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.

Biomineralization to fabricate diverse morphology shell is typical character of bivalve species and ectopic calcification to form is the production of defense. Long non-coding RNAs (LncRNAs) plays critical roles in multiple cellular biological processes in invertebrate and vertebrate. However, LncRNAs remain poorly understood about expression and regulation roles in bivalve biomineralization studies. In this research, we systematically identified lncRNAs that functioned in differentiated mantle regions for fabricating two phenotypes of CaCO3 crystal shell, along with pearl sac depositing pearls for ectopic calcification by CaCO3. A total of 48,555 non-coding transcripts were obtained. 229 differentially expressed lncRNAs in mantle tissue as well as 401 differentially expressed lncRNAs in the comparison of mantle center to pearl sac were identified. By cis- and trans-regulation ways, these DELs could be involved in provisioning and metabolism such as chitin, glycosaminoglycan, ECM/shell matrix protein, Ca2+ and HCO3- offering, and also affecting related signaling pathways. In addition, lncRNAs were found to crosstalk with miRNAs not only as primary competing endogenous RNAs but as the primary miRNAs. Our studies provided insight into non-coding RNA regulation of epigenetic regulation in biomineralization in bivalve species.

Alzheimer's disease is a progressive neurodegenerative condition that is the most frequent reason for dementia. Due to the increasing trend of aging in societies, it will place a large social and financial burden on society. Although beta amyloid plaques and the formation of neurofibrillary tangles are mentioned as the main events in this disorder, the exact molecular pathology and inflammatory regulatory networks involved in neuroinflammatory events, as a fundamental pathogenic mechanism remain unknown. Understanding these molecular network pathways in addition to helping to understand the pathogenesis of Alzheimer's disease, can also help in the early diagnosis as well as the control of inflammatory processes that are involved in its progression. So, in this study, we intend to have an overview on the regulatory lncRNAs of Alzheimer's disease and their related miRNA and mRNAs, as well as the relationship of these regulatory pathways with inflammatory processes, so that we can provide a perspective for future studies in the field of diagnosis and possibly treatment of this disorder.

To synthesize the current understanding of RNA-based regulatory mechanisms, focusing on how RNA splicing and non-coding RNAs shape immune responses and airway remodeling in asthma, with the aim of exploring their potential as therapeutic targets for asthma treatment.

Recent advances and emerging research in molecular biology and immunology related to RNA splicing, non-coding RNAs (lncRNAs, circRNAs), and N6-methyladenosine (m6A) RNA methylation in asthma pathogenesis.

The review incorporates studies highlighting the roles of alternative RNA splicing, non-coding RNAs (lncRNAs and circRNAs), and RNA methylation (m6A) in regulating immune and inflammatory pathways involved in asthma.

RNA splicing events, non-coding RNAs, and m6A RNA methylation are critical in modulating immune dysregulation, airway remodeling, and inflammation in asthma. These mechanisms influence key inflammatory pathways, mRNA stability, and the overall immune landscape of the disease.

RNA splicing and non-coding RNAs represent promising areas of research for understanding asthma's immune pathology and hold potential as novel therapeutic targets for more effective treatment strategies.

Peste des petits ruminants virus (PPRV) is an important pathogen that has long been a significant threat to small ruminant productivity worldwide. Iron metabolism is vital to the host and the pathogen. However, the mechanism underlying host-PPRV interactions from the perspective of iron metabolism and iron-mediated membrane lipid peroxidation has not been reported thus far. In this study, we identified a novel host long-noncoding RNA (lncRNA), APR, that impairs PPRV infectivity by sponging miR-3955-5p, a negative microRNA (miRNA) that directly targets the gene encoding the ferritin-heavy chain 1 (FTH1) protein. Importantly, we demonstrated that PPRV infection causes aberrant cellular iron accumulation by increasing transferrin receptor (TFRC) expression and that iron accumulation induces reticulophagy and ferroptosis, which benefits PPRV replication. Moreover, PPRV infection enhanced the localization of cellular iron on the endoplasmic reticulum (ER) and caused ER membrane damage by promoting excess lipid peroxidation to induce reticulophagy. Interestingly, APR decreased PPRV infection-induced accumulation of intracellular Fe2+ via miR-3955-5p/FTH1 axis and ultimately inhibited reticulophagy and ferroptosis. Additionally, our results indicate that interferon regulatory factor 1 promotes APR transcription by positively regulating APR promoter activity after PPRV infection. Taken together, our findings revealed a new pattern of PPRV-host interactions, involving noncoding RNA regulation, iron metabolism, and iron-related membrane lipid peroxidation, which is critical for understanding the host defense against PPRV infection and the pathogenesis of PPRV.IMPORTANCEMany viruses have been demonstrated to engage in iron metabolism to facilitate their replication and pathogenesis. However, the mechanism by which PPRV interacts with host cells from the perspective of iron metabolism, or iron-mediated membrane lipid peroxidation, has not yet been reported. Our data provide the first direct evidence that PPRV infection induces aberrant iron accumulation to promote viral replication and reveal a novel host lncRNA, APR, as a regulator of iron accumulation by promoting FTH1 protein expression. In this study, PPRV infection increased cellular iron accumulation by increasing TFRC expression, and more importantly, iron overload increased viral infectivity as well as promoted ER membrane lipid peroxidation by enhancing the localization of cellular iron on the ER and ultimately induced ferroptosis and reticulophagy. Furthermore, a host factor, the lncRNA APR, was found to decrease cellular iron accumulation by sponging miR-3955-5p, which directly targets the gene encoding the FTH1 protein, thereby attenuating PPRV infection-induced ferroptosis and reticulophagy and inhibiting PPRV infection. Taken together, the results of the present study provide new insight into our understanding of host-PPRV interaction and pathogenesis from the perspective of iron metabolism and reveal potential targets for therapeutics against PPRV infection.

Long Intergenic Non-Protein Coding RNA 1123 (LINC01123), located on human chromosome 2q13, is a pivotal factor in tumorigenesis, exerting multifaceted oncogenic effects. Its expression strongly correlates with clinicopathological features, patient survival, and disease progression. In vivo and in vitro experiments further demonstrate that LINC01123 influences diverse cellular processes, including proliferation, apoptosis, viability, migration, invasion, stemness, and tumor growth. Notably, it also regulates metabolic reprogramming, immune escape, and tumor cell resistance to treatment. LINC01123 is regulated by multiple transcription factors and participates in gene regulation through protein interactions and competitive endogenous RNA (ceRNA) networks, thereby modulating cancer-promoting effects. This work systematically elucidates its primary functions and molecular mechanisms driving cancer initiation and progression, suggesting that LINC01123 might serve as a novel potential oncogenic driver and biomarker in various cancers.

