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Abstract Background Acute myocardial infarction (AMI) is a cardiovascular disease with the highest morbidity and mortality rate in the world. Several studies have suggested that abnormal regulation of non-coding RNAs (ncRNAs) may play a vital role in the occurrence and progress of AMI. Objective The purpose of this study was to investigate the clinical values of human leukocyte antigen complex group 11 (HCG11) or miR-532-3p in the diagnosis and prognosis of patients with AMI after percutaneous coronary intervention (PCI). Methods The clinical data of 100 AMI patients who underwent PCI were analyzed retrospectively. According to whether major adverse cardiovascular events (MACE) occurred after PCI, they were divided into MACE group (n = 38) and non-MACE group (n = 62). Basic clinical data and serum HCG11 and miR-532-3p levels were analyzed. Multivariate Cox regression analysis was performed to evaluate the risk factors for MACE, and the receiver operator characteristic (ROC) curve was constructed to assess the clinical predictive value of HCG11 and miR-532-3p for MACE. Results Compared with the control group, the serum HCG11 level and miR-532-3p in AMI patients were significantly increased or decreased, and the serum levels of HCG11 and miR-532-3p in the MACE group were significantly increased and decreased, compared with those in non-MACE group. Multivariate Cox regression showed that HCG11 and miR-532-3p were risk factors for MACE occurrence. ROC curve investigated that HCG11 combined with miR-532-3p has accurate predictive value for MACE. Conclusion This study showed that serum HCG11 and miR-532-3p have certain predictive value for MACE after PCI in patients with AMI.

Abstract Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding RNA molecules, including microRNAs and long non-coding RNAs, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding RNAs modulate the response to metformin in cancer cells. The regulatory roles of non-coding RNAs, particularly miRNAs, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncRNAs in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncRNAs. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncRNAs, and this review highlights the mechanisms of non-coding RNA regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding RNAs, offering novel opportunities for the development of personalized treatment strategies in cancer patients.

Abstract Aims The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non‐coding RNAs (lncRNAs) in EAT that might modulate HFpEF development. Methods RNA sequencing (RNA‐seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real‐time PCR (qRT‐PCR). Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of differentially expressed RNAs was performed to predict enriched functions. Results HFpEF patients had higher EAT thickness and NT‐proBNP levels than the control group. A total of 64 471 transcripts were detected including 35 395 protein‐coding sequences, corresponding to 16 854 genes in EAT. RNA‐seq identified a total of 741 dysregulated mRNA transcripts (394 up‐regulated and 347 down‐regulated) and 334 differentially expressed lncRNA transcripts (222 up‐regulated and 112 down‐regulated) in the HFpEF group compared with the control group (P

Background/purpose: The long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) exhibits diverse and complicated functions in cancer progression. Despite reports suggesting both tumor-suppressive and oncogenic effects in various cancers, its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study aimed to investigate the association between NEAT1 expression levels and survival outcomes in HNSCC patients. Materials and methods: Paired tissue samples of tumor and non-cancerous matching tissues (NCMT) from 92 HNSCC patients were collected. NEAT1 expression was analyzed using RT-qPCR. Clinical characteristics, treatment received, and survival rates of the patients were assessed to determine the correlation with NEAT1 expression and explore its association with alcohol, betel quid, and cigarette use. Additionally, we examined the effect of arecoline on NEAT1 expression in normal human oral keratinocytes (NHOK) and fibroblasts (NHOF). Results: The study revealed a significant downregulation of NEAT1 expression in oral cancer tissues compared to NCMT. Meanwhile, arecoline increased NEAT1 expression in NHOK and NHOF cells. However, patients with downregulated NEAT1 expression exhibited higher overall survival rates, particularly in those who did not receive chemotherapy or radiotherapy. Conclusion: NEAT1 expression levels are associated with survival outcomes in HNSCC patients, with upregulated expression indicating a worse prognosis, suggesting this lncRNA might contribute to cancer aggressiveness, especially in the absence of active treatment. These findings indicate NEAT1 may serve as a potential prognostic biomarker in HNSCC, but further research is required to elucidate its role in cancer progression and its potential as a therapeutic target.

In eukaryotes, RNA molecules called long non-coding RNAs (LncRNAs) have been found. Molecules that exceed 200 base pairs in length are incapable of coding for proteins. Studying the function of LncRNAs in cancer has been the main focus of the current investigation, which has significantly impacted protein integrity and stability. LncRNAs can be regulated through various pathways, leading to chromatin changes and methylation or as miRNA sponges. The most common type of liver tumor worldwide is hepatocellular carcinoma (HCC), accounting for around 80 ​% of subjects. Nonetheless, the insufficiency of trustworthy molecular markers remains a significant challenge in HCC diagnosis and treatment evaluation. In HCC, LncRNAs such as MEG3, MALAT1, HULC, HOTAIR, and H19 dysregulation are closely associated with tumor expansion, metastasis, prognosis, and diagnosis. The primary goal of this investigation was to investigate the newly discovered roles and molecular mechanisms of LncRNAs in the pathophysiology of HCC cells to identify potential therapeutic targets.

Abstract Background Parkinson’s disease is the second most common age-related neurodegenerative disease after Alzheimer’s. Pathogenic factors in Parkinson’s include inflammation and oxidative stress, which lead to dopaminergic cell apoptosis. The case–control study aims to determine the expression level of long non-coding RNAs (lncRNAs) of the apoptosis pathway in Parkinson’s patients compared to healthy individuals. In the case–control study, 50 patients with Parkinson’s disease were examined, along with 50 healthy individuals matched in age and sex. In both groups, the expression of long non-coding RNAs, including taurine upregulated 1 (TUG1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), and growth arrest-specific 5 (GAS5), was compared using real-time polymerase chain reaction (PCR). Results The ratio of MALAT1, NEAT1, and TUG1 gene expression in the case group was statistically significantly higher than in healthy individuals. The ratio of GAS5 gene expression in people with Parkinson’s disease was lower, with a statistically significant difference. The ratio of HULC gene expression was higher in the case group, but it did not show a statistically significant difference with the control group. Conclusion The involvement of long lncRNAs that increase apoptosis may play a role in the pathogenesis of the disease, which may be used for identification and therapeutic purposes.

