Neonatal hypoxic-ischemic encephalopathy (HIE) remains a critical challenge in perinatal medicine. This study aimed to elucidate the transcriptomic landscape, focusing on long non-coding RNAs (lncRNAs) expression patterns in the brain tissues of a neonatal rat model of HIE.

We employed a modified Rice-Vannucci model to induce HIE in postnatal day 4 (P4) rats. The experimental groups were subjected to either 5 or 7 min of hypoxia (0 % O2, 100 % N2), while control animals were exposed to normoxic conditions.

RNA sequencing revealed a complex transcriptomic landscape in HIE brains, with approximately 80 million differentially expressed lncRNAs compared to controls. ELISA results demonstrated a significant upregulation of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and a concomitant decrease in anti-inflammatory IL-10 levels in brain tissue of HIE rats. qRT-PCR analysis revealed aberrant expression of several miRNAs. Biochemical assays indicated a marked reduction in superoxide dismutase (SOD) activity and an increase in malondialdehyde (MDA) content in HIE brain tissues.

This study highlights the potential regulatory roles of lncRNAs in HIE brains. The intricate interplay between lncRNAs, miRNAs, and mRNAs and alterations in inflammatory and oxidative stress markers suggests a complex regulatory network governing HIE pathogenesis.

The aim of our report was to recognize bladder cancer (BC)-specific serum exosome-derived long non-coding RNAs (lncRNAs) profile for early diagnosis of BC.

Potential BC-specific exosomal lncRNA indicators were discerned by genome-wide microarray profiling analysis of serum exosomes from 10 healthy participants and 10 early stage BC patients (Ta and T1), followed by multi-stage validation through quantitative real-time PCR (qRT-PCR) in BC cells, culture solution as well as 200 serum specimens and 50 tissue specimens from non-muscle-invasive bladder cancer (NMIBC) patients. The diagnostic panel was established using logistic regression and evaluated by receiver-operating characteristic (ROC) curve.

In the training stage, a diagnostic panel was constructed based on three up-regulated exosomal lncRNAs (G023016, RP11-553N19.1, and LINC0087) in NMIBC patients compared with healthy controls, yielding an area under ROC curve (AUC) of 0.827. We verified tumor-derived origin of these three lncRNAs which existed steadily in serum because of being enclosed in exosomes. The three-lncRNA panel was demonstrated to perform well in terms of NMIBC diagnosis, revealing AUC values of 0.809 and 0.812, respectively, in the following expanded validation stage and double-blind stage which was demonstrated to be significantly superior to that of urine cytology in double-blind stage (AUC = 0.630) (P < 0.0001). Moreover, serum exosome-derived G023016 significantly associated with tumor grade and TNM stage (P = 0.006 and P < 0.001, respectively), and LINC0087 significantly associated with TNM stage (P = 0.023).

The three-exosomal lncRNA signature could function as qualified blood-based non-invasive indicator for early diagnosis of BC.

Numerous studies have demonstrated that extracellular vesicles (EVs) carry a variety of noncoding RNAs (ncRNAs), which can be taken up by neighboring cells or transported to distant sites via bodily fluids, thereby facilitating intercellular communication and regulating multiple cellular functions. Within the tumor microenvironment, EV-ncRNA, on the one hand, regulate the expression of PD-L1, thereby influencing tumor immune evasion, promoting tumor cell proliferation, and enhancing tumor growth, invasion, and metastasis in vivo. On the other hand, these specific EV-ncRNAs can also modulate the functions of immune cells (such as CD8 + T cells, macrophages, and NK cells) through various molecular mechanisms, inducing an immunosuppressive microenvironment and promoting resistance to anti-PD-1 therapy. Therefore, delving into the molecular mechanisms underlying EV-ncRNA regulation of immune checkpoints presents compelling therapeutic prospects for strategies that selectively target EV-ncRNAs. In this review, we elaborate on the cutting-edge research progress related to EV-ncRNAs in the context of cancer and dissect their pivotal roles in the PD-1/PD-L1 immune checkpoint pathway. We also highlight the promising clinical applications of EV-ncRNAs in anti-PD-1/PD-L1 immunotherapy, bridging basic research with practical clinical applications.

In recent years, patients with early endometrial cancer (EC) can achieve a good prognosis through surgery. However, advanced and recurrent cases have still posed significant therapeutic challenges. This study aimed to investigate the biological function of long non-coding RNAs (lncRNAs) in EC and elucidate its underlying molecular mechanism. Through quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis, functional assays in cell lines, and bioinformatics approaches, we identified lncRNA MTA1-DT as a novel oncogenic factor in EC progression. RNA-seq and RT-qPCR analysis demonstrated that MTA1-DT was significantly upregulated with a 5-fold increase in EC cell lines compared to normal controls. Functional studies revealed that MTA1-DT promoted cell proliferation and migration. Mechanistically, we demonstrated that MTA1-DT physically interacted with purine-rich element binding protein-alpha (PURα) and facilitated its nuclear translocation, thereby enhancing its transcription factor activity. This nuclear accumulation of PURα promoted the transcription of downstream G2/M related genes, particularly EGF, leading to accelerated tumor growth. Thus, these results indicate that MTA1-DT exerts its oncogenic effects in EC through regulation of the cell cycle. Our findings establish MTA1-DT as a promising therapeutic target for EC treatment and provide new insights into the molecular mechanisms underlying EC progression.

Genome sequencing has enabled us to find functional peptides encoded by short open read frames (sORFs) in long non-coding RNAs (lncRNAs). sORFs-encoded peptides (SEPs) regulate gene expression, signaling, and so on and have significant roles, unlike common peptides. Various computational methods have been proposed. However, there is a lack of contributive features and effective models. Therefore, a high-throughput computational method to predict SEPs is needed.