Disuse osteoporosis (DOP) poses a significant health risk during extended space missions. Although the importance of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cells (BMSCs) and orthopedic diseases is recognized, the precise mechanism by which lncRNAs contribute to DOP remains elusive. This research aims to elucidate the potential regulatory role of lncRNAs in DOP.

Sequencing data were obtained from Gene Expression Omnibus (GEO) datasets, including coding and non-coding RNAs. Positive co-expression pairs of lncRNA-mRNA were identified using weighted gene co-expression network analysis, while miRNA-mRNA expression pairs were derived from the prediction database. A mRNA-miRNA-lncRNA network was established according to the shared mRNA. Functional enrichment analysis was conducted for the shared mRNAs using genome ontology and KEGG pathways. Hub genes were identified through protein-protein interaction analysis, and connectivity map analysis was employed to identify potential therapeutic agents for DOP.

Integration of 74 lncRNAs, 19 miRNAs, and 200 mRNAs yielded a comprehensive mRNA-miRNA-lncRNA network. Enrichment analysis highlighted endoplasmic reticulum stress and extracellular matrix (ECM) pathways as significant in the ceRNA network. PPI analysis revealed three hub genes (COL4A1, LAMC1, and LAMA4) and identified five lncRNA-miRNA-hub gene regulatory axes. Furthermore, three potential therapeutic compounds (SB-216763, oxymetholone, and flubendazole) for DOP were identified.

This study sheds light on the involvement of lncRNAs in the pathogenesis and treatment of DOP through the construction of a ceRNA network, linking protein-coding mRNA functions with non-coding RNAs.

Weightless bone loss is a common pathological phenomenon in weightless environments, yet its specific molecular mechanism remain incompletely elucidated. The aim of this study was to systematically investigate the differential expression profiles of mRNAs and long noncoding RNAs (lncRNAs) to explore the molecular pathogenesis underlying weightless bone loss.

Transcriptome sequencing was performed on bone marrow mesenchymal stem cell (BMSCs) samples from the Ground control group and simulated microgravity (SMG) group using Illumina technology. Using the DESeq2 algorithm, we accurately identify and analyzed the differentially expressed genes (DEGs). Subsequently, the molecular functions and signaling pathways enriched by DEG were comprehensively analyzed by GO and KEGG. In addition, by constructing lncRNA-mRNA coexpression network, this study screened and verified key lncRNAs as potential genes to further explore their role in the occurrence and development of weightless bone loss.

A total of 215 differentially expressed lncRNAs (DElncRNAs) and 381 differentially expressed mRNAs (DEmRNAs) were identified, in the SMG group. DEmRNAs were primarily involved in the cell response to mechanical stimulation, microtubule motility and TNF signaling pathway. Meanwhile, DElncRNAs are significantly enriched in cell differentiation, fatty acid metabolic process and biosynthesis of amino acids. In addition, the expression levels of related lncRNAs and mRNAs in weightless bone loss were verified via qRT-PCR. lncRNA-mRNA coexpression network found that lncRNA Ubr5 closely related to osteoblast proliferation and differentiation. Further experimental results revealed that knocking down lncRNA Ubr5 can promote the apoptosis of BMSCs and inhibit their proliferation and osteogenic differentiation.

This study revealed the molecular pathogenesis of weightless bone loss, identified lncRNA Ubr5 as a potential intervention target, and provided an important scientific basis and strategic guidance for the prevention and treatment of weightless bone loss.

Clove (Syzygium aromaticum), valued for its role in food preservation and medicine, has recently drawn research interest for its noncoding RNAs (ncRNAs). This study discovers 3274 long noncoding RNAs (lncRNAs) and 2404 circular RNAs (circRNAs) from publicly available RNAseq data. We identified the regulation of 834 genes through miRNA-lncRNA-mRNA network interactions. Additionally, 35 lncRNAs were predicted as precursors for 17 microRNAs (miRNAs), highlighting their role in post-transcriptional regulation. Tissue-specific analysis of circRNAs revealed their interaction with 1047 miRNAs and competing for binding sites on 2382 messenger RNAs (mRNAs). These results underscore their involvement in complex regulatory networks. To support further research and development, we developed SaroNcRDb (http://backlin.cabgrid.res.in/saroncrdb/), a web resource providing detailed insights into the types, chromosomal locations, tissue distributions, and interactions of identified ncRNAs. The findings pave the way for future studies to harness the regulatory roles of ncRNAs in improving Clove's agronomic traits and secondary metabolite production.

The sea cucumber Apostichopus japonicus, renowned for its remarkable ability to expel and regenerate its internal organs within weeks, serves as a model organism for regeneration research. However, studies on the role of non-coding RNAs, particularly long non-coding RNA (lncRNA), in intestinal regeneration remain limited. In this study, we identified and performed differential expression analysis of lncRNAs in both normal intestines and intestines at 3 days post evisceration (dpe). A total of 2361 lncRNAs were identified, 183 of which were differentially expressed (DE-lncRNAs). The genes targeted by these lncRNAs, either cis- or trans-acting, were involved in oxidative stress, immune response, extracellular matrix remodeling, and energy metabolism during intestinal regeneration. Notably, MSTRG.6200/miR-7847-3p and MSTRG.18440/miR-4220-5p have been confirmed as interacting lncRNA-miRNA pairs. These results suggest that lncRNAs are key regulators of intestinal regeneration in A. japonicus, offering new insights into the underlying mechanisms and potential targets for enhancing regeneration.

Acute kidney injury (AKI), often triggered by ischemia-reperfusion (I/R) injury, is a critical condition characterized by rapid loss of renal function, leading to high morbidity and mortality. Despite extensive research, therapeutic options for ischemic AKI remain limited, and understanding the molecular mechanisms involved is crucial for developing targeted therapies. Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various diseases, including cancer and renal injury. This study investigates the role of the lncRNA MIR22HG in mitigating renal injury during ischemic AKI. Using in vivo and in vitro models of I/R-induced AKI in mice and hypoxia/reoxygenation (H/R)-treated renal cells, we demonstrated that MIR22HG expression is significantly downregulated in ischemic AKI conditions. Functional assays showed that overexpression of MIR22HG in these models led to reduced renal cell apoptosis, inflammation, and improved renal function. Mechanistically, MIR22HG exerted its protective effects by negatively regulating miR-134-5p, which in turn alleviated renal injury by upregulating NFAT5, a transcription factor known to mitigate cellular stress. Furthermore, dual-luciferase and RNA pull-down assays confirmed direct interactions between MIR22HG and miR-134-5p, as well as miR-134-5p and NFAT5. Additionally, loss-and-gain-of-function assays demonstrated that overexpression of MIR22HG led to the upregulation of NFAT5, which mitigated renal apoptosis, and inflammation and improved renal function. Collectively, the results of our study highlight the therapeutic potential of targeting the MIR22HG/miR-134-5p/NFAT5 axis in the treatment of ischemic AKI, providing new insights into the molecular regulation of renal cell survival and repair during injury.

