A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation. This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus, one of the most common neurological conditions worldwide. In this review, we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition. Then, we outline the definition, classification, and biological role of non-coding RNAs. Subsequently, we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail. Specifically, we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus, including glymphatic pathways, neuroinflammatory processes, and neurological dysplasia, on the basis of the existing evidence. Lastly, we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.

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.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, associated with high morbidity and mortality worldwide. Despite advancements in diagnostic methods and systemic treatments, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), the development of drug resistance remains a significant challenge in HCC management. Traditional treatments such as surgical resection and transarterial chemoembolization offer limited efficacy, especially in advanced stages. Although novel therapies like lenvatinib, sorafenib, regorafenib, and ICIs have shown promise, their effectiveness is often hindered by primary and acquired resistance, leading to poor long-term survival outcomes. This review focuses on the molecular mechanisms underlying resistance to targeted therapies and immunotherapies in HCC. Key factors contributing to resistance include alterations in the tumor microenvironment (TME), immune evasion, hypoxia, changes in cellular metabolism, and genetic mutations. Additionally, molecular players such as ferroptosis, autophagy, apoptosis, endoplasmic reticulum stress, ABC transporters, and non-coding RNAs(ncRNAs) are discussed as contributors to drug resistance. Understanding these mechanisms is critical for the development of novel therapeutic strategies aimed at overcoming resistance, improving patient outcomes, and ultimately enhancing survival rates in HCC patients.

Pulmonary artery endothelial cell (PAEC) dysfunction is a pathological hallmark of pulmonary hypertension (PH). Yet, the roles of long noncoding RNAs (lncRNAs) driven by super-enhancers (SEs) in PAECs are not well understood. In this study, we focused on the PAEC-specific SE-associated lncRNA HCG20 (HLA complex group 20) and to elucidate its role and underlying mechanisms in the progression of PH.

ChIP-qPCR, chromosome conformation capture followed by PCR, CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and dual-luciferase reporter assays were used to identify dysregulated SE-associated lncRNAs in PAECs and to investigate the pathological role of HCG20. The role of HCG20 in pathological processes was validated in rodent models of PH induced by SU5416/hypoxia, monocrotaline, or hypoxia alone, through adeno-associated virus-mediated endothelial-specific HCG20 overexpression or knockdown of HCG20. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and RNA sequencing were used to elucidate the underlying mechanisms of HCG20-mediated PAEC dysfunction.

We identified the SE-associated lncRNA HCG20 from histone H3 lysine-27 acetylation (H3K27ac) and histone H3 lysine-4 monomethylation (H3K4me1) ChIP-seq data derived from PAECs of patients with PH. A significant upregulation of HCG20 was found in hypoxia-induced human PAECs, lung tissues, and the plasma of patients with PH. Antisense oligonucleotide and CRISPR/Cas9, which, respectively, target HCG20 and its SE, alleviate hypoxia-induced pyroptosis and subsequent endothelial-to-mesenchymal transition. Human pulmonary artery smooth muscle cells internalize human PAEC-derived exosomes containing HCG20, inducing their excessive proliferation. Targeted delivery of HCG20 into the pulmonary vascular endothelium induced pulmonary vasculature remodeling and increased pulmonary artery systolic blood pressure in rodents. Mechanistically, HCG20 directly bound and stabilized the U2AF2 (U2 small nuclear RNA auxiliary factor 2) protein, thereby facilitating its impact on the alternative splicing of EIF2AK2 (eukaryotic translation initiation factor 2 alpha kinase 2). Furthermore, we identified a novel mouse ortholog gene, 4833427F10Rik (named Hcg20), of HCG20 for the first time. Our study demonstrated that specific interference with Hcg20 in the pulmonary vascular intima has been shown to ameliorate hypoxia-induced PH.

Collectively, our data suggest that HCG20, driven by SE, contributes to PAEC dysfunction through U2AF2-mediated alternative splicing of EIF2AK2. Our work underscores the potential of using HCG20 as a novel biomarker and a promising target for the treatment of PH.

Dysregulated expression of long non-coding RNAs (lncRNAs) in cancer contributes to various hallmarks of the disease, presenting novel opportunities for diagnosis and therapy. G-quadruplexes (G4s) within lncRNAs have gained attention recently; however, their systematic evaluation in cancer biology is yet to be performed. In this work, we have formulated a comprehensive dataset integrating experimentally-validated associations between lncRNAs and cancer, and detailed predictions of their G4-forming potential. The dataset categorizes predicted G4-motifs into anticipated G4 types (2 G, 3 G, and 4 G) and provides information about the subcellular localization of the corresponding lncRNAs. It describes lncRNA-RNA and lncRNA-protein interactions, together with the RNA G4-binding capabilities of these proteins. The dataset facilitates the investigation of G4-mediated lncRNA functions in diverse human cancers and provides distinctive leads about G4-mediated lncRNA-protein interactions.

Thyroid cancer (TC) represents the most common endocrine malignancy; however, the intricacies of its carcinogenesis pose significant challenges to therapeutic interventions. A comprehensive understanding of the molecular mechanisms that drive TC progression is crucial for the development of effective treatment strategies, especially considering the increasingly recognized role of non-coding RNAs (ncRNAs) in oncogenesis. Notwithstanding recent advancements, the regulatory functions of long non-coding RNAs (lncRNAs) and their interactions with microRNAs (miRNAs) in the context of TC are not yet fully elucidated. This review aims to address this knowledge deficiency by investigating the dual roles of lncRNAs in the pathogenesis of TC, specifically their regulation of programmed cell death (PCD) pathways. Current literature indicates that disrupted competitive endogenous RNA (ceRNA) networks are involved in drug resistance, epithelial-mesenchymal transition (EMT), as well as tumor proliferation, angiogenesis, invasion, and metastasis in TC. The basis of cancer therapy-induced tumor cell elimination is programmed cell death (PCD), which includes well-studied processes such as apoptosis, autophagy, and ferroptosis as well as novel pathways, such as cuproptosis, immunogenic cell death (ICD), and PANoptosis. Recent research has shown the critical function of long non-coding RNAs (lncRNAs) in modifying these several PCD pathways, impacting TC growth and therapy response. This review synthesizes evidence on how lncRNAs regulate PCD to influence TC progression and therapeutic outcomes. Additionally, we examine the clinical relevance of lncRNAs in TC, highlighting their potential as biomarkers for diagnosis and prognosis, therapeutic targets, and contributors to drug resistance, while emphasizing recent advancements in this field.

To identify novel genetic loci for children refractive error, we performed a meta-analysis of two genome-wide association studies (GWASs) of spherical equivalent (SE) in 1,237 children from the population-based Hong Kong Children Eye Study (HKCES) and the Low Concentration Atropine for Myopia Progression (LAMP) study. Replication was conducted in 4,093 Chinese children and 1,814 Chinese adults. Four lead-SNPs (MIR4275 rs292034, TENM3 rs17074027, LOC101928911 rs6925312 and FAM135B rs4609227) showed genome-wide significant association (P ≤ 5.0 × 10-8) with SE. TENM3 had been associated with myopia in adults before, whilst the other three loci, MIR4275, LOC101928911 and FAM135B, were novel. Significant interaction between genetic risk scores (GRS) and near work on SE was also detected (βinteraction = 0.14, Pinteraction = 0.0003). This study identified novel genetic loci for children refractive error and suggested myopia intervention can be individualized based on the genetic risk of children.

This study aims to explore the role of Disulfidptosis-Related long Non-Coding RNAs (DRlncRNAs) in the prognosis and immune infiltration of Head and Neck Squamous Cell Carcinoma (HNSCC).

Using bioinformatics approaches, this study investigates the prognostic significance of DRlncRNAs in HNSCC patients and their potential association with the immune microenvironment. RNA sequencing data and clinical information for HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. DRlncRNAs were identified through Pearson correlation analysis, and a prognostic model consisting of six DRlncRNAs was constructed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, along with univariate and multivariate Cox analyses.

The predictive performance of the model was assessed using Receiver Operating Characteristic (ROC) curves and Principal Component Analysis (PCA), and further validated using calibration curves, a nomogram, and univariate/multivariate Cox analyses. In addition to functional enrichment analysis, the associations between the model and Tumor Mutation Burden (TMB), immune cell infiltration, and drug sensitivity were also examined.

We developed a novel predictive model composed of six DRlncRNAs to predict the prognosis of HNSCC patients and proposed potential clinical therapeutic targets from the perspective of disulfidptosis.

Level 5.

HIV-1 infection in microglia induces HIV-associated neurocognitive disorder (HAND). Recent evidence suggests that microglia can be infected with HIV-1 in the active, persistent, or latent replication stages. The molecular mechanisms governing these stages of infection are still the subject of continuous study. In this study, we analyzed the relationship between HIV-1 infection and two lncRNAs, NEAT1 and ZBTB11-AS1, on different days post-infection. We found that on days 1 and 4 post-infection, HIV-1 was actively replicating; meanwhile, by day 21, HIV-1 had entered a persistent stage. We also noted that the expression levels of NEAT1 and ZBTB11-AS1 varied during these different stages of HIV-1 infection in microglia, as did their subcellular localization. We performed an interaction network analysis and identified DDX3X and ZC3HAV1 as hypothetically related to NEAT1 and ZBTB11-AS1 in the C20 human microglial cell line. Additionally, we determined that IL-6, a cytokine regulated by DDX3X and ZC3HAV1, exhibits changes in protein expression levels during both active and persistent HIV-1 infection.

Lung cancer is the most prevalent malignant tumor worldwide and remains the leading cause of cancer-related mortality. Despite advances in treatment development, lung cancer patients often face poor quality of life and low survival rates. Increasing evidence highlights the significant roles of autophagy and non-coding RNAs (ncRNAs) in the initiation, progression, and therapeutic response of lung cancer. Autophagy and ncRNAs can function as both tumor-promoting and tumor-suppressing factors in lung cancer. Therefore, investigating the roles of autophagy and ncRNAs in lung cancer provides valuable insights into its pathophysiology. At the same time, non-coding RNA also plays an important role in regulating autophagy. This study reveals that autophagy affects the occurrence and development of lung cancer through multiple pathways. Then, we also studied that in lung cancer, ncRNAs (e.g., lncRNAs, miRNAs, circRNAs and piRNAs) can regulate autophagy to promote or inhibit tumorigenesis, metastasis and drug resistance in lung cancer. Finally, the problems and solutions of autophagy and ncRNAs in the treatment of lung cancer were explored. These findings suggest that autophagy and ncRNAs can be potential targets for the treatment of lung cancer.

The objective of this study was to assess the potential of TCF7L2, CCAT2, and PVT1 LncRNAs, c-Myc, and miR-33 as biomarkers for early diagnosis and differentiation of oral squamous cell carcinoma (OSCC) and premalignant lesions.

Bioinformatics tools, including COSMIC, GeneMANIA, PathVisio, KEGG Pathway Database, IntOGen, and WikiPathways, were used to investigate the signaling pathways of cancer-associated genes. The limma package was utilized for statistical analysis to identify Differentially Expressed Genes (DEGs) between OSCC tumor and normal samples. The regulatory microRNAs were analyzed using miRDB, miRWalk, and TargetScan. The type of cancer for analysis was selected using IntOGen. The expression levels of LncRNAs, miR-33, and c-Myc were measured by polymerase chain reaction (PCR) in 28 OLP and 30 OSCC tissue samples, compared to 30 healthy and 30 OSCC-adjacent tissue specimens as control groups. Data were analyzed using the Mann-Whitney test, receiver operating characteristic (ROC) curve, and multiple linear regression.

The expression of c-Myc (3.53 ± 2.78 vs 0.93 ± 0.50), PVT1 (10.94 ± 8.49 vs 0.91 ± 0.48), CCAT2 (11.77 ± 10.00 vs 0.92 ± 0.95), and TCF7L2 (6.48 ± 4.30 vs 1.27 ± 0.96) was significantly higher in OSCC samples compared to OLP (P < 0.001). Conversely, miR-33 expression was significantly lower in OSCC samples (0.24 ± 0.25 vs 4.90 ± 3.90). There was a significant correlation between c-Myc, CCAT2, PVT1, and miR-33 expression and clinicopathological characteristics of OSCC specimens. In OSCC samples, c-Myc, PVT1, CCAT2, and TCF7L2 showed a significant positive correlation with each other, while miR-33 expression was negatively correlated with the overexpression of other genes. The area under the curve (AUC) for c-Myc, PVT-1, CCAT2, miR-33, and TCF7L2 were 0.917, 1.000, 0.979, 0.006, and 0.929, respectively.

Our findings suggest that c-Myc and LncRNAs (TCF7L2, PVT1, and CCAT2) are upregulated and miR-33 is downregulated in OSCC compared to OLP samples. These genes may serve as potential genetic biomarkers for diagnosis and prediction of clinicopathological features of OSCC.

A significant role in many cancers is played by cuproptosis, a new term for the copper-dependent regulatory cell death pattern. However, as a new research hotspot, the cuproptosis-related lncRNAs (CRLs) associated with regulation in oral squamous cell carcinoma (OSCC) patients are currently not well understood.

Long noncoding RNA (lncRNA) data were downloaded from the Cancer Genome Atlas database (TCGA). The 'LIMMA' package in R software was used to screen for differential expression of CRLs. LASSO regression and COX regression models were used to construct prognostic signature based on 4 prognostic CRLs. Finally, the relationship of risk characteristics with immune correlation analysis, somatic mutations, PCA, biological molecular pathways and drug sensitivity was investigated.

A cuproptosis-related lncRNAs prognostic signature was developed by us. Based on the risk scores, the OSCC samples were split into high- and low-risk groups using this signature. The two risk groups differed significantly in immune functions, drug sensitivity, and overall survival. The risk model showed better prognostic predictive power compared to the traditional clinicopathological signature. By qPCR trial, we also verified the expression of STARD4-AS1 in OSCC cell lines and tissues was in line with our results from this experimental screen. Through cell experiments, we have confirmed that knocking down STARD4-AS1 promotes the proliferation and migration ability of OSCC cells.

The CRLs signature contributes to new understandings of the treatment of OSCC and is a rubost biomarker for predicting the prognosis of patients with OSCC.

Serine hydroxymethyltransferase 2 (SHMT2) is a crucial mitochondrial enzyme in 1-carbon (1C) metabolism. It catalyzes the conversion of serine to glycine, generating 1C units essential for purine and pyrimidine synthesis, thereby supporting DNA replication and repair. Abnormally high expression is associated with malignant progression and treatment tolerance in various cancers. This review systematically summarizes the functions of SHMT2 in different types of cancer, underscoring on its roles in metabolism, immune microenvironment, and key signaling pathways (PI3K/AKT/mTOR, JAK-STAT, etc.) and outlines its epigenetic regulation and posttranslational modification mechanisms. Compared with the existing research, we focused on the latest regulatory mechanisms of SHMT2 and its potential in cancer treatment, such as the development and application of small-molecule inhibitors (SHIN2 and AGF347).

Coronary artery disease (CAD) is a major cardiovascular disease that affects global population health. Several studies have indicated the association between high expression level of a non-coding RNA, lncMALAT1 and an increased risk of CAD. In this study, we conducted a protocol of systematic review aims to evaluate the role and mechanism of lncMALAT1 that may contributed to CAD based on animal and in vitro studies. The roles of lncMALAT1 will be elucidated focusing on activating upstream signalling Klotho/FGF23 or regulate the downstream Wnt/β-catenin or extracellular signal-regulated kinase/mitogen-activated protein kinase(ERK/MAPK) and any other pathways with the vascular changes in term of proliferation, migration, lumen formation and apoptosis.

A systematic review protocol with a reproducible strategy according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines and Population, Intervention, Comparison Outcome and Study (PICOS) framework were proposed to evaluate the existing literature on the roles and mechanisms of the lncMALAT1. A PRISMA-compliant electrical systematic research was performed in the databases including PubMed, Web of Science and Scopus for English publication from their inceptions until January 2024. Data for collection will include primary CAD animal models and any cardiomyocyte cell line with primary hypoxia model. The article title, authors, type of models, signaling pathways and biological changes (proliferation, migration, lumen formation and apoptosis) will be recorded.

This will provide a new approach in understanding molecular interactions on CAD for new perspective and target treatment for CAD patients in future, especially that intolerance of invasive coronary therapy.

Registered in PROSPERO on 10 April, 2024. (CRD42024504245) (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024504245).

Lung squamous cell carcinoma (LUSC), a major subtype of non-small cell lung cancer, remains challenging to treat due to poor prognosis and limited therapeutic options. This study investigates the prognostic and therapeutic implications of copper-induced cell death