We propose a computational method, SORFPP, to predict SEPs by mining feature information from multiple perspectives in an experimentally validated dataset from TranLnc. SORFPP fully extracts SEP sequence information using the protein language model ESM-2 and curated traditional encoding, including QSOrder, k-mer, etc. SORFPP uses CatBoost to solve the sparsity problem of traditional encoding. SORFPP also analyzes ESM-2 pre-training characterization information with the Self-attention model. Finally, an ensemble learning framework combines the two models and their results are fed into Logistic Regression model for accurate and robust predictions. For comparison, SORFPP outperforms other state-of-the-art models in Matthew correlation coefficient by 12.2%-24.2% on three benchmark datasets.

Integrating the ensemble learning strategy with contributive traditional features and the protein language encoding methods shows better performance. Datasets and codes are accessible at https://doi.org/10.6084/m9.figshare.28079897 and http://111.229.198.94:5000/.

Ischemic heart disease remains a major global health challenge, with myocardial ischemia-reperfusion injury (MIRI) being one of its most common and severe pathophysiological complications. The pathogenesis of MIRI is multifaceted, involving oxidative stress, inflammatory responses, apoptotic pathways, and autophagic regulation. Notably, autophagy exerts a dual regulatory effect, where maintaining optimal autophagic flux is essential for cardiac homeostasis. Emerging evidence underscores the crucial role of non-coding RNAs (ncRNAs) in modulating these pathological processes. In particular, long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) have been identified as key regulators of autophagy-mediated MIRI progression through complex molecular networks. This review provides a systematic analysis of the molecular pathways through which ncRNAs influence MIRI pathogenesis, with a specific focus on their autophagy-regulatory mechanisms. These insights may enhance our understanding of MIRI pathobiology and facilitate the development of novel therapeutic strategies.

The therapeutic efficacy of osimertinib (OSI) in EGFR-mutant lung cancer is ultimately limited by the onset of acquired resistance, of which the mechanisms remain poorly understood. Here, we identify a novel long non-coding RNA, LRTOR, as a key driver of OSI resistance in non-small cell lung cancer (NSCLC). Clinical data indicate that elevated LRTOR expression correlates with poor prognosis in OSI-resistant patients. Functionally, LRTOR promotes tumor growth and confers OSI resistance both in vitro and in vivo. Mechanistically, LRTOR shields YAP from LATS-mediated phosphorylation at Ser127 and Ser381, preventing its proteasomal degradation. Furthermore, LRTOR facilitates the interaction between YAP and KCMF1, promoting K63-linked ubiquitination, nuclear translocation of YAP, and formation of the YAP/TEAD1 transcriptional complex, which in turn triggers the transcription of LRTOR, establishing a positive feedback loop that amplifies oncogenic signaling of YAP and consequently induces OSI resistance. LRTOR depletion by siRNA restores OSI sensitivity in resistant tumors, as demonstrated in patient-derived organoid xenograft models. Our findings unveil LRTOR as a central regulator of OSI resistance in NSCLC and propose it as a promising therapeutic and prognostic target for overcoming acquired OSI resistance in EGFR-mutant lung cancer.

Metastasis is a leading cause of colorectal cancer (CRC)-related mortality, yet its molecular mechanisms remain poorly understood. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of CRC metastasis, but their specific roles are not fully elucidated. This study identifies and characterizes a novel lncRNA LINC02167 as a critical regulator of CRC metastasis.

LINC02167 expression was analyzed in CRC tissues via real-time quantitative polymerase chain reaction and fluorescence in situ hybridization. Functional assays evaluated its role in CRC cell migration, invasion, and metastasis in vitro and in vivo. Mechanistic exploration involves a combination of techniques, including RNA sequencing, mass spectrometry, RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, luciferase reporter assays, RNA stability assays, and bioinformatics analysis, to uncover the molecular interactions and pathways regulated by LINC02167.

LINC02167 is markedly upregulated in CRC tissues and strongly correlates with advanced clinical features and poor prognosis. Functional analyses reveal that LINC02167 enhances CRC cell migration and invasion in vitro and promotes metastasis in vivo. Mechanistically, LINC02167 serves as a molecular scaffold, forming a complex with YBX1 and ILF3 to facilitate YBX1 binding to NSUN2-mediated m5C modification sites on KSR1 mRNA, thereby stabilizing KSR1 mRNA and activating the ERK/MAPK signaling pathway to drive CRC metastasis. Additionally, MYC-driven transcriptional activation leads to the upregulation of LINC02167 in CRC.

This study uncovers a novel mechanism through which LINC02167 promotes the ERK/MAPK pathway and CRC metastasis via m5C modification, underscoring its potential as a promising therapeutic target for metastatic CRC treatment.

In the United States, an estimated 38 million individuals (10% of the population) have type 2 diabetes mellitus (T2D), while approximately 97.6 million adults (38%) have prediabetes. Long noncoding RNAs (lncRNAs) are critical regulators of gene expression and metabolism. We were the first to demonstrate that lncRNA Growth Arrest-Specific Transcript 5 (GAS5 (human)/gas5 (mouse)) is decreased in the serum of T2D patients and established GAS5 as a biomarker for T2D diagnosis and onset prediction, now validated by other groups. We further demonstrated that GAS5 depletion impaired glucose uptake, decreased insulin receptor levels, and inhibited insulin signaling in human adipocytes, highlighting its potential as a therapeutic target in T2D. To address this, we developed NPC86, a small-molecule compound that stabilizes GAS5 by disrupting its interaction with UPF-1, an RNA helicase involved in nonsense-mediated decay (NMD) that regulates RNA stability. NPC86 increased GAS5 and insulin receptor (IR) levels, enhanced insulin signaling, and improved glucose uptake in vitro. In this study, we tested the efficacy of NPC86 in vivo in a diet-induced obese diabetic (DIOD) mouse model, and NPC86 treatment elevated gas5 levels, improved glucose tolerance, and enhanced insulin sensitivity, with no observed toxicity or weight changes. A transcriptomics analysis of adipose tissue revealed the upregulation of insulin signaling and metabolic pathways, including oxidative phosphorylation and glycolysis, while inflammatory pathways were downregulated. These findings highlight NPC86's therapeutic potential in T2D.