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.

The expression level of long non-coding RNA (lncRNA), which functions in a manner similar to that of microrNA, has been confirmed to be closely associated with the regulatory network of multiple cancers. The primary focus of this particular research endeavor was to elucidate the mechanism of action of LINC01232 within the context of prostate cancer, specifically examining how it influences the proliferation of prostate cancer cells by interacting with the miR-181a-5p/IRS2 pathway. Additionally, the study aimed to delve deeper into the role of the Ki-67 protein within this intricate process. To assess the expression and localization of the Ki-67 protein in prostate cancer cells, researchers employed a combination of immunofluorescence and immunohistochemistry techniques. The expression level of Ki-67 protein decreased significantly after down-regulation of LINC01232, indicating that the cell proliferation activity was inhibited. Immunofluorescence and immunohistochemical experiments further confirmed that the expression of Ki-67 protein in prostate cancer cells was positively correlated with the expression of LINC01232.

Long non-coding RNAs (lncRNAs), a type of non-coding RNA molecules, are known to play critical regulatory roles in various biological processes. However, the functions of the majority of lncRNAs remain largely unknown, and little is understood about the regulation of lncRNA expression. In this study, high-throughput DNA genotyping and RNA sequencing were applied to investigate genomic regions associated with lncRNA expression, commonly referred to as lncRNA expression quantitative trait loci (eQTLs). We analyzed the liver, lung, spleen, and muscle transcriptomes of 100 three-way crossbred sows to identify lncRNA transcripts, explore genomic regions that might influence lncRNA expression, and identify potential regulators interacting with these regions.

We identified 6380 lncRNA transcripts and 3733 lncRNA genes. Correlation tests between the expression of lncRNAs and protein-coding genes were performed. Subsequently, functional enrichment analyses were carried out on protein-coding genes highly correlated with lncRNAs. Our correlation results of these protein-coding genes uncovered terms that are related to tissue specific functions. Additionally, heatmaps of lncRNAs and protein-coding genes at different correlation levels revealed several distinct clusters. An expression genome-wide association study (eGWAS) was conducted using 535,896 genotypes and 1829, 1944, 2089, and 2074 expressed lncRNA genes for liver, spleen, lung, and muscle, respectively. This analysis identified 520,562 significant associations and 6654, 4525, 4842, and 7125 eQTLs for the respective tissues. Only a small portion of these eQTLs were classified as cis-eQTLs. Fifteen regions with the highest eQTL density were selected as eGWAS hotspots and potential mechanisms of lncRNA regulation in these hotspots were explored. However, we did not identify any interactions between the transcription factors or miRNAs in the hotspots and the lncRNAs, nor did we observe a significant enrichment of regulatory elements in these hotspots. While we could not pinpoint the key factors regulating lncRNA expression, our results suggest that the regulation of lncRNAs involves more complex mechanisms.

Our findings provide insights into several features and potential functions of lncRNAs in various tissues. However, the mechanisms by which lncRNA eQTLs regulate lncRNA expression remain unclear. Further research is needed to explore the regulation of lncRNA expression and the mechanisms underlying lncRNA interactions with small molecules and regulatory proteins.

Biofortified maize with enhanced carotenoid content was developed to combat vitamin A deficiency. However, it was observed that during storage, carotenoids present in maize grain get degraded and it has been reported that carotenoid cleavage dioxygenase1 (ccd1) is responsible for this degradation.

In our current study, comprehensive in-silico analysis deciphered a complete overview of the ccd1 gene in maize including the gene structures, phylogeny, chromosomal locations, promoter analysis, conserved motifs and interacting protein partners. In addition to these, a comparative in-silico analysis of the ccd1 gene in maize, rice and Arabidopsis was performed. An intronic region of ccd1, unique to the maize genome, was matched significantly with a lot of long non-coding RNA and was identified. Also, growth stage-specific ccd1 expression analysis was performed in two maize inbred lines, V335PV and HKI161PV. The results indicate that both inbred lines displayed higher ccd1 expression during reproductive stages compared to vegetative stages, with the highest expression level observed at the milking stage in both inbreds.

This detailed in-silico characterisation and expression analysis of the ccd1 gene contributes to our understanding of its activity and expression pattern in maize in stage and tissue-specific manner. This study will further provide an effective strategy for manipulating the ccd1 gene to enhance the carotenoid content of maize grain, thereby aiding in the combat against vitamin A deficiency.

This study aimed to identify splicing quantitative trait loci (cis-sQTL) in Nelore cattle muscle tissue and explore the involvement of spliced genes (sGenes) in immune system-related biological processes. Genotypic data from 80 intact male Nelore cattle were obtained using SNP-Chip technology, while RNA-Seq analysis was performed to measure gene expression levels, enabling the integration of genomic and transcriptomic datasets. The normalized expression levels of spliced transcripts were associated with single nucleotide polymorphisms (SNPs) through an analysis of variance using an additive linear model with the MatrixEQTL package. A permutation analysis then assessed the significance of the best SNPs for each spliced transcript. Functional enrichment analysis was performed on the sGenes to investigate their roles in the immune system. In total, 3,187 variants were linked to 3,202 spliced transcripts, with 83 sGenes involved in immune system processes. Of these, 31 sGenes were enriched for five transcription factors. Most cis-sQTL effects were found in intronic regions, with 27 sQTL variants associated with disease susceptibility and resistance in cattle. Key sGenes identified, such as GSDMA, NLRP6, CASP6, GZMA, CASP4, CASP1, TREM2, NLRP1, and NAIP, were related to inflammasome formation and pyroptosis. Additionally, genes like PIDD1, OPTN, NFKBIB, STAT1, TNIP3, and TREM2 were involved in regulating the NF-kB pathway. These findings lay the groundwork for breeding disease-resistant cattle and enhance our understanding of genetic mechanisms in immune responses.