Abstract Background Long non-coding RNAs (lncRNAs) are a distinct class of RNAs with longer than 200 base pairs that are not translated into proteins. Small Nucleolar RNA Host Gene 3 (SNHG3) is a lncRNA and frequently dysregulated in various human cancers. Objective This review provides a comprehensive analysis of current research on lncRNA SNHG3, focusing on its role within the competitive endogenous RNA (ceRNA) network and its implications in cancer. Methods A systematic literature review was conducted using PubMed up to October 2023. The search strategy included keywords such as “lncRNA SNHG3”, “competitive endogenous RNA”, “cancer”, and related terms. Studies were selected based on relevance to SNHG3's involvement in cancer pathogenesis and progression. Results Disruptions in the ceRNA network involving lncRNA SNHG3 can impair normal cell growth and differentiation, significantly contributing to disease pathogenesis, particularly cancer. This review highlights SNHG3's substantial impact on various cancer processes and its potential as a diagnostic and therapeutic tool for aggressive cancers. Conclusion The findings underscore SNHG3's pivotal role in cancer prevention, diagnosis, and treatment, laying a foundation for future research in cancer management. Insights from this review emphasize the necessity for further exploration and development of SNHG3-based diagnostic and therapeutic strategies.

Abstract Disulfidptosis, the newest form of programmed cell death, is closely associated with the immune microenvironment of cancer cells. Long non-coding RNA (lncRNA) has also been found to play a crucial role in melanoma. However, the role of disulfidptosis-related lncRNA in melanoma remains unclear. Through bioinformatic analysis of the transcriptional, clinical, and pathological data from the TCGA-SKCM (The Cancer Genome Atlas—Skin cutaneous melanoma) database, we established a 2-Disulfidptosis-related lncRNA (DRL) prognostic model and a novel molecular subtype for melanoma. The survival and ROC curves of the 2-DRL prognostic model demonstrated its strong efficacy in predicting the prognosis of melanoma. The high-risk group of melanoma exhibited a significant decrease in ESTIMATEScore, ImmuneScore, and StromalScore, indicative of pronounced immune suppression and exhaustion. Subgroup C2 of melanoma displayed an immune-activated state, while subgroups C1 and C3 showed immune suppression and exhaustion, potentially leading to poorer prognosis. Subgroup C1 demonstrated better sensitivity to Zoledronate, UMI-77, Nilotinib, and Cytarabine. Subgroup C2 exhibited greater sensitivity to Ribociclib, XAV939, Topotecan, and Ruxolitinib. Subgroup C3 showed higher sensitivity to VX-11e, Ulixertinib, Trametinib, and Afatinib. This study revealed the immune microenvironment status and targeted drug sensitivity in melanoma patients with different risk scores and molecular subtypes, offering valuable guidance for clinical treatment and identifying significant DRL targets for future in-depth research.

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

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

Background and purpose: Long non-coding RNA (lncRNA) LINC01410, with a length of 647 bp, participates in a variety of tumor biological processes. However, the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma (ESCC) remain unclear. This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion, to provide a potential prognostic indicator and therapeutic target for individuals with ESCC. Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas (TCGA). Gene Set Enrichment Analysis (GSEA) was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC. A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected. This project has been approved by the Hospital Ethics Committee (First Affiliated Hospital of Xinxiang Medical College, No. 2018036; First People's Hospital of Pingdingshan City, No. 2019-018). The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410. Stable transfected cells (EC109/NC, EC109/OE, EC9706/NC and EC9706/KD) were selected in primary cell culture medium containing puromycin. The expression of LINC01410 was detected by RTFQ-PCR. The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay. T cell factor/lymphoid enhancer factor 1 (TCF/LEF1) luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway. The expressions of Wnt/β-catenin and epithelial-mesenchymal transition (EMT) signal pathway related proteins in ESCC cells were detected by Western blot. Results: By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2, we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues (P

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

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

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

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

AIM: To characterize the N6-methyladenosine (m6A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract (ARC). METHODS: Anterior capsule of the lens were collected from patients with CC and ARC. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs. RESULTS: Large amount of m6A peaks within lncRNA were identified for both CC and ARC, while the level was much higher in ARC (49 870 peaks) than that in CC (18 688 peaks), yet those difference between ARC in younger age group (ARC-1) and ARC in elder age group (ARC-2) was quite slight. A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs, as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC. On the other hand, 5893 hypermethylated and 5213 hypomethylated lncRNAs, as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1. Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles, as well as nucleotide excision repair. CONCLUSION: Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC, providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