Endothelial cell (EC) dysfunction and vascular inflammation are critical in the initiation and progression of atherosclerosis. Long noncoding RNAs play a critical role in vascular pathology, but relatively little is known about their involvement in controlling vascular inflammation. MIR181A1HG is a conserved long noncoding RNA located in juxtaposition with miR-181a1 and miR-181b1, both involved in vascular inflammation. The study aims to investigate the role of MIR181A1HG in regulating vascular inflammation.

We examined the expression of MIR181A1HG in both human and mouse atherosclerotic lesions. Loss-of-function and gain-of-function studies, and multiple RNA-protein interaction assays were used to investigate the role and molecular mechanisms of MIR181A1HG in vascular inflammation and atherosclerosis. The atherosclerotic phenotypes of MIR181A1HG-/-ApoE-/- mice were analyzed in combination with single-cell RNA sequencing. The transcriptional regulation of MIR181A1HG was verified through luciferase reporter and chromatin immunoprecipitation assays.

MIR181A1HG expression was abundant in ECs and significantly increased in both human and mouse atherosclerotic lesions. MIR181A1HG-/-ApoE-/- mice had reduced NLRP (NLR family pyrin domain containing) 3 inflammasome signaling, EC activation, monocyte infiltration, and atherosclerotic lesion formation. Genetic deletion of MIR181A1HG in myeloid sells did not alter the progression of atherosclerosis. Single-cell RNA sequencing analysis revealed that MIR181A1HG deficiency reduced the proportion of immune cells and enriched anti-inflammation pathways in EC clusters in atherosclerotic lesions. In contrast, EC-specific MIR181A1HG overexpression promoted NLRP3 inflammasome signaling, EC activation, and atherosclerotic lesion formation, effects that were reversed by pharmacological inhibition of NLRP3 (MCC950). MIR181A1HG was transcriptionally activated via an NF-κB (nuclear factor kappa B)/p65-dependent pathway. Mechanistically, MIR181A1HG mediated these effects on regulating NLRP3 inflammasome and EC activation in part through decoying Foxp1 (forkhead box transcription factor 1) away from the promoters of target genes, which was independent of the miR-181a1/b1 cluster. Finally, EC-specific Foxp1 silencing reversed the antiatherosclerotic effect mediated by MIR181A1HG-deletion in vivo.

These findings identify MIR181A1HG as a central driver of vascular inflammation in atherosclerosis by its ability to decoy Foxp1 away from target gene promoters and activate NLRP3 inflammasome in the vascular endothelium. Our study suggests MIR181A1HG as a future therapeutic target for vascular inflammatory disease states.

Periodontal ligament stem cells (PDLSCs) are key cells that suppress periodontal damage during both the progression and recovery stages of periodontitis. Although substantial evidence has demonstrated that incubation under an inflammatory condition may accelerate senescence of PDLSCs, whether cellular senescence in response to inflammatory incubation contributes to cell dysfunction remain unexplored. In this study, we first observed inflammation-caused PDLSC senescence in periodontitis based on comparisons of matched patients, and this cellular senescence was demonstrated in healthy cells that were subjected to inflammatory conditions. We subsequently designed further experiments to investigate the possible mechanism underlying inflammation-induced PDLSC senescence with a particular focus on the role of long noncoding RNAs (lncRNAs). LncRNA microarray analysis and functional gain/loss studies revealed SLC30A4-AS1 as a regulator of inflammation-mediated PDLSC senescence. By full-length transcriptome sequencing, we found that SLC30A4-AS1 interacted with SRSF3 to affect the alternative splicing (AS) of TP53BP1 and alter the expression of TP53BP1-204. Further functional studies showed that decreased expression of TP53BP1-204 reversed PDLSC senescence, and SLC30A4-AS1 overexpression-induced PDLSC senescence was abolished by TP53BP1-204 knockdown. Our data suggest for the first time that SLC30A4-AS1 plays a key role in regulating PDLSC senescence in inflammatory environments by modulating the AS of TP53BP1.

Porphyromonas gingivalis (P. gingivalis) is one of the major pathogens causing periodontitis and apical periodontitis (AP). Long noncoding RNA (lncRNA) can regulate cellular mineralization and inflammatory diseases. The aim of this study was to investigate the role and mechanism of lncRNA in P. gingivalis-stimulated cementoblast mineralization. In vivo, C57BL/6 mice were divided into the healthy, the AP, and AP + P. gingivalis groups (n = six mice per group). Micro computed tomography, immunohistochemistry staining, and fluorescence in situ hybridization were used to observe periapical tissue. In vitro, cementoblasts were treated with osteogenic medium or P. gingivalis. Pluripotency associated transcript 3 (Platr3), interleukin 1 beta (IL1B), and osteogenic markers were analyzed by quantitative real-time polymerase chain reaction and western blot. RNA pull-down and RNA immunoprecipitation assays were used to detect proteins that bind to Platr3. RNA sequencing was performed in Platr3-silenced cementoblasts. In vivo, P. gingivalis promoted periapical tissue destruction and IL1B expression, but inhibited Platr3 expression. In vitro, P. gingivalis facilitated IL1B expression (P < 0.001), whereas suppressed the expression of Platr3 (P < 0.001) and osteogenic markers (P < 0.01 or 0.001). In contrast, Platr3 overexpression alleviated the repressive effect of P. gingivalis on cementoblast mineralization (P < 0.01 or 0.001). Furthermore, Platr3 bound to nudix hydrolase 21 (NUDT21) and regulated the nuclear factor-κB (NF-κB) signaling pathway. Knocking down NUDT21 suppressed osteogenic marker expression and activated the above signaling pathway. Collectively, the results elucidated that Platr3 mediated P. gingivalis-suppressed cementoblast mineralization through the NF-κB signaling pathway by binding to NUDT21.