Endogenous and environmental stressors can damage DNA and RNA to compromise genome and transcriptome stability and integrity in cells, leading to genetic instability and diseases. Recent studies have demonstrated that RNA damage can also modulate genome stability via RNA-templated DNA synthesis, suggesting that it is essential to maintain RNA integrity for the sustainment of genome stability. However, little is known about RNA damage and repair and their roles in modulating genome stability. Current efforts have mainly focused on revealing RNA surveillance pathways that detect and degrade damaged RNA, while the critical role of RNA repair is often overlooked. Due to their abundance and susceptibility to nucleobase damaging agents, it is essential for cells to evolve robust RNA repair mechanisms that can remove RNA damage, maintaining RNA integrity during gene transcription. This is supported by the discovery of the alkylated RNA nucleobase repair enzyme human AlkB homolog 3 that can directly remove the methyl group on damaged RNA nucleobases, predominantly in the nucleus of human cells, thereby restoring the integrity of the damaged RNA nucleobases. This is further supported by the fact that several DNA repair enzymes can also process RNA damage. In this review, we discuss RNA damage and its effects on cellular function, DNA repair, genome instability, and potential RNA damage repair mechanisms. Our review underscores the necessity for future research on RNA damage and repair and their essential roles in modulating genome stability.

Glioblastoma (GB), the most common and aggressive brain tumor, demonstrates intrinsic resistance to current therapies, resulting in poor clinical outcomes. Cancer progression can be partially attributed to the deregulation of protein translation mechanisms that drive cancer cell growth. In this study, we present the translatome landscape of GB as a valuable data resource. Eight patient-derived GB sphere cultures (GSCs) were analyzed using ribosome profiling and messenger RNA (mRNA) sequencing. We investigated inter-cell-line differences through differential expression analysis at both the translatome and transcriptome levels. Translational changes post-radiotherapy were assessed at 30 and 60 min. The translation of non-coding RNAs (ncRNAs) was validated using in-house and public mass spectrometry (MS) data, whereas RNA expression was confirmed by quantitative PCR (qPCR). Our findings demonstrate that ribosome sequencing provides more detailed information than MS or transcriptional analyses. Transcriptional similarities among GSCs correlate with translational similarities, aligning with previously defined subtypes such as proneural and mesenchymal. Additionally, we identified a broad spectrum of open reading frame types in both coding and non-coding mRNA regions, including long non-coding RNAs (lncRNAs) and pseudogenes undergoing active translation. Translation of ncRNAs into peptides was independently confirmed by in-house data and external MS data. We also observed that translational regulation of histones (downregulated) and splicing factors (upregulated) occurs in response to radiotherapy. These data offer new insights into genome-wide protein synthesis, identifying translationally regulated genes and alternative translation initiation sites in GB under normal and radiotherapeutic conditions, providing a rich resource for GB research. Further functional validation of differentially expressed genes after radiotherapy is needed. Understanding translational control in GB can reveal mechanistic insights and identify currently unknown biomarkers, ultimately enhancing the diagnosis and treatment of this aggressive brain cancer.

The oncogenic and tumor suppressor roles of lnc-MAPKAPK5-AS1 in multiple cancers suggest its complexity in modulating cancer progression. The expression and promoter methylation level of lnc-MAPKAPK5-AS1 in hepatocellular carcinoma (HCC) was investigated through data mining from The Cancer Genome Atlas and Gene Expression Omnibus and its significance in prognosis and immunity was explored. lnc-MAPKAPK5-AS1 was co-expressed with its protein-coding gene MAPKAPK5 in HCC and exhibited upregulation in HCC tissues as a result of hypomethylation of its promoter region. High expression of lnc-MAPKAPK5-AS1 was associated with poor prognosis. Enrichment analysis revealed that lnc-MAPKAPK5-AS1 is involved in immune and metabolic-related pathways. Changes in the expression of lnc-MAPKAPK5-AS1 affected plasma cells, T cells CD4+ memory resting, NK cells, macrophages M0/M1, and mast cells resting in the tumor microenvironment. lnc-MAPKAPK5-AS1 was found to correlate with multiple immune checkpoints. Analysis of the Sangerbox database revealed positive relationships between expression of lnc-MAPKAPK5-AS1, tumor mutational burden and microsatellite instability, which suggested that immunotherapy may be effective in tumors with high expression of lnc-MAPKAPK5-AS1. The expression of lnc-MAPKAPK5-AS1 was verified to indicate sensitivity to 16 common targeted drugs. Immunohistochemistry confirmed the expression of MAPKAPK5 protein in HCC and its prognostic significance. Weighted gene co-expression network analysis was applied to identify hub genes related to both immunoreactive score and gene expression. These results revealed that lnc-MAPKAPK5-AS1 may be involved in the occurrence and development of HCC as an oncogene and may represent a potential therapeutic target through modulating the substance metabolism and immune response.

Long non-coding RNAs (lncRNAs) play diverse biological roles within cells. Despite not encoding proteins, they are crucial in regulating gene expression, chromatin structure and function, cell differentiation and development, and the occurrence of diseases. Vibrio alginolyticus (V. alginolyticus) is a common bacterium found in marine environments that poses a threat to shellfish by infecting them through filtration feeding. Research has demonstrated the substantial involvement of lncRNAs in the immune response of shellfish. However, the specific mechanism by which lncRNAs participate in the immune regulatory process following infection of Mytilus coruscus (M. coruscus) with V. alginolyticus has not been investigated. Therefore, the transcription profiles of lncRNAs in M. coruscus hemocytes were investigated. A grand total of 48,246 lncRNAs were detected, with 2421 genes that exhibited and 717 lncRNAs that had differential expression. To gain a better understanding of the potential roles of the differentially expressed lncRNAs (DE-lncRNAs), GO and KEGG pathway analyses were performed on their target mRNAs, suggesting that lncRNAs have the ability to control gene expression levels and consequently influence immune-related pathways, hence regulating the immune response in M. coruscus. Additionally, a total of 138 lncRNA-mRNA pairs were identified through the calculation of co-expression relationships between DE-lncRNAs and immune-related DE-mRNAs. These findings provide new insights into the role of lncRNAs in the immune response of M. coruscus and offer important resources for further investigation into the role of lncRNAs in M. coruscus pathogen infection.

Small nucleolar RNA host gene 10 (SNHG10) is a newly recognized long non-coding RNA (lncRNA) with significant implications in cancer biology. Abnormal expression of SNHG10 has been observed in various solid tumors and hematological malignancies. Research conducted in vivo and in vitro has revealed that SNHG10 plays a pivotal role in numerous biological processes, including cell proliferation, apoptosis, invasion and migration, drug resistance, energy metabolism, immune evasion, as well as tumor growth and metastasis. SNHG10 regulates tumor development through several mechanisms, such as competing with microRNA (miRNA) for binding sites, modulating various signaling pathways, influencing transcriptional activity, and affecting epigenetic regulation. The diverse biological functions and intricate mechanisms of SNHG10 highlight its considerable clinical relevance, positioning it as a potential pan-cancer biomarker and therapeutic target. This review aims to summarize the role of SNHG10 in tumorigenesis and cancer progression, clarify the molecular mechanisms at play, and explore its clinical significance in cancer diagnosis and prognosis prediction, along with its therapeutic potential.