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

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

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

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

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

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

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

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

Juan Bu,1 Yeledan Mahan,1 Yanmin Zhang,2 Shengnan Zhang,1 Xuanxia Wu,1 Xiaoling Zhang,1 Ling Zhou1 1Medical and Translational Research Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Scientific Research and Education Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Ling Zhou, Medical and Translational Research Center, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Tianshan District, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86 991 8562 317, Email zlrmyy@sina.comBackground: Acacetin is a natural flavonoid known for its anti-tumor, antioxidant, and anti-inflammatory properties. Our previous studies have shown its protective effects against cerebral ischemia-reperfusion injury (IRI), but the underlying molecular mechanisms remain unclear.Purpose: The study delves into acacetin’s mechanism in mitigating cerebral IRI, with a focus on transcriptomic insights.Methods: We established the oxygen-glucose deprivation/re-oxygenation (OGD/R) model in BV2 microglia, treating them with 10μM acacetin. Then we assessed cell proliferation using CCK-8 and measured Lactate Dehydrogenase (LDH) release. High-throughput RNA sequencing (RNA-seq) underpinned the analysis of differentially expressed genes (DEGs) and long non-coding RNAs (lncRNAs), functional enrichment, and alternative splicing events (ASEs), validated by reverse transcription–quantitative polymerase chain reaction (RT-qPCR).Results: OGD/R injury significantly impaired cell proliferation and increased LDH release, effects mitigated by acacetin. RNA-seq identified 2148 upregulated and 2135 downregulated DEGs post-OGD/R. In contrast, the acacetin-treated group showed 248 upregulated and 240 downregulated DEGs compared to the OGD/R group. All DEGs were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Overlapping analysis indicated that acacetin treatment reversed the expression of 203 genes affected by OGD/R, including inflammation-related genes such as Isg15, Fcgr1, Il1b, and Parp12. Moreover, the oxidative stress-related gene, Mt2, was downregulated post-OGD/R but upregulated following acacetin treatment. We further found that OGD/R and acacetin treatment could modulate gene splicing events, impacting cell apoptosis or inflammatory responses, such as the A3SS splicing event in the Trim47 gene. RNA-seq also highlighted differential expression of numerous lncRNAs, particularly the upregulation of lncRNA Rmrp and Terc post-OGD/R and their subsequent downregulation post-acacetin treatment. These lncRNAs might regulate cell proliferation through mediating target gene expressions. RT-qPCR validation confirmed these findings.Conclusion: Significant upregulation of genes and ASEs linked to oxidative stress and inflammatory response is observed in cerebral IRI. Acacetin intervention reverses these effects, highlighting its mechanism in alleviating the injury by modulating gene expression and splicing events.Keywords: acacetin, ischemic stroke, inflammation, genome-wide analysis, differentially expressed genes, alternative splicing, long non-coding RNA, RNA sequencing

Objective Utilizing a specially engineered miR-144-GFP-H1 human embryonic stem cell (hESC) reporter line, this study leverages GFP fluorescence as an indicator of miR-144 expression to gauge the progression of erythropoiesis. The investigation is aimed at elucidating the potential roles of lncRNAs within the erythropoietic framework and conducting an initial assessment of their functional impact. Methods The miR-144/451-GFP-H1 cell line (hereafter referred to as 144-H1) was utilized for in vitro erythrocyte induction culture. The subpopulations of cells entering the erythropoiesis stage were characterized by the surface molecules CD71 and GPA. The GFP reporter gene of miR-144 served as a critical determinant to distinguish between GFP-positive cells (with a high propensity for erythropoiesis) and GFP-negative cells (with a low propensity for erythropoiesis). Transcriptome sequencing was performed on both groups to identify differentially expressed long non-coding RNAs (lncRNAs). LncRNA entries with potential for validation were selected for preliminary functional verification. The CRISPR/Cas9 gene editing technique was employed to design functional interference strategies for the targeted lncRNAs, obtaining 144-H1 cell lines with knocked-out function of the specific lncRNAs. These knockout cell lines, along with non-knockout 144-H1 cell lines, were used for parallel erythrocyte induction culture to identify differential nodes. This approach preliminarily verified their impact on erythropoiesis in an in vitro development model. Results 1)The constructed 144-H1 cell line was capable of expressing GFP fluorescence upon entering the stage of in vitro erythrocyte induction, indicating the activation of miR-144/451. 2)Within the CD71, GPA double-positive group, significant differences in lncRNA expression were observed between the GFP-positive and GFP-negative subpopulations. 3) Gene editing strategies involving the deletion of sequence segments capable of effectively interfering with the function of multiple lncRNA entries were designed and verified for successful editing. In the knockout cell lines, parts of the lncRNA sequences were directly deleted. 4)In parallel validation experiments of erythrocyte induction culture, cell lines with LINC01569 knocked out exhibited significant differences in flow cytometric subpopulations and cell proliferation capabilities compared to the non-knockout cell lines: ①The knockout cell lines showed sustained high expression of GFP fluorescence. ②The proportion of the CD71-GPA double-positive group in the knockout cell lines continuously decreased during erythrocyte maturation. ③No significant expression of hemoglobin was observed in the knockout cell lines, lacking the characteristic red color. ④The cell proliferation capability of the knockout cell lines was significantly lower than that of the non-knockout cell lines (P

Abstract Purpose This study aimed to construct an m6A and cuproptosis-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using the information acquired from The Cancer Genome Atlas (TCGA) database. Methods First, the co-expression analysis was performed to identify lncRNAs linked with N6-methyladenosine (m6A) and cuproptosis in ccRCC. Then, a model encompassing four candidate lncRNAs was constructed via univariate, least absolute shrinkage together with selection operator (LASSO), and multivariate regression analyses. Furthermore, Kaplan–Meier, principal component, functional enrichment annotation, and nomogram analyses were performed to develop a risk model that could effectively assess medical outcomes for ccRCC cases. Moreover, the cellular function of NFE4 in Caki-1/OS-RC-2 cultures was elucidated through CCK-8/EdU assessments and Transwell experiments. Dataset outcomes indicated that NFE4 can have possible implications in m6A and cuproptosis, and may promote ccRCC progression. Results We constructed a panel of m6A and cuproptosis-related lncRNAs to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. Furthermore, the m6A and cuproptosis-related lncRNA model indicated higher diagnostic efficiency than other clinical features. Moreover, the NFE4 function analysis indicated a gene associated with m6A and cuproptosis-related lncRNAs in ccRCC. It was also revealed that the proliferation and migration of Caki-1 /OS-RC-2 cells were inhibited in the NFE4 knockdown group. Conclusion Overall, this study indicated that NFE4 and our constructed risk signature could predict outcomes and have potential clinical value.