Breast cancer (BC) is a malignant tumor that has the highest morbidity and mortality rates in the female population, and its high tendency to metastasize is the main cause of poor clinical prognosis. Long non-coding RNAs (lncRNAs) have been extensively documented to exhibit aberrant expression in various cancers and influence tumor progression via multiple molecular pathways. These lncRNAs not only modulate numerous aspects of gene expression in cancer cells, such as transcription, translation, and post-translational modifications, but also play a crucial role in the reprogramming of energy metabolism by regulating metabolic regulators, which is particularly significant in advanced BC. This review examines the characteristics and mechanisms of lncRNAs in regulating BC cells, both intracellularly (e.g., cell cycle, autophagy) and extracellularly (e.g., tumor microenvironment). Furthermore, we explore the potential of specific lncRNAs and their regulatory factors as molecular markers and therapeutic targets. Lastly, we summarize the application of lncRNAs in the treatment of advanced BC, aiming to offer novel personalized therapeutic options for patients.

Stanford-A Aortic dissection (TAAD) is a rare and fatal disease, genetic factors remains poorly known. Study has confirmed that lncRNA play an important role in various physiological and pathological processes. This study attempts to elucidate the underlying molecular mechanisms of TAAD through lncRNA-associated competitive endogenous RNA (ceRNA) networks.

In this study, aortic vascular of 5 TAAD and 5 control (ischemic heart disease) were subjected to lncRNA and mRNA microarray analysis, and differentially expressed mRNAs (DEGs) and differentially expressed lncRNAs (DELs) were identified. The differentially expressed miRNAs (DEmiR) were screened by GSE98770 dataset. The ceRNA network (lncRNA-miRNA-mRNA) was constructed by bioinformatics analysis. The accuracy of hub genes as biomarkers for predicting TAAD was evaluated by receiver operating characteristic (ROC) curve. Finally, the biomarkers were verified by assessing their mRNA levels using real-time quantitative PCR (RT-qPCR).

This study revealed 161 DELs, 87 DEmiRs and 103 DEGs between TAAD and control. We constructed ceRNA networks based on the screened 1 lncRNA, 4 miRNAs and 7 mRNAs. We identified three lncRNA-miRNA-mRNA regulatory axes, namely the VCAN axis (LINC01355 - hsa-miR-186-5p / hsa-miR-30a-5p /hsa-miR-30c-5p - VCAN), LOX axis (LINC01355-hsa-miR-145-5p/hsa-miR-186-5p/ hsa-miR-30a-5p / hsa-miR-30c-5p - LOX), and CTSS axis (LINC01355 - hsa-miR-186-5p - CTSS) based on gene ontology, pathway enrichment and protein-protein interaction (PPI) network, which may play an important role in TAAD. The clinical performance of VCAN, CTSS, and LOX in TAAD diagnosis was evaluated, and the AUCs of VCAN, CTSS, and LOX were 0.920 (p<0.001), 0.880 (p=0.002) and 0.840 (p=0.011), respectively. Furthermore, mRNA expression of VCAN in human aortic tissue significantly overexpressed in the TAAD patients (p<0.001).

This study identifies three ceRNA interaction axes, especially VCAN associated with TAAD pathogenesis, providing fundamentals of bioinformatics for understanding the molecular mechanisms of TAAD pathogenesis and developing potential therapeutic strategies for TAAD.

The CDKN2A gene, responsible for encoding the tumor suppressors p16(INK4A) and p14(ARF), is frequently inactivated in non-small cell lung cancer (NSCLC). Herein, an uncharacterized long non-coding RNA (lncRNA) (ENSG00000267053) on chromosome 19p13.12 was found to be overexpressed in NSCLC cells with an active, wild-type CDKN2A gene. This lncRNA, named cyclin-dependent kinase inhibitor 2A-regulated lncRNA (CyKILR), also correlated with an active WT STK11 gene, which encodes the tumor suppressor, liver kinase B1. CyKILR displayed two splice variants, CyKILRa (exon 3 included) and CyKILRb (exon 3 excluded), which are cooperatively regulated by CDKN2A and STK11 as knockdown of both tumor suppressor genes was required to induce a significant loss of exon 3 inclusion in mature CyKILR RNA. CyKILRa localized to the nucleus, and its downregulation using antisense RNA oligonucleotides enhanced cellular proliferation, migration, clonogenic survival, and tumor incidence. In contrast, CyKILRb localized to the cytoplasm, and its downregulation using small interfering RNA reduced cell proliferation, migration, clonogenic survival, and tumor incidence. Transcriptomics analyses revealed the enhancement of apoptotic pathways with concomitant suppression of key cell-cycle pathways by CyKILRa demonstrating its tumor-suppressive role. CyKILRb inhibited tumor suppressor miRNAs indicating an oncogenic nature. These findings elucidate the intricate roles of lncRNAs in cell signaling and tumorigenesis.