Long noncoding RNAs (lncRNAs) HIF1A-AS2 is upregulated in multiple human cancers and are associated with various aspects of tumor progression. However, the molecular mechanisms of HIF1A-AS2 in cervical cancer (CC) remain largely unknown. In this study, we aim to investigate the expression pattern and signaling pathways of HIF1A-AS2 in CC.

The study included a group of 20 CC patients, from whom tumor tissue specimens were collected. Additionally, three distinct CC cell lines (HeLa, SiHa, CaSki) were utilized. Quantitative real-time PCR (qRT-PCR) was used to assess the transcript levels of HIF1A-AS2 in these samples. Functional studies were performed by CCK-8, Transwell and Apoptosis assays. Databases including JASPAR, miRDB and Targetscan were used for the transcription factor or target miRNA prediction, subsequent dual luciferase activity assay, chromatin immunoprecipitation (ChIP) and Ago2 immunoprecipitation (RIP) were also adopted for validation.

The study demonstrated that HIF1A-AS2 expression was elevated in clinical cervical cancer specimens and cultured cell lines in comparison to normal controls. Knockdown of HIF1A-AS2 notably inhibited the proliferation and invasion of cervical cancer cells, while inducing apoptosis. In contrast, HIF1A-AS2 overexpression promoted cellular proliferation and invasion and suppressed apoptosis. It was also identified that c-Jun functions as a transcription factor, activating HIF1A-AS2 expression. Additionally, HIF1A-AS2 was found to serve as a molecular sponge for miR-34b-5p, negatively regulating its expression. Furthermore, HIF1A-AS2 controlled the expression of radixin (RDX) by sponging the miR-34b-5p pathway.

Our findings indicate that c-Jun-activated HIF1A-AS2 acts as an oncogenic factor in CC by sponging miR-34b-5p to target radixin. These findings suggest that HIF1A-AS2 might be a viable and promising therapeutic target for cervical cancer treatment.

The severe functional impairment and poor prognosis of early-onset schizophrenia (EOS) create a great need to identify effective biomarkers for early diagnosis in young psychiatric patients. Current research indicates a potential link between loss of autophagy function and emotional and behavioral abnormalities in individuals with psychiatric disorders.

This study aimed to explore diagnostic autophagy-related endogenous competitive RNA (ceRNA) networks for EOS patients. The messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) expression profiles were obtained from peripheral blood mononuclear cells of 18 EOS patients and 12 healthy controls (HC). A co-expression analysis was performed between 365 core lncRNAs and 55 differentially expressed autophagy-related genes (ARGs) to identify differentially expressed autophagy-related lncRNAs. Subsequently, five diagnostic autophagy-related lncRNAs were identified as candidate genes to construct a ceRNA regulatory network using least absolute shrinkage and selection operator (LASSO) Cox regression, and receiver operating characteristic (ROC) curve analysis was performed to evaluate their predictive accuracy. Then, putative interactions among lncRNA-microRNAs (miRNAs)-mRNA were determined based on the lncRNASNP2 and TarBase databases.

Three lncRNAs, twenty miRNAs, and ten mRNAs were selected to construct an autophagy-associated ceRNA network associated with EOS occurrence. Through protein-protein interaction network analysis, five hub mRNAs were identified, which exhibited good predictive ability in distinguishing EOS patients from healthy individuals. ROC curve analysis demonstrated that integrating three diagnostic lncRNAs (RP1-135L22.1, RP5-884C9.2, RP11-390F4.3) along with five hub mRNAs (EIF4G1, AKT1, BAX, WIPI2, MAPT) appeared to yield better diagnostic accuracy compared to using either lncRNAs or mRNAs alone. Furthermore, all three diagnostic lncRNAs and five hub mRNAs were positively correlated with at least two types of immune infiltration.

Through transcriptome analysis, we searched for diagnostic autophagy-related ceRNA networks, which provided valuable candidates for the early diagnosis of EOS.

Brain metastases (BMs) are the most common intracranial tumors in adults and the major cause of cancer-related morbidity and mortality. The occurrence of BMs varies according to the type of primary tumors with most frequence in lung cancer, melanoma and breast cancer. Among of them, lung cancer has been reported to have a higher risk of BMs than other types of cancers with 40 ~ 50% of such patients will develop BMs during the course of disease. BMs lead to many neurological complications and result in a poor quality of life and short life span. Although the treatment strategies were improved for brain tumors in the past decades, the prognosis of BMs patients is grim. Poorly understanding of the molecular and cellular characteristics of BMs and the complicated interaction with brain microenvironment are the major reasons for the dismal prognosis of BM patients. Recent studies have enhanced understanding of the mechanisms of BMs. The newly identified potential therapeutic targets and the advanced therapeutic strategies have brought light for a better cure of BMs. In this review, we summarized the mechanisms of BMs during the metastatic course, the molecular and cellular landscapes of BMs, and the advances of novel drug delivery systems for overcoming the obstruction of blood-brain barrier (BBB). We further discussed the challenges of the emerging therapeutic strategies, such as synergistic approach of combining targeted therapy with immunotherapy, which will provide vital clues for realizing the precise and personalized medicine for BM patients in the future.

This study investigated whether m5C-related Long non-coding RNAs (lncRNAs) can predict clear cell renal cell carcinoma (ccRCC) patient prognosis. Co-expression and Cox regression analyses identified 9 prognostic lncRNAs, which were closely associated with tumor immune characteristics and immune escape. The model also predicted the sensitivity of drugs, including Entinostat, SB216763, and Sapitinib. In vitro experiments showed that GNG12-AS1 inhibited ccRCC cell proliferation and migration by reducing the activity of the ERK/GSK-3β/β-catenin pathway. Overall, these findings suggest that the 9 m5C-related lncRNAs can accurately predict ccRCC patient prognosis, providing potential applications for clinical and immunotherapy approaches. GNG12-AS1 emerges as a promising prognostic biomarker for predicting survival outcomes in ccRCC, potentially influencing cell migration through the activation of the ERK/GSK-3β/β-catenin signaling pathway.