Qiang Wang,* Pinduan Bi,* Ding Luo, Pingli Cao, Weihong Chen, Bin Yang Department of Hepatobiliary Surgery, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Yang, Department of Hepatobiliary Surgery, the First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Wuhua District, Kunming, People’s Republic of China, Tel +86 013987642890, Email yangbin@kmmu.edu.cnBackground: Gallstone disease (GS) is an important risk factor for Gallbladder cancer (GBC). However, the mechanisms of the progression of GS to GBC remain unclear. Long non-coding RNA (lncRNA), modulates DNA/RNA/proteins at epigenetic, pre-transcriptional, transcriptional and posttranscriptional levels, and plays a potential therapeutic role in various diseases. This study aims to identify lncRNAs that have a potential impact on GS-promoted GBC progression.Methods and Results: Six GBC patients without GS, six normal gallbladder tissues, nine gallstones and nine GBC patients with GS were admitted to our hospital. The next-generation RNA-sequencing was performed to analyze differentially expressed (DE) lncRNA and messenger RNA (mRNA) in four groups. Then overlapping and specific molecular signatures were analyzed. We identified 29 co-DEGs and 500 co-DElncRNAs related to gallstone or GBC. The intersection and concatenation of co-DEGs and co-DElncRNA functionally involved in focal adhesion, Transcriptional misregulation in cancers, Protein digestion and absorption, and ECM-receptor interaction signaling pathways may contribute to the development of gallbladder cancer. Further exploration is necessary for early diagnosis and the potential treatment of GBC. FXYD2, MPZL1 and PAH were observed in both co-DEGs and co-DElncRNA and validated by qRT-PCR.Conclusion: Our data identified a series of DEGs and DElncRNAs, which were involved in the progression of GBC and GS-related metabolism pathways. Compared to GBC, the GS profile was more similar to para-tumor tissues in transcriptome level and lower risk of cancer. Further exploration is necessary from GBC patients with different periods of follow-up gallstone.Keywords: gallstone, gallbladder cancer, long non-coding RNA, next-generation sequencing analysis, computational biology

Abstract Motivation Long non-coding RNAs (lncRNAs) are a class of molecules involved in important biological processes. Extensive efforts have been provided to get deeper understanding of disease mechanisms at the lncRNA level, guiding towards the detection of biomarkers for disease diagnosis, treatment, prognosis and prevention. Unfortunately, due to costs and time complexity, the number of possible disease-related lncRNAs verified by traditional biological experiments is very limited. Computational approaches for the prediction of disease-lncRNA associations allow to identify the most promising candidates to be verified in laboratory, reducing costs and time consuming. Results We propose novel approaches for the prediction of lncRNA-disease associations, all sharing the idea of exploring associations among lncRNAs, other intermediate molecules (e.g., miRNAs) and diseases, suitably represented by tripartite graphs. Indeed, while only a few lncRNA-disease associations are still known, plenty of interactions between lncRNAs and other molecules, as well as associations of the latters with diseases, are available. A first approach presented here, NGH, relies on neighborhood analysis performed on a tripartite graph, built upon lncRNAs, miRNAs and diseases. A second approach (CF) relies on collaborative filtering; a third approach (NGH-CF) is obtained boosting NGH by collaborative filtering. The proposed approaches have been validated on both synthetic and real data, and compared against other methods from the literature. It results that neighborhood analysis allows to outperform competitors, and when it is combined with collaborative filtering the prediction accuracy further improves, scoring a value of AUC equal to 0966. Availability Source code and sample datasets are available at: https://github.com/marybonomo/LDAsPredictionApproaches.git

Abstract The plant genome exhibits a significant amount of transcriptional activity, with most of the resulting transcripts lacking protein-coding potential. Non-coding RNAs play a pivotal role in the development and regulatory processes in plants. Long non-coding RNAs (lncRNAs), which exceed 200 nucleotides, may play a significant role in enhancing plant resilience to various abiotic stresses, such as excessive heat, drought, cold, and salinity. In addition, the exogenous application of chemicals, such as abscisic acid and salicylic acid, can augment plant defense responses against abiotic stress. While how lncRNAs play a role in abiotic stress tolerance is relatively well-studied in model plants, this review provides a comprehensive overview of the current understanding of this function in horticultural crop plants. It also delves into the potential role of lncRNAs in chemical priming of plants in order to acquire abiotic stress tolerance, although many limitations exist in proving lncRNA functionality under such conditions.

Abstract The identification of novel screening tools is imperative to empower the early detection of colorectal cancer (CRC). The influence of the long non-coding RNA maternally expressed gene 3 (MEG3) rs941576 single nucleotide polymorphism on CRC susceptibility remains uninvestigated. This research appraised MEG3 rs941576 association with the risk and clinical features of CRC and obesity-related CRC and its impact on serum MEG3 expression and its targets miR-27a/insulin-like growth factor 1 (IGF1)/IGF binding protein 3 (IGFBP3) and miR-181a/sirtuin 1 (SIRT1), along with the potential of these markers in obesity-related CRC diagnosis. 130 CRC patients (60 non-obese and 70 obese) and 120 cancer-free controls (64 non-obese and 56 obese) were enrolled. MEG3 targets were selected using bioinformatics analysis. MEG3 rs941576 was associated with magnified CRC risk in overall (OR (95% CI) 4.69(1.51–14.57), P = 0.0018) and stratified age and gender groups, but not with obesity-related CRC risk or MEG3/downstream targets’ expression. Escalated miR-27a and IGFBP3 and reduced IGF1 serum levels were concomitant with MEG3 downregulation in overall CRC patients versus controls and obese versus non-obese CRC patients. Serum miR-181a and SIRT1 were upregulated in CRC patients versus controls but weren’t altered in the obese versus non-obese comparison. Serum miR-181a and miR-27a were superior in overall and obesity-related CRC diagnosis, respectively; meanwhile, IGF1 was superior in distinguishing obese from non-obese CRC patients. Only serum miR-27a was associated with obesity-related CRC risk in multivariate logistic analysis. Among overall CRC patients, MEG3 rs941576 was associated with lymph node (LN) metastasis and tumor stage, serum MEG3 was negatively correlated with tumor stage, while SIRT1 was correlated with the anatomical site. Significant correlations were recorded between MEG3 and anatomical site, SIRT1 and tumor stage, and miR-27a/IGFBP3 and LN metastasis among obese CRC patients, while IGF1 was correlated with tumor stage and LN metastasis among non-obese CRC patients. Conclusively, this study advocates MEG3 rs941576 as a novel genetic marker of CRC susceptibility and prognosis. Our findings accentuate circulating MEG3/miR-27a/IGF1/IGFBP3, especially miR-27a as valuable markers for the early detection of obesity-related CRC. This axis along with SIRT1 could benefit obesity-related CRC prognosis.