Long noncoding RNAs (lncRNAs) play numerous roles in cellular biology and alterations in lncRNA expression profiles have been implicated in a variety of cancers. Here, we identify and characterize a lncRNA, TRIM28 Interacting DNA damage repair Enhancing Noncoding Transcript (TRIDENT), whose expression is induced upon epithelial growth factor receptor (EGFR) activation, and which exerts pro-oncogenic functions in EGFR-driven non-small cell lung cancer. Knocking down TRIDENT leads to decreased tumor-cell proliferation in both in vitro and in vivo model systems and induces sensitization to chemotherapeutic drugs. Using ChIRP-MS analysis we identified TRIM28 as a protein interactor of TRIDENT. TRIDENT promotes phosphorylation of TRIM28 and knocking down TRIDENT leads to accumulation of DNA damage in cancer cells via decreased TRIM28 phosphorylation. Altogether, our results reveal a molecular pathway in which TRIDENT regulates TRIM28 phosphorylation to promote tumor cell growth and drug resistance. Our findings suggest that TRIDENT can be developed as a biomarker or therapeutic target for EGFR mutant non-small cell lung cancer.

More research has been done on the correlation between exercise and cancer, which has revealed several ways that physical activity decreases the risk of developing the disease. The developing function of lncRNAs as an important molecular link between exercise and cancer suppression is the main topic of this review. According to recent research, regular physical exercise also alters the expression levels of several lncRNAs, which are generally elevated in cancer. A complex network of interactions that may provide protective effects against carcinogenesis is suggested by the contribution of these lncRNAs in various cellular processes, such as epigenetic alterations, proliferation, and apoptosis regulation. We offer a comprehensive summary of the existing information regarding specific lncRNAs that are influenced by physical activity and could potentially impact cancer-related processes. We also go over the difficulties in interpreting these alterations, taking into account the fact that several lncRNAs have a dual function in promoting and preventing cancer in various physiological settings. To understand the complex impacts of exercise-induced lncRNA regulation in cancer biology, more study is required. The critique strongly highlights the possibility of lncRNAs serving as both indicators and treatment prospects for cancer-preventive strategies.

Thyroid eye disease (TED) is a visually debilitating and cosmetically disfiguring orbital disorder, characterized by the remodeling of extraocular muscles (EOMs). This study aimed to investigate the role of long non-coding RNA (lncRNA) ENST00000581911 in the EOMs of TED.

LncRNA microarray analysis was performed on EOM tissues sampled from patients with TED and patients with concomitant esotropia. LncRNA ENST00000581911 was identified and subjected to bioinformatics analysis. High-throughput RNA sequencing, CCK-8 assay, CFSE staining, and ELISA were used to investigate the regulatory function of ENST00000581911 in vitro. Furthermore, RNA pull-down, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and western blot (WB) analyses were applied to identify the RNA-binding protein (RBP) interacting with ENST00000581911.

A total of 1261 lncRNAs were found to be differentially expressed in the EOMs of TED, with 648 upregulated and 613 downregulated lncRNAs. Among these, the upregulated lncRNA ENST00000581911 exhibited the highest expression level, as validated by quantitative real-time PCR (qRT-PCR). Functional analysis demonstrated that ENST00000581911 might be involved in inflammatory response, regulation of muscle contraction, and amino sugar and nucleotide sugar metabolism. RNA sequencing of ENST00000581911-overexpressing and control orbital fibroblasts (OFs) showed that ENST00000581911 might play a regulatory role in DNA replication, extracellular matrix, and cell cycle. Furthermore, KHSRP was identified as the RBP of ENST00000581911. Overexpression of ENST00000581911 promoted cell proliferation and hyaluronic acid secretion in OFs, whereas silencing KHSRP attenuated these effects.

This study provides novel insights into the role of lncRNA ENST00000581911 in the pathogenesis of EOM remodeling in TED. ENST00000581911 may serve as a potential therapeutic target of TED.

PurposeWe aimed to exploit a urine exosomal long non-coding RNAs (lncRNAs) fingerprint to facilitate the early diagnosis of bladder cancer.MethodsMicroarray differential expression profiling of lncRNAs was for the first time employed in urine exosomes from 10 non-muscle-invasive bladder cancer (NMIBC) patients and 10 healthy controls to screen out candidate exosomal lncRNA biomarkers, which were then verified by quantitative real-time polymerase chain reaction in three independent phases including bladder cancer cells, culture fluid and 200 NMIBC participants. Logistic regression was performed to construct a diagnostic model-the diagnostic potency of which was assessed.ResultsThe profile of three exosome-derived lncRNAs (CCDC148-AS1, XLOC_006419, and RP5-1148A21.3) was screened and further verified to be notably over-expressed in NMIBC patients and bladder cancer cell lines, and exhibited area under the receiver-operating characteristic curve values of 0.873, 0.825, and 0.834, respectively, in training, validation, and double-blind validation phases. The profile was superior to urinary cytology in discriminating NMIBC from healthy controls (P < 0.0001). A significant correlation existed between a higher level of CCDC148-AS1 and a higher tumor grade (P < 0.001), and up-regulated CCDC148-AS1 as well as XLOC_006419 were statistically related with tumor node metastasis stage (P = 0.004 and P = 0.031, respectively). These three identified lncRNAs were confirmed to originate from bladder cancer cells and be packaged within exosomes, thus staying sufficiently stable in urine.ConclusionsTumor-originated urine exosomal lncRNAs, as fingerprint in NMIBC, exhibited satisfying clinical significance in early diagnosis of bladder cancer.