Skin cutaneous melanoma (SKCM) is a cancer with serious global impact. Long non-coding RNA was previously found to be associated with tumor prognosis. This research focuses on long intergenic non-protein coding (LINC) RNAs, and correlated protein-coding genes (PCGs), to explore their diagnostic and prognostic value, function and mechanism. Gene expression data was obtained from TCGA and Oncomine for analysis; in total there were 458 cases included in this study. LIN00518 and the 10 most highly correlated PCGs were selected to determine the diagnostic and prognostic value. We undertook bioinformatic analysis with LINC00518 and the prognostic-related PCGs in order to explore their molecular mechanism. The Connectivity Map was carried out for pharmacological target prediction and drug selection. Among the top 10 correlated PCGs, trafficking kinesin protein 2 (TRAK2), epilepsy of progressive myoclonus type 2 gene A (EPM2A) and melanocyte inducing transcription factor (MITF) had significant diagnostic value (all AUC > 0.7, P < 0.05). LINC00518, ras association domain family member 3 (RASSF3), cdk5 and Abl enzyme substrate 1 (CABLES1), kazrin, periplakin interacting protein (KAZN), EF-hand calcium binding domain 5 (EFCAB5) and MITF were significantly associated with prognosis (all adjusted P < 0.05). LINC00518 was associated with cell cycle process, melanogenesis, MAPK signaling pathway, cell division and DNA repair(all P < 0.05). Pharmacological targets analysis suggested results acquired eight potential target drugs. Up-regulation of LINC00518 is significantly associated with poor prognosis. TRAK2, EPM2A and MITF had diagnostic significance. RASSF3, CABLES1, KAZN, EFCAB5 and MITF had prognostic significance. This study provided novel biomarkers for SKCM.

High expression of the myeloid master ETS transcription factor PU.1 drives the development of monocyte/macrophage (Mono/MΦ), a crucial cellular component of the innate immune system. Disruptions in normal expression patterns of PU.1 are linked to a variety myeloid malignancy and immune diseases. It is evidenced that PU.1 binds to and modulates enhancers of several myeloid genes. While noncoding RNAs transcribed from noncoding genes at the enhancers are increasingly reported to be involved in enhancer regulation, the crosstalk between PU.1 and noncoding RNAs in enhancer-mediated myeloid gene regulation in Mono/MΦ differentiation and immune response has not been systematically investigated. In this study, we interrogated the PU.1-mediated transcriptome and cistrome with our comprehensive collection of putative and verified enhancers. Among a repertoire of noncoding genes present at PU.1-bound enhancers, we discovered that PU.1 acts as a potent transcription factor inducer of the noncoding RNA LOUP , which we previously identified as an RNA inducer of PU.1. The genomic region within the LOUP locus occupied by PU.1 is characterized by the epigenetic features of a myeloid-specific super-enhancer. Targeted disruption of the PU.1-binding motifs resulted in the downregulation of LOUP promoter activity. Depletion of LOUP reduced the expression of Mono/MΦ cell markers as well as the transcriptional program associated with Mono/MΦ differentiation Mono/MΦ innate defense mechanisms, including phagocytosis, antimicrobial activity, and chemoattractant cytokine production. LOUP induces Mono/MΦ phagocytic activities. Collectively, our findings indicate that PU.1 and enhancer RNA LOUP are biomolecular components of an unidentified feed-forward loop that promotes their mutual expression, contributing to Mono/MΦ differentiation and innate immune functions. The identification of the PU.1/ LOUP regulatory circuit provides valuable insights into the mechanisms underlying cell-type and gene-specific enhancer activity and Mono/MΦ biology, as well as significant implications for advancing our understanding of immune diseases and myeloid malignancies.

Low-nitrogen (LN) conditions typically promote anthocyanin biosynthesis in plants. Although previous studies primarily explored structural genes and transcription factors involved in anthocyanin biosynthesis, the role of long noncoding RNAs (lncRNAs) in this process under LN conditions remains less understood. This study identified LNC159c as a potential regulator of anthocyanin biosynthesis, with its expression notably downregulated under LN conditions. LNC159c functions as the host gene of miR159c, which regulates its expression. A dual-luciferase reporter assay and GFP signal detection demonstrated that miR159c inhibited MsMYB10 expression through base complementary pairing. Yeast one-hybrid (Y1H) and dual-LUC reporter assays jointly verified that MsMYB10 binds to the F3'H promoter. Stable overexpression in apple calli and transient overexpression in apple fruit peels and M. spectabilis leaves showed that LNC159c overexpression promoted miR159c expression, while inhibiting MsMYB10 expression and anthocyanin biosynthesis. MsMYB10 overexpression promoted anthocyanin biosynthesis, whereas the opposite results were observed in MsMYB10-silenced tissues. Thus, under LN conditions, reduced LNC159c expression limits miR159c production, relieving MsMYB10 inhibition and enhancing anthocyanin accumulation. These findings highlight the regulatory role of lncRNAs in anthocyanin biosynthesis under LN conditions.

Over 400 articles on the pathophysiology of brain aging, neuroaging, and neurodegeneration were reviewed, with a focus on epigenetic mechanisms and numerous non-coding RNAs. In particular, this review the accent is on microRNAs, the discovery of whose pivotal role in gene regulation was recognized by the 2024 Nobel Prize in Physiology or Medicine. Aging is not a gradual process that can be easily modeled and described. Instead, multiple temporal processes occur during aging, and they can lead to mosaic changes that are not uniform in pace. The rate of change depends on a combination of external and internal factors and can be boosted in accelerated aging. The rate can decrease in decelerated aging due to individual structural and functional reserves created by cognitive, physical training, or pharmacological interventions. Neuroaging can be caused by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle, and environmental factors, which are especially noticeable in space environments where adaptive changes can trigger aging-like processes. Numerous candidate molecular biomarkers specific to neuroaging need to be validated to develop diagnostics and countermeasures.

Y RNAs are a class of highly conserved small non-coding RNAs. Emerging evidences reported that Y RNAs and their Y RNA-derived small RNAs (YsRNAs) represent bioactive molecules and not simply structural RNAs involved in scaffolding and assembling. They can interact and regulate both localization and functions of several RNA-binding proteins implicated in a wide range of cellular processes such as DNA replication, RNA quality control and cellular stress responses. More evidences suggest functional involvement of Y RNAs in several type of disease such as cancer, immune related pathologies, neurological disorders and cardiovascular diseases. Nevertheless, there are many questions that still need to be answered for their functional and mechanistic understanding in a physiological and in a pathological context. In this review we will describe the current state of knowledge about YRNAs, their structure, biogenesis, functions and interaction with known proteins, as well their role in disease. The picture arising indicates their potential function as biomarkers for disease diagnosis, as well as therapeutical targets for building up tailored approaches in personalized medicine.

India harbors the world's largest cattle population, encompassing over 50 distinct Bos indicus breeds. This rich genetic diversity underscores the inadequacy of a single reference genome to fully capture the genomic landscape of Indian cattle. To comprehensively characterize the genomic variation within Bos indicus and, specifically, dairy breeds, we aim to identify non-reference sequences and construct a comprehensive pangenome.

