-related mediators and propose novel therapeutic strategies for viral infections and immune disorders.