Metabolic-dysfunction-associated steatotic liver disease is one of the most common chronic liver diseases worldwide and has no approved treatment thus far. Here we report that the hepatic overexpression of Gm35585, a novel lncRNA downregulated in the livers of mice fed a high-fat diet, is functionally important in alleviating hepatic lipid accumulation pathologies. Gm35585 activates the peroxisome proliferator-activated receptor α (PPARα) signaling pathway and promotes the expression of downstream PPARα-target gene, enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), which is one of the four enzymes of the peroxisomal β-oxidation pathway. Activation of EHHADH promotes the oxidation of long-chain fatty acids (LCFAs), and the increased levels of hepatic LCFAs contribute to metabolic-dysfunction-associated steatotic liver disease. Mechanistically, Gm35585 binds to retinoid X receptor α (RXRα) and then forms a PPARα/RXRα heterodimer with PPARα and guides the heterodimer to recognize the promoter of EHHADH, which is called peroxisome proliferator-activated receptor response element, causing transcriptional activation of EHHADH. Taken together, Gm35585 is a hepatic lipid metabolism regulator that activates EHHADH transcription, promoting peroxisomal β-oxidation of LCFAs and ultimately ameliorating diet-induced fatty liver.

MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs found in eukaryotes with post-transcriptional regulatory functions. A variety of miRNAs is differentially expressed in cancer tissues and thus can be used as biomarkers. microRNA-135b-5p (miR-135b) has been shown to be involved in the pathological processes of a variety of neoplastic and non-neoplastic diseases. Under different conditions, miR-135b has different tumor suppressive and carcinogenic effects. miR-135b regulates the development of cancer, including metabolism, proliferation, apoptosis, invasion, fibrosis, angiogenesis, immunomodulation, and drug resistance. miR-135b can be used as a new biomarker for tumor diagnosis and prognosis, which has the potential for clinical guidance. This article reviews the relevant research on miR-135B in the field of tumors, including the biogenesis background of miR-135b, the expression of miR-135b in tumors, and the related targets and signaling pathways of miR-135b mediating tumor progression in order to sort out and explore the clinical transformation value of miR-135b.

Targeted protein degradation has become a notable drug development strategy, but its application has been limited by the dependence on protein-based chimeras with restricted genetic manipulation capabilities. The use of long non-coding RNAs (lncRNAs) has emerged as a viable alternative, offering interactions with cellular proteins to modulate pathways and enhance degradation capabilities. Here we introduce a strategy employing artificial lncRNAs (alncRNAs) for precise targeted protein degradation. By integrating RNA aptamers and sequences from the lncRNA HOTAIR, our alncRNAs specifically target and facilitate the ubiquitination and degradation of oncogenic transcription factors and tumor-related proteins, such as c-MYC, NF-κB, ETS-1, KRAS and EGFR. These alncRNAs show potential in reducing malignant phenotypes in cells, both in vitro and in vivo, offering advantages in efficiency, adaptability and versatility. This research enhances knowledge of lncRNA-driven protein degradation and presents an effective method for targeted therapies.

The aim of this study is to identify the lncRNA that directly interacts with NLRP3 molecules in RAW264.7 cells infected with S. typhimurium and its role in S. typhimurium-mediated pyroptosis. We have identified LncRNA-Gm17586, which directly interacts with NLRP3 in RAW264.7 cells infected with S. typhimurium. LncRNA-Gm17586 inhibits S. typhimurium-mediated pyroptosis in RAW264.7 cells. Overexpression of LncRNA-Gm17586 not only directly suppresses NLRP3 inflammasome activation but also enhances the binding affinity between Tnip1 and NLRP3, thereby indirectly facilitating Tnip1-mediated inhibition of the NLRP3 inflammasome. Consequently, this dual mechanism effectively inhibits S. typhimurium-induced pyroptosis. Our results demonstrate that LncRNA-Gm17586 directly interacts with NLRP3 during S. typhimurium-mediated pyroptosis and inhibits this process by enhancing the interaction between Tnip1 and NLRP3.

Traditional Chinese medicine (TCM) is widely used in China for disease treatment and has become a valuable resource for drug development due to its high efficacy and low risk of side-effects. However, growing toxicity reports has garnered significant global attention. A major challenge in addressing TCM-induced toxicity is lack of specific and sensitive biomarkers for diagnosing and predicting its toxicity. Identifying toxicological biomarkers reflecting TCM-induced toxicity is crucial for timely detection and intervention, and provides significant clues for elucidating the underlying toxic mechanism and key target.

This article aims to summarize and classify some potential toxicological biomarkers for side-effects induced by TCM and its contained phytochemical ingredients.

The keywords "biomarkers", "traditional Chinese medicine", "Chinese herb", "phytochemical ingredient", "natural product", "toxicity", "hepatotoxicity", "nephrotoxicity", "cardiotoxicity" were used to collect relevant information from literature databases (including PubMed, Web of Science) up to October 2024.

Research has indicated that more sensitive and specific biomarkers are needed for reflecting TCM's side-effects. PA-protein adducts and AA-DNA adducts could be served as diagnostic biomarkers for hepatotoxicity and nephrotoxicity induced by TCM containing PA and AA, respectively. Multiple miRNAs like miRNA-122-3p, miRNA-5099, and miRNA-21-3p, as well as some endogenous metabolites such as hypoxanthine, choline, and L-valine could be potential biomarkers associated with TCM-induced hepatotoxicity, nephrotoxicity, and cardiotoxicity.

In this review, different research demonstrates that DNA/protein-adducts, noncoding RNAs, endogenous metabolites and so on show the potential to be new early-warning biomarkers for TCM-induced toxicity with high specificity and sensitivity.

Eukaryotic genomes are extensively transcribed into various types of RNAs, many of which are physically associated with chromatin in cis at their transcription sites or in trans to other genomic loci. Emerging roles have been uncovered for these chromatin-associated RNAs (caRNAs) in gene regulation and genome organization, yet they remain challenging to interrogate. Here, we present TaDRIM-seq, a technique employing Protein G (PG)-Tn5-targeted DNA elements and in situ proximity ligation to concurrently probe caRNAs across diverse genomic regions as well as global RNA-RNA interactions within intact nuclei. Notably, this approach diminishes required cell inputs, minimizes hands-on time compared to established methodologies, and is compatible in both mammalian cells and plants. Using this technique, we identify extensive caRNAs at DNA anchor regions associated with chromatin loops and reveal diurnal variation in RNA-DNA and RNA-RNA connectivity networks within rice.