Five representative genomes of prominent dairy breeds, including Gir, Kankrej, Tharparkar, Sahiwal, and Red Sindhi, were sequenced using 10X Genomics 'linked-read' technology. Assemblies generated from these linked-reads ranged from 2.70 Gb to 2.77 Gb, comparable to the Bos indicus Brahman reference genome. A pangenome of Bos indicus cattle was constructed by comparing the newly assembled genomes with the reference using alignment and graph-based methods, revealing 8 Mb and 17.7 Mb of novel sequence respectively. A confident set of 6,844 Non-reference Unique Insertions (NUIs) spanning 7.57 Mb was identified through both methods, representing the pangenome of Indian Bos indicus breeds. Comparative analysis with previously published pangenomes unveiled 2.8 Mb (37%) commonality with the Chinese indicine pangenome and only 1% commonality with the Bos taurus pangenome. Among these, 2,312 NUIs encompassing ~ 2 Mb, were commonly found in 98 samples of the 5 breeds and designated as Bos indicus Common Insertions (BICIs) in the population. Furthermore, 926 BICIs were identified within 682 protein-coding genes, 54 long non-coding RNAs (lncRNA), and 18 pseudogenes. These protein-coding genes were enriched for functions such as chemical synaptic transmission, cell junction organization, cell-cell adhesion, and cell morphogenesis. The protein-coding genes were found in various prominent quantitative trait locus (QTL) regions, suggesting potential roles of BICIs in traits related to milk production, reproduction, exterior, health, meat, and carcass. Notably, 63.21% of the bases within the BICIs call set contained interspersed repeats, predominantly Long Interspersed Nuclear Elements (LINEs). Additionally, 70.28% of BICIs are shared with other domesticated and wild species, highlighting their evolutionary significance.

This is the first report unveiling a robust set of NUIs defining the pangenome of Bos indicus breeds of India. The analyses contribute valuable insights into the genomic landscape of desi cattle breeds.

Myocardial dysfunction, characterized by impaired cardiac muscle function, arises from diverse etiologies, including coronary artery disease, myocardial infarction, cardiomyopathies, hypertension, and valvular heart disease. Recent advancements have highlighted the roles of exosomes and non-coding RNAs in the pathophysiology of myocardial dysfunction. Exosomes are small extracellular vesicles released by cardiac and other cells that facilitate intercellular communication through their molecular cargo, including ncRNAs. ncRNAs are known to play critical roles in gene regulation through diverse mechanisms, impacting oxidative stress, fibrosis, and other factors associated with myocardial dysfunction. Dysregulation of these molecules correlates with disease progression, presenting opportunities for therapeutic interventions. This review explores the mechanistic interplay between exosomes and ncRNAs, underscoring their potential as biomarkers and therapeutic agents in myocardial dysfunction. Emerging evidence supports the use of engineered exosomes and modified ncRNAs to enhance cardiac repair by targeting signaling pathways associated with fibrosis, apoptosis, and angiogenesis. Despite promising preclinical results, delivery, stability, and immunogenicity challenges remain. Further research is needed to optimize clinical translation. Understanding these intricate mechanisms may drive the development of innovative strategies for diagnosing and treating myocardial dysfunction, ultimately improving patient outcomes.

A systems medicine understanding of the regulatory molecular circuits that underpin breast cancer is essential for early cancer detection and precision/personalized medicine in clinical oncology. Transcription factors (TFs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) control gene expression and cell biology, and by extension, serve as pillars of the regulatory circuits that determine human health and disease. We report here the development of a regulatory circuit analysis program, miRCuit, constructing 10 different types of regulatory elements involving messenger RNA, miRNA, lncRNA, and TFs. Using the miRCuit, we analyzed expression profiling data from 179 invasive ductal breast carcinoma and 51 normal tissue samples from the Gene Expression Omnibus database. We identified eight circuit types along with two special types of circuits, one of which highlighted the significant roles of lncRNA CASC15, miR-130b-3p, and TF KLF5 in breast cancer development and progression. These findings advance our understanding of the regulatory molecules associated with breast cancer. Moreover, miRCuit offers a new avenue for users to construct circuits from regulatory molecules for potential applications to decipher disease pathogenesis.

Hematophagous female mosquitoes are important vectors of numerous devastating human diseases, posing a major public health threat. Effective prevention and control of mosquito-borne diseases rely considerably on progress in understanding the molecular mechanisms of various life activities, and accordingly, the molecules that regulate the various life activities of mosquitoes are potential targets for implementing future vector control strategies. Many long non-coding RNAs (lncRNAs) have been identified in mosquitoes and significant progress has been made in determining their functions. Here, we present a comprehensive overview of the research advances on mosquito lncRNAs, including their molecular identification, function, and interaction with other non-coding RNAs, as well as their synergistic regulatory roles in mosquito life activities. We also highlight the potential roles of competitive endogenous RNAs in mosquito growth and development, as well as in insecticide resistance and virus-host interactions. Insights into the biological functions and mechanisms of lncRNAs in mosquito life activities, viral replication, pathogenesis, and transmission will contribute to the development of novel drugs and safe vaccines.

Previously considered junk or non-functional, long non-coding RNAs (lncRNAs) have emerged over the past few decades as pivotal components in both physiological and pathological processes, including cancer. Neuroblastoma-associated transcript-1 (NBAT-1) was initially discovered a decade ago as a risk-associated tumor suppressor lncRNA in neuroblastoma (NB). Subsequent studies have consistently demonstrated that NBAT-1 serves as a dedicated tumor suppressor in many cancers. NBAT-1 is significantly downregulated in cancer, which is closely linked to higher histological grades, increased metastasis, and poor survival in cancer patients suggesting NBAT-1's potential as a prognostic biomarker. In this review, we delve into the current body of literature, elucidating the tumor-suppressive roles of NBAT-1 and the underlying regulatory mechanisms in the context of human malignancies. Additionally, we shed light on the mechanisms contributing to the diminished expression of NBAT-1 and its potential as both a prognostic biomarker and a promising therapeutic target in cancer.

Long non-coding RNAs (lncRNAs), once thought to be mere transcriptional noise, are now revealing a hidden code. Recent advancements like ribosome sequencing have unveiled that many lncRNAs harbor small open reading frames and can potentially encode functional micropeptides. Emerging research suggests these micropeptides, not the lncRNAs themselves, play crucial roles in regulating homeostasis, inflammation, metabolism, and especially in breast cancer progression. This review delves into the rapidly evolving computational tools used to predict and validate lncRNA-encoded micropeptides. We then explore the diverse functions and mechanisms of action of these micropeptides in breast cancer pathogenesis, with a focus on their roles in various species. Ultimately, this review aims to illuminate the functional landscape of lncRNA-encoded micropeptides and their potential as therapeutic targets in cancer.