Osteosarcoma (OS) is a malignancy characterized by the proliferation of osteoblasts that predominantly affects pediatric and adolescent populations. At present, early detection of OS is significantly lacking, coupled with treatment challenges such as high recurrence rates, increased side effects, and the development of drug resistance. Therefore, developing new diagnostic and therapeutic modalities is clinically significant. Exosomes are naturally occurring nanoparticles found in the body that contain various materials, including DNA, RNA, and proteins. Owing to their numerous beneficial properties, including histocompatibility and in vivo stability, they can be useful as drug carriers. With the development of competitive endogenous non-coding RNA (ncRNA) networks, the role of ncRNA in OS cell control has been increasingly studied. This review provides a thorough summary of multiple potential biogenetic pathways of different ncRNAs in exosomes, including microRNAs, long ncRNAs, and circular RNAs. Moreover, the review highlights their effects on OS cells and their potential applications in the diagnosis, treatment, and control of OS drug resistance. The interplay between different types of ncRNAs, which collectively affect OS through the networks of competing endogenous ncRNAs, is the primary focus of this research.

ABSTRACT Pulmonary cryptococcosis is a common complication in immunocompromised patients. In a mouse model of pulmonary cryptococcosis, Cryptococcus neoformans induces a type 2 immune response that is detrimental to host protection. Long non-coding RNAs (lncRNAs) have emerged as key players in the pathogenesis of infectious diseases. However, the roles and mechanisms of lncRNAs in fungal infection are largely elusive. In the present study, we aimed to explore the roles of LincR-PPP2R5C in pulmonary cryptococcosis. We observed an increase in the level of LincR-PPP2R5C in the lung tissues of C57BL/6J mice after tracheal infection with C. neoformans. Subsequently, we intratracheally infected LincR-PPP2R5C knockout (KO) mice and wild-type mice with C. neoformans. LincR-PPP2R5C deficiency mitigates C. neoformans infection, which can be demonstrated by extending survival time and decreasing fungal burden in the lung. In the lung tissues of infected LincR-PPP2R5C KO mice, there was a notable increase in the levels of type 2 cytokines [interleukin (IL)-4 and IL-5] and an increase in the number of neutrophils in both the lung tissue and bronchoalveolar lavage fluid. Mechanistically, the lack of LincR-PPP2R5C results in increased protein phosphatase 2A phosphorylation, thereby enhancing the fungicidal activity of neutrophils against Cryptococcus neoformans, with IL-4 playing a synergistic role in this process. Overall, LincR-PPP2R5C deficiency mitigated pulmonary cryptococcosis by increasing the fungicidal activity of neutrophils, which was associated with increased IL-4 levels. Our study presented specific evidence of the role of host-derived lncRNAs in the regulation of C. neoformans infection.IMPORTANCEPulmonary cryptococcosis is a human fungal disease caused by Cryptococcus neoformans, which is common not only in immunocompromised individuals but also in patients with normal immune function. Therefore, studying the control mechanisms of pulmonary cryptococcosis is highly important. Here, we demonstrated that the deletion of LincR-PPP2R5C leads to increased killing of C. neoformans by neutrophils, thereby reducing pulmonary cryptococcal infection. These findings will greatly enhance our understanding of the mechanisms by which lncRNAs regulate the pathogenesis of C. neoformans, facilitating the use of lncRNAs in pulmonary cryptococcosis therapy.

Diabetic wound healing is a complex physiological process often hindered by the underlying metabolic dysfunctions associated with diabetes. Despite existing treatments, there remains a critical need to explore innovative therapeutic strategies to improve patient outcomes. This article comprehensively examines the roles of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating key phases of the wound healing process: inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Through a deep review of current literature, we discuss recent discoveries of ncRNAs that have been shown to either promote or impair the wound healing process in diabetic wound healing, which were not covered in earlier reviews. This review highlights the specific mechanisms by which these ncRNAs impact cellular behaviors and pathways critical to each healing stage. Our findings indicate that understanding these recently identified ncRNAs provides new insights into their potential roles in diabetic wound healing, thereby contributing valuable knowledge for future research directions in this field.

Endoplasmic reticulum stress (ERS) and cuproptosis have remarkable effects on hepatocellular carcinoma (HCC) leading to a poor prognosis. The current study aimed to explore credible signature for predicting the prognosis of HCC based on ERS and cuproptosis-related lncRNAs. In our study, clinical and transcriptomic profiles of HCC patients were obtained from the Cancer Genome Atlas (TCGA) database. An ERS and cuproptosis-related lncRNA prognostic signature, including NRAV, SNHG3, LINC00839 and AC004687.1, was determined by correlation tests, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) methods. Survival and predictive value were evaluated using Kaplan–Meier and receiver operating characteristic (ROC) curves, while calibration and nomograms curves were developed. Besides the enrichment analyses for ERS and cuproptosis-related lncRNAs, mutational status and immune status were assessed with TMB and ESTIMATE. Additionally, consensus cluster analysis was employed to compare cancer subtype differences, while drug sensitivity and immunologic efficacy were evaluated for further exploration. qRT-PCR and CCK-8 were utilized to verify the alteration of the prognostic lncRNAs expression and proliferation in vitro. High-risk groups exhibited poorer prognosis. The signature exhibited robust predictive value as an independent prognostic indicator and showed significant correlation with clinicopathological features. In the enriched analysis, biological membrane pathways were enriched. Low-risk patients had lower TMB and higher immune status. A cluster analysis revealed that cluster 2 had the best clinical immunological efficacy and most active immune function. In brief, our constructed signature with ERS and cuproptosis-related lncRNAs was associated survival outcomes of HCC, and can be used to predict the clinical classification and curative effect.