Primary open-angle glaucoma (POAG) is a subtype of glaucoma that accounts for 60%~70% of all cases. Its pathogenic mechanism is intricate and its pathogenic process is concealed. Numerous significant biological processes associated with POAG continue to be elucidated.

In this study, by exploring the expression data of POAG tissues and normal tissues, we mined the regulatory lncRNAs and mRNAs closely associated with the pathogenesis and progression of POAG by exploring a regulatory network of competing endogenous RNA (ceRNA), established by integrating gene expression data with the known lncRNA-miRNA and miRNA-mRNA-regulatory interactions. The key regulatory pathways and regulatory elements of POAG were identified by topological analysis. Simultaneously, the exome data of 28 cases with POAG and healthy controls were analyzed to identify high-frequency mutations and genes.

A total of 2712 differentially expressed genes were identified, including 1828 mRNAs and 884 lncRNAs. Network analysis suggested that lncRNAs such as HAGLR, HOTAIR and MIR29B2CHG, and mRNAs such as PPP6R3, BMPR2 and CFL2, may be involved in the onset and progression of POAG. In addition, 55 mutations with potential pathogenicity were identified.

These genes and mutations provide novel potential genetic heterogeneity and genetic susceptibility of POAG, as well as fresh suggestions for elucidating the molecular mechanism underlying the pathogenesis of POAG.

This article reviews the recent advances in pathogenesis, diagnosis and treatment of pancreatic cancer, as well as the relationship between long non-coding RNA (lncRNA) in disease progression. Unfortunately, pancreatic cancer has no early symptoms and quickly invades surrounding tissue and organs, making it one of the deadliest. Accordingly, we urgently need to identify high-risk individuals with precancerous lesions through screening methods to identify early disease, provide better prevention strategies and improve overall survival. LncRNAs have a variety of biological functions in both physiologic and pathophysiologic states including tumor growth, differentiation and proliferation. Herein we review the biological functions, expression patterns, clinical significance and targeted therapy potential of lncRNAs to provide new approaches for diagnosis and treatment in pancreatic cancer.

Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of homeobox (HOX) genes, underlying mechanisms remain elusive. Here, we report that the Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated mixed-lineage leukemia 1 (MLL1) recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes. HoxBlinc depletion in NUP98 fusion-driven leukemia impaired HoxBlinc binding, TAD integrity, MLL1 recruitment, and the MLL1-driven chromatin signature within HoxBlinc-defined TADs in a CCCTC-binding factor-independent (CTCF-independent) manner, leading to inhibited homeotic/leukemic oncogenes that mitigated NUP98 fusion-driven leukemogenesis in xenografted mouse models. Mechanistically, HoxBlinc overexpression in the mouse hematopoietic compartment induced leukemias resembling those in NUP98-PHF23-knockin (KI) mice via enhancement of HoxBlinc chromatin binding, TAD formation, and Hox gene aberration, leading to expansion of hematopoietic stem and progenitor cell and myeloid/lymphoid cell subpopulations. Thus, our studies reveal a CTCF-independent role of HoxBlinc in leukemic TAD organization and oncogene-regulatory networks.

Infertility is a widespread clinical problem that affects human reproduction and species persistence worldwide. Around 40-70% of cases are due to male reproductive defects. Functional spermatogenesis (sperm production through several coordinated events) is at the heart of male fertility. Non-coding RNAs (ncRNAs) are the primary regulators of gene expression, controlling extensive critical cellular processes, for example proliferation, differentiation, apoptosis, and reproduction. Due to advancements in high-throughput sequencing tools, many studies have revealed that ncRNAs are widely expressed in germ cells, meiosis, spermatogenesis, sperm fertility, early post-fertilization development, and male infertility. The present review examines the biology and function of ncRNAs, including microRNAs, circular RNAs, and long ncRNAs, in spermatogenesis, their correlation with infertility, and their potential as biomarkers for sperm quality and fertility. The function of ncRNA in Sertoli cells (SCs) and Leydig cells (LCs) is also outlined throughout this study, because spermatogenesis requires testicular somatic cells to be involved in testicular development and male fertility. Meanwhile, the future development of ncRNAs for the clinical treatment of male infertility is also anticipated and discussed.

Functional RNA participates in various life processes in cells. However, there is currently a lack of effective methods to screen for functional RNA. Here, we developed a technology named random high-throughput screening (rHTS). rHTS uses a random library of ∼250-nt synthesized RNA fragments, with high uniformity and abundance. These fragments are circularized into circular RNA by an auto-cyclizing ribozyme to improve their stability. Using rHTS, we successfully screened and identified three RNA fragments contributing significantly to the growth of Escherichia coli, one of which possesses coding potential. Moreover, we found that two noncoding RNAs (ncRNAs) effectively inhibited the growth of E. coli, in vivo rather than in vitro. Subsequently, we applied the rHTS to a coenzyme-dependent screening platform. In this context, two ncRNAs were identified that could effectively promote the conversion from NADPH to NADP+. Exogenous expression of these two ncRNAs was able to increase the conversion rate of glycerol dehydrogenase from glycerol to 1,3-dihydroxyacetone from 18.3% to 21.8% and 23.2%, respectively. These results suggest that rHTS is a powerful technology for functional RNA mining.