The aging of bone marrow mesenchymal stem cells (BMSCs) impairs bone tissue regeneration, contributing to skeletal disorders. LncRNA NEAT1 is considered as a proliferative inhibitory role during cellular senescence, but the relevant mechanisms remain insufficient. This study aims to elucidate how NEAT1 regulates mitotic proteins during BMSCs aging.

BMSCs were isolated from alveolar bone of human volunteers aged 26-33 (young) and 66-78 (aged). NEAT1 expression and distribution changes during aging process were observed using fluorescence in situ hybridization (FISH) in young (3 months) and aged (18 months) mice or human BMSCs. Subsequent RNA pulldown and proteomic analyses, along with single-cell analysis, immunofluorescence, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP), were conducted to investigate that NEAT1 impairs the nuclear transport of mitotic FGF2 and contributes to BMSCs aging.

We reveal that NEAT1 undergoes significant upregulated and shifts from nucleus to cytoplasm in bone marrow and BMSCs during aging process. In which, the expression correlates with nuclear DNA content during karyokinesis, suggesting a link to mitogenic factor. Within NEAT1 knockdown, hallmarks of cellular aging, including senescence-associated secretory phenotype (SASP), p16, and p21, were significantly downregulated. RNA pulldown and proteomic analyses further identify NEAT1 involved in osteoblast differentiation, mitotic cell cycle, and ribosome biogenesis, highlighting its role in maintaining BMSCs differentiation and proliferation. Notably, as an essential growth factor of BMSCs, Fibroblast Growth Factor 2 (FGF2) directly abundant binds to NEAT1 and the sites enriched with nuclear localization motifs. Importantly, NEAT1 decreased the interaction between FGF2 and Karyopherin Subunit Beta 1 (KPNB1), influencing the nuclear transport of mitogenic FGF2.

Our findings position NEAT1 as a critical regulator of mitogenic protein networks that govern BMSC aging. Targeting NEAT1 might offer novel therapeutic strategies to rejuvenate aged BMSCs.

N6-methyladenosine (m6A) modification plays a crucial role in the regulation of diverse cellular processes influenced by environmental factors. Nevertheless, the involvement of m6A-modified long noncoding RNAs (lncRNAs) in the pathogenesis of lung injury induced by particulate matter (PM) remains largely unexplored.

Here, we establish a mouse model of PM-induced lung injury. We utilized m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) to identify differentially expressed m6A peaks on long non-coding RNAs (lncRNAs). Concurrently, we performed lncRNA sequencing (lncRNA-seq) to determine the differentially expressed lncRNAs. The candidate m6A-modified lncRNAs in the lung tissues of mice were identified through the intersection of the data obtained from these two sequencing approaches.

A total of 664 hypermethylated m6A peaks on 644 lncRNAs and 367 hypomethylated m6A peaks on 358 lncRNAs are confirmed. We use bioinformatic tools to analyze the potential functions and pathways of these m6A-modified lncRNAs, revealing their involvement in regulating inflammation, immune response, and metabolism-related pathways. Three key m6A-modified lncRNAs (lncRNA NR_003508, lncRNA uc008scb.1, and lncRNA ENSMUST00000159072) are identified through a joint analysis of the MeRIP-seq and lncRNA-seq data, and their validation is carried out using MeRIP-PCR and qRT-PCR. Analysis of the coding-non-coding gene co-expression network reveals that m6A-modified lncRNAs NR_003508 and uc008scb.1 participate in regulating pathways associated with inflammation and immune response.

This study first provides a comprehensive transcriptome-wide analysis of m6A methylation profiling in lncRNAs associated with PM-induced lung injury and identifies three pivotal candidate m6A-modified lncRNAs. These findings shed light on a novel regulatory mechanism underlying PM-induced lung injury.

Gastric cancer (GC) remains a prevalent and preventable disease, yet accurate early diagnostic methods are lacking. Exosome non-coding RNAs (ncRNAs), a type of liquid biopsy, have emerged as promising diagnostic biomarkers for various tumours. This study aimed to identify a serum exosome ncRNA feature for enhancing GC diagnosis.

Serum exosomes from patients with GC (n=37) and healthy donors (n=20) were characterised using RNA sequencing, and potential biomarkers for GC were validated through quantitative reverse transcription PCR (qRT-PCR) in both serum exosomes and tissues. A combined diagnostic model was developed using LASSO-logistic regression based on a cohort of 518 GC patients and 460 healthy donors, and its diagnostic performance was evaluated via receiver operating characteristic curves.

RNA sequencing identified 182 candidate biomarkers for GC, of which 31 were validated as potential biomarkers by qRT-PCR. The combined diagnostic score (cd-score), derived from the expression levels of four long ncRNAs (RP11.443C10.1, CTD-2339L15.3, LINC00567 and DiGeorge syndrome critical region gene (DGCR9)), was found to surpass commonly used biomarkers, such as carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and CA72-4, in distinguishing GC patients from healthy donors across training, testing and external validation cohorts, with AUC values of 0.959, 0.942 and 0.949, respectively. Additionally, the cd-score could effectively identify GC patients with negative gastrointestinal tumour biomarkers and those in early-stage. Furthermore, molecular biological assays revealed that knockdown of DGCR9 inhibited GC tumour growth.

Our proposed serum exosome ncRNA feature provides a promising liquid biopsy approach for enhancing the early diagnosis of GC.

Significance: Growing evidence indicates the importance of redox reactions homeostasis, mediated predominantly by reactive oxygen species (ROS) in influencing the development, differentiation, progression, metastasis, programmed cell death, tumor microenvironment, and therapeutic resistance of cancer. Therefore, reviewing the ROS-linked epigenetic changes in cancer is fundamental to understanding the progression and prevention of cancer. Recent Advances: We review in depth the molecular mechanisms involved in ROS-mediated epigenetic changes that lead to alteration of gene expression by altering DNA, modifying histones, and remodeling chromatin and noncoding RNA. Critical Issues: In cancerous cells, alterations of the gene-expression regulatory elements could be generated by the virtue of imbalance in tumor microenvironment. Various oxidizing agents and mitochondrial electron transport chain are the major pathways that generate ROS. ROS plays a key role in carcinogenesis by activating pro-inflammatory signaling pathways and DNA damage. This loss of ROS-mediated epigenetic regulation of the signaling pathways may promote tumorigenesis. We address all such aspects in this review. Future Directions: Developments in this growing field of epigenetics are expected to contribute to further our understanding of human health and diseases such as cancer and to test the clinical applications of redox-based therapy. Recent studies of the cancer-epigenetic landscape have revealed pervasive deregulation of the epigenetic factors in cancer. Thus, the study of interaction between ROS and epigenetic factors in cancer holds a great promise in the development of effective and targeted treatment modalities. Antioxid. Redox Signal. 00, 000-000.