INTRODUCTION AND PURPOSE: Long non-coding RNAs are key regulators of gene expression and tumorigenesis. Deleted in leukemia 1 (DLEU1) is significant in cancer development. This article reviews DLEU1's role across cancers, assessing its diagnostic and therapeutic potential. METHODS: A review of scientific articles from PubMed and Google Scholar was conducted. DESCRIPTION OF THE STATE OF KNOWLEDGE: DLEU1 drives tumor growth in glioblastoma, esophageal, colorectal, and oral cancers by interacting with key miRNAs and genes, promoting malignancy. In breast and ovarian cancers, DLEU1 modulates migration and invasion via specific pathways. In cervical cancer, DLEU1 is linked to immune modulation and serves as a prognostic marker. SUMMARY: DLEU1 is a vital regulator in various cancers, offering potential as a diagnostic and therapeutic target.

Breast cancer (BC) is one of the frequent tumors that seriously endanger the physical and mental well-being in women with strong heterogeneity, and its pathogenesis involves multiple risk factors. Depending on the type of BC, hormonal therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Despite significant progress in understanding BC pathogenesis and therapeutic options, there is still a need to identify new therapeutic targets and develop more effective treatments. According to recent sequencing and profiling studies, non-coding (nc) RNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation, and similarly, the expression of many ncRNAs is altered in breast cancer cell lines and tissues. The ability of single ncRNAs to regulate the expression of multiple downstream gene targets and related pathways provides a theoretical basis for studying them for cancer therapeutic drug development and targeted delivery. Therefore, it is far-reaching to explore the role of ncRNAs in tumor development and their potential as therapeutic targets. Here, our review outlines the potential of two major ncRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) as diagnostic and prognostic biomarkers as well as targets for new therapeutic strategies in breast cancer.

Gastric cancer (GC) is considered a global health crisis due to the scarcity of early diagnostic methods. Numerous studies have substantiated the involvement of histone acetylation imbalance in the progression of diverse tumor types. The potential roles of long non-coding RNA (lncRNA) in improving prognostic, predictive as well as therapeutic approaches in cancers have made it a major hotspot in recent years. Nevertheless, existent studies have never concerned the prognostic and clinical value of histone acetylation-related lncRNAs (HARlncs) in GC. Based on the aforementioned rationale, we developed a prognostic model incorporating four HARlncs—AC114730.1, AL445250.1, LINC01778, and AL163953.1—which demonstrated potential as an independent predictor of prognosis. Subsequently, GC patients were stratified into high-risk and low-risk groups. The low-risk group exhibited significantly higher overall survival (OS) compared to the high-risk group. Based on the analyses of the tumor microenvironment (TME) and immune responses, significant differences were observed between the two risk groups in terms of immune cell infiltration, immune checkpoint (ICP) expression, and other TME alterations. Furthermore, the sensitivity of GC patients to some chemotherapeutic drugs and the discrepant biological behaviors of three tumor clusters were studied in this model. In summary, we developed an effective HARlncs model with the objective of offering novel prognostic prediction methods and identifying potential therapeutic targets for GC patients.

Non-coding RNAs have emerged as important regulators of gene expression and contributors to many diseases. LncRNA Morrbid, a long non-coding RNA, has been widely studied in recent years. Current literature reports that lncRNA Morrbid is involved in various diseases such as tumors, cardiovascular diseases, inflammatory diseases and metabolic disorder. However, controversial conclusions exist in current studies. As a potential therapeutic target, it is necessary to comprehensively review the current evidence. In this work, we carefully review the literature on Morrbid and discuss each of the hot topics related to lncRNA Morrbid.

RNA N6-methyladenosine (m6A) methylation is the most abundant and conserved RNA modification in eukaryotes. It participates in the regulation of RNA metabolism and various pathophysiological processes. Non-coding RNAs (ncRNAs) are defined as small or long transcripts which do not encode proteins and display numerous biological regulatory functions. Similar to mRNAs, m6A deposition is observed in ncRNAs. Studying RNA m6A modifications on ncRNAs is of great importance specifically to deepen our understanding of their biological roles and clinical implications. In this review, we summarized the recent research findings regarding the mutual regulation between RNA m6A modification and ncRNAs (with a specific focus on microRNAs, long non-coding RNAs, and circular RNAs) and their functions. We also discussed the challenges of m6A-containing ncRNAs and RNA m6A as therapeutic targets in human diseases and their future perspective in translational roles.

Abstract It was aimed to evaluate long non-coding RNAs (lncRNAs) in terms of diagnosis and prognosis in colorectal cancer (CRC) cases with peritoneal metastasis who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Paraffinized 32 CRC tissue and 32 adjacent normal colon tissue of 32 cases, and paraffinized metastatic 10 peritoneal tumor tissue and 10 adjacent normal peritoneal tissues of 10 cases were included in. Expression levels of lncRNAs GAS5, MALAT1, CCAT2, HOTAIR and H19 were measured by qRT-PCR, clinicopathological and demographic characteristics of the patients were also recorded. 11 (34%) patients were female and 21 (66%) were male. The mean age was 54.59±11.97 (24-73 years). Expression levels of GAS5 decreased significantly in colon tumor tissues compared to normal colon tissues (p

Myocardial infarction (MI) stands at top global causes of death in developed countries, owing mostly to atherosclerotic plaque growth and endothelial injury-induced reduction in coronary blood flow. While early reperfusion techniques have improved outcomes, long-term treatment continues to be difficult. The function of lncRNAs extends to regulating gene expression in various conditions, both physiological and pathological, such as cardiovascular diseases. The objective of this research is to extensively evaluate the significance of the lncRNA called Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in the development and management of MI. According to research, MALAT1 is implicated in processes such as autophagy, apoptosis, cell proliferation, and inflammation in the cardiovascular system. This investigation examines recent research examining the effects of MALAT1 on heart function and its potential as a mean of diagnosis and treatment for post- MI complications and ischemic reperfusion injury.

Abstract Background Medulloblastomas (MBs) are one of the most common malignant brain tumor types in children. MB prognosis, despite improvement in recent years, still depends on clinical and biological risk factors. Metastasis is the leading cause of MB-related deaths, which highlights an unmet need for risk stratification and targeted therapy to improve clinical outcomes. Among the four molecular subgroups, sonic-hedgehog (SHH)-MB harbors clinical and genetic heterogeneity with a subset of high-risk cases. Recently, long non-coding (lnc)RNAs were implied to contribute to cancer malignant progression, but their role in MB remains unclear. This study aimed to identify pro-malignant lncRNAs that have prognostic and therapeutic significance in SHH-MB. Methods The Daoy SHH-MB cell line was engineered for ectopic expression of MYCN, a genetic signature of SHH-MB. MYCN-associated lncRNA genes were identified using RNA-sequencing data and were validated in SHH-MB cell lines, MB tissue samples, and patient cohort datasets. SHH-MB cells with genetic manipulation of the candidate lncRNA were evaluated for metastatic phenotypes in vitro, including cell migration, invasion, sphere formation, and expressions of stemness markers. An orthotopic xenograft mouse model was used to evaluate metastasis occurrence and survival. Finally, bioinformatic screening and in vitro assays were performed to explore downstream mechanisms. Results Elevated lncRNA LOXL1-AS1 expression was identified in MYCN-expressing Daoy cells and MYCN-amplified SHH-MB tumors, and was significantly associated with lower survival in SHH-MB patients. Functionally, LOXL1-AS1 promoted SHH-MB cell migration and cancer stemness in vitro. In mice, MYCN-expressing Daoy cells exhibited a high metastatic rate and adverse effects on survival, both of which were suppressed under LOLX1-AS1 perturbation. Integrative bioinformatic analyses revealed associations of LOXL1-AS1 with processes of cancer stemness, cell differentiation, and the epithelial-mesenchymal transition. LOXL1-AS1 positively regulated the expression of transforming growth factor (TGF)-β2. Knockdown of TGF-β2 in SHH-MB cells significantly abrogated their LOXL1-AS1-mediated prometastatic functions. Conclusions This study proved the functional significance of LOXL1-AS1 in SHH-MB metastasis by its promotion of TGF-β2-mediated cancer stem-like phenotypes, providing both prognostic and therapeutic potentials for targeting SHH-MB metastasis.

Abstract There has been increasing interest in the role of epigenetic modification in cancers recently. Among the various modifications, sialylation has emerged as a dominant subtype implicated in tumor progression, metastasis, immune evasion, and chemoresistance. The prognostic significance of sialylation-related molecules has been demonstrated in colorectal cancer. However, the potential roles and regulatory mechanisms of sialylation in lung adenocarcinoma (LUAD) have not been thoroughly investigated. Through Pearson correlation, univariate Cox hazards proportional regression, and random survival forest model analyses, we identified several prognostic long non-coding RNAs (lncRNAs) associated with aberrant sialylation and tumor progression, including LINC00857, LINC00968, LINC00663, and ITGA9-AS1. Based on the signatures of four lncRNAs, we classified patients into two clusters with different landscapes using a non-negative matrix factorization approach. Collectively, patients in Cluster 1 (C1) exhibited worse prognoses than those in Cluster 2 (C2), as well as heavier tumor mutation burden. Functional enrichment analysis showed the enrichment of several pro-tumor pathways in C1, differing from the upregulated Longevity and programmed cell death pathways in C2. Moreover, we profiled immune infiltration levels of important immune cell lineages in two subgroups using MCPcounter scores and single sample gene set enrichment analysis scores, revealing a relatively immunosuppressive microenvironment in C1. Risk analysis indicated that LINC00857 may serve as a pro-tumor regulator, while the other three lncRNAs may be protective contributors. Consistently, we observed upregulated LINC00857 in C1, whereas increased expressive levels of LINC00968, LINC00663, and ITGA9-AS1 were observed in C2. Finally, drug sensitivity analysis suggested that patients in the two groups may benefit from different therapeutic strategies, contributing to precise treatment in LUAD. By integrating multi-omics data, we identified four core sialylation-related lncRNAs and successfully established a prognostic model to distinguish patients with different characterizations. These findings may provide some insights into the underlying mechanism of sialylation, and offer a new stratification way as well as clinical guidance in LUAD.

Abstract Background Long non-coding RNAs (LncRNAs) regulating the immune microenvironment of cancer is a hot spot. But little is known about the influence of the immune-related lncRNA (IRlncRs) on the chemotherapeutic responses and prognosis of cervical cancer (CC) patients. The purpose of the study was to identify an immune-related lncRNAs (IRlncRs)-based model for the prospective prediction of clinical outcomes in CC patients. Methods CC patients’ relevant data was acquired from The Cancer Genome Atlas (TCGA). Correlation analysis and Cox regression analyses were applied. A risk score formula was formulated. Prognostic factors were combined into a nomogram, while sensitivity for chemotherapy drugs was analyzed using the OncoPredict algorithm. Results Eight optimal IRlncRs(ATP2A1-AS1, LINC01943, AL158166.1, LINC00963, AC009065.8, LIPE-AS1, AC105277.1, AC098613.1.) were incorporated in the IRlncRs model. The overall survival (OS) of the high-risk group of the model was inferior to those in the low-risk group. Further analysis demonstrated this eight-IRlncRs model as a useful prognostic marker. The Nomogram had a concordance index of survival prediction of 0.763(95% CI 0.746–0.780) and more robust predictive accuracy. Furthermore, patients in the low-risk group were found to be more sensitive to chemotherapy, including Paclitaxel, Rapamycin, Epirubicin, Vincristine, Docetaxel and Vinorelbine. Conclusions An eight-IRlncRs-based prediction model was identified that has the potential to be an important tool to predict chemotherapeutic responses and prognosis for CC patients.

Objective To explore the correlation between the expression of long non-coding RNA(lncRNA) UCA1 and radiotherapy sensitivity in patients with esophageal squamous cell carcinoma. Methods A total of 80 patients with esophageal squamous cell carcinoma admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from February 2020 to February 2022 were selected as the esophageal cancer group, and 50 subjects who underwent health examinations in our hospital during the same period were selected as the control group.Real time fluorescence quantitative PCR was used to detect the plasma lncRNA UCA1 expression levels of all subjects and compare them.The relationship between lncRNA UCA1 levels and clinical pathological indicators in esophageal cancer patients, as well as their relationship with radiation sensitivity, was analyzed. Results The plasma lncRNA UCA1 levels in the esophageal cancer group were higher than those in the control group, and the difference was statistically significant(P0.05);The plasma lncRNA UCA1 levels in patients with TNM stage Ⅲ+Ⅳ esophageal squamous cell carcinoma were higher than those in patients with stage Ⅰ+Ⅱ, and the difference was statistically significant(P2.31) showed a significant decrease in radiotherapy sensitivity(P

There is increasing evidence that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of malignant tumors, particularly pancreatic cancer. In this study, the influence of the lncRNA TINCR on the behavior of human pancreatic cancer cells was investigated with the aim of deciphering its role in growth, migration, and invasion. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate TINCR expression in pancreatic cancer cells. Ectopic expression of TINCR in PANC-1 cells was induced to evaluate the effects on cell viability and apoptosis, examining the apoptotic genes Bax and Bcl-2. Migration and invasion assays were used to measure the impact of TINCR on these cellular processes. In vivo studies using a xenograft mouse model examined the effects of TINCR on tumor growth, epithelial-to-mesenchymal transition (EMT) markers, and the Wnt/β-catenin signaling pathway. PANC-1 cells showed strikingly low TINCR expression compared to other pancreatic cancer cell lines. Ectopic TINCR expression reduced the viability of PANC-1 cells primarily by inducing apoptosis, as evidenced by increased Bax and decreased Bcl-2 expression. Overexpression of TINCR significantly increased the percentage of apoptotic cells. It also decreased the migration and invasion ability of PANC-1 cells, as demonstrated in wound healing and transwell assays. In addition, overexpression of TINCR-suppressed proteins is associated with the Wnt/β-catenin signaling pathway in PANC-1 cells. In the xenograft mouse model, overexpression of TINCR inhibited tumor growth, EMT markers, and proteins associated with the Wnt/β-catenin pathway. This study sheds light on the tumour-suppressive role of TINCR in PANC-1 cells and suggests its potential as a therapeutic target. These results shed light on the molecular mechanisms underlying the impact of TINCR on pancreatic cancer and offer promising opportunities for innovative therapeutic strategies to improve outcomes in this serious malignancy.

Abstract Background Diabetic cardiomyopathy (DCM) is becoming a very well-known clinical entity and leads to increased heart failure in diabetic patients. Long non-coding RNAs (LncRNAs) play an important role in the pathogenesis of DCM. In the present study, the expression profiles of lncRNAs and mRNAs were illuminated in myocardium from DCM mice, with purpose of exploring probable pathological processes of DCM involved by differentially expressed genes in order to provide a new direction for the future researches of DCM. Results The results showed that a total of 93 differentially expressed lncRNA transcripts and 881 mRNA transcripts were aberrantly expressed in db/db mice compared with the controls. The top 6 differentially expressed lncRNAs like up-regulated Hmga1b, Gm8909, Gm50252 and down-regulated Msantd4, 4933413J09Rik, Gm41414 have not yet been reported in DCM. The lncRNAs-mRNAs co-expression network analysis showed that LncRNA 2610507I01Rik, 2310015A16Rik, Gm10503, A930015D03Rik and Gm48483 were the most relevant to differentially expressed mRNAs. Conclusion Our results showed that db/db DCM mice exist differentially expressed lncRNAs and mRNAs in hearts. These differentially expressed lncRNAs may be involved in the pathological process of cardiomyocyte apoptosis and fibrosis in DCM.

Abstract Long intergenic non-protein coding RNA, P53 induced transcript (LINC-PINT) exhibits different expression patterns in the majority of tumors, yet its relationship with cancer prognosis remains a subject of debate. This study aims to comprehensively investigate the prognostic significance of LINC-PINT in diverse human cancer. A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science databases to identify pertinent studies exploring the correlation between LINC-PINT expression and cancer patients. Moreover, bioinformatics analysis and in vitro validation were used to validate the results of the meta-analysis and to investigate the potential oncogenic mechanism of LINC-PINT. The meta-analysis encompassed 8 studies, involving 911 patients. The pooled analysis demonstrated a significant association between upregulation of LINC-PINT expression and better survival (P = 0.002) during the cancers. Meanwhile, its downregulation was correlated with advanced tumor staging (P = 0.04) and tumor differentiation (P = 0.03). Additionally, bioinformatics analysis showed that LINC-PINT expression was observed to be linked with Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) in tumors, the results of bioinformatics were verified by qRT-PCR. And functional enrichment analysis hinted at its involvement in tumorigenesis and tumor progression. Dysregulated LICN-PINT expression is associated with the clinical prognostic and pathological features of various cancers, exhibiting substantial potential as a novel prognostic biomarker.