Histone demethylation in cardiac hypertrophy is poorly understood. This study aims to determine the role of the histone demethylase LSD1 in pathological cardiac hypertrophy. Both isoprenaline (ISO)-treated and transverse aortic constriction (TAC)-treated rats developed hypertrophic hearts. LSD1 was significantly decreased; the histone marks mono- and dimethyl H3K4 and H3K9 (H3K4me1/2 and H3K9me1/2) were significantly up-regulated in the hypertrophic heart tissue, as well as the expression of the ANP, α-HMC and MLV-2v genes. An LSD1 inhibitor, OG-L002 could also induce cardiac hypertrophy and enhance the induction of cardiac hypertrophy by ISO. Overexpressed LSD1 abolished ISO-induced cardiac hypertrophy and downregulated H3K4me1/2 and H3K9me1/2 expression. Overexpression of LSD1 also reduced the expression of ANP, α-HMC and MLV-2v. In addition, we have reported isoprenaline (ISO) as one of the histone demethylase LSD1 inhibitors. This was confirmed by molecular docking, molecular dynamic studies and a histone demethylation assay. The H3K4me1/2 expression increases with the incubation of ISO in HEK 293T and HELA cells. CaMKII could be significantly activated by the LSD1 inhibitor OG-L002 as well as by ISO in rats. In summary, we have identified a novel role for LSD1 in initiating and maintaining cardiac hypertrophy.

The IncRNA Malat1 was initially believed to be dispensable for physiology due to the lack of observable phenotypes in Malat1 knockout (KO) mice. However, our study challenges this conclusion. We found that both Malat1 KO and conditional KO mice in the osteoblast lineage exhibit significant osteoporosis. Mechanistically, Malat1 acts as an intrinsic regulator in osteoblasts to promote osteogenesis. Interestingly, Malat1 does not directly affect osteoclastogenesis but inhibits osteoclastogenesis in a non-autonomous manner in vivo via integrating crosstalk between multiple cell types, including osteoblasts, osteoclasts, and chondrocytes. Our findings substantiate the existence of a novel remodeling network in which Malat1 serves as a central regulator by binding to β-catenin and functioning through the β-catenin-OPG/Jagged1 pathway in osteoblasts and chondrocytes. In pathological conditions, Malat1 significantly promotes bone regeneration in fracture healing. Bone homeostasis and regeneration are crucial to well-being. Our discoveries establish a previous unrecognized paradigm model of Malat1 function in the skeletal system, providing novel mechanistic insights into how a lncRNA integrates cellular crosstalk and molecular networks to fine tune tissue homeostasis, remodeling and repair.

Pulmonary hypertension is a devastating vascular disorder characterized by extensive pulmonary vascular remodeling, ultimately leading to right ventricular failure and death. Activation of PDGF (platelet-derived growth factor) signaling promotes the hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs), thus contributing to the pulmonary vascular remodeling. However, the molecular mechanisms that govern hyperproliferation of PASMCs induced by PDGF remain largely unknown, including the contribution of long noncoding RNAs (lncRNAs). In this study, we aimed to identify a novel lncRNA regulated by PDGF implicated in PASMC proliferation in pulmonary vascular remodeling.

RNA-sequencing analysis was conducted to identify a novel lncRNA named vessel-enriched lncRNA regulated by PDGF-BB (platelet-derived growth factor-BB; VELRP). Functional investigations of VELRP were performed using knockdown and overexpression strategies along with RNA sequencing. Validation of the function and potential mechanisms of VELRP was performed through Western blot, RNA immunoprecipitation, and chromatin immunoprecipitation assays.

We identified a novel vessel-enriched lncRNA with an increased response to PDGF-BB stimulus. VELRP was identified as an evolutionarily conserved RNA molecule. Modulation of VELRP in PASMCs significantly altered cell proliferation. Mechanistically, VELRP enhances trimethylation of H3K4 (histone H3 lysine 4) by interacting with WDR5 (WD repeat-containing protein 5), leading to increased expression of CDK (cyclin-dependent kinase) 1, CDK2, and CDK4 and consequent hyperproliferation of PASMCs. The pathological relevance of VELRP upregulation in pulmonary artery was confirmed using rat pulmonary hypertension models in vivo, as well as in PASMCs from patients with idiopathic pulmonary arterial hypertension. Specific knockdown of VELRP in smooth muscle cells using adeno-associated virus type 9 SM22α (smooth muscle protein 22α) promoter-shRNA-mediated silencing of VELRP resulted in a significant decrease in right ventricular systolic pressure and vascular remodeling in rat pulmonary hypertension model.

VELRP, as an lncRNA upregulated by PDGF-BB, mediates PASMC proliferation via WDR5/CDK signaling. In vivo studies demonstrate that targeted intervention of VELRP in smooth muscle cells can prevent the development of pulmonary hypertension.

Lung adenocarcinoma is the most common type of lung cancer, accounting for approximately 40% of all lung cancer cases, and has the highest incidence among lung cancer subtypes. Recent studies have suggested that long non-coding RNAs (lncRNAs) play a crucial role in the initiation and progression of lung adenocarcinoma.

Based on integrative analysis through databases, we screened Long intergenic non-protein coding RNA 00839 (LINC00839) as one of the most highly upregulated lncRNAs in lung adenocarcinoma. In vitro and in vivo experiments demonstrated that LINC00839 promotes lung adenocarcinoma proliferation, migration, and invasion and that it is present in exosomes secreted by lung adenocarcinoma cells.

In the cytoplasm, LINC00839 regulates the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway by acting as a molecular sponge of miR-17-5p, thereby influencing the biological behavior of lung adenocarcinoma cells. LINC00839 binds to Polypyrimidine tract binding protein 1 (PTBP1) in the nucleus to regulate the nuclear translocation of NF-κB p65 molecules and, consequently, the transcription of downstream molecules.

Our study confirmed that LINC00839 promotes the biological progression of lung adenocarcinoma by performing dual roles in the cytoplasm and nucleus to co-regulate the NF-κB signaling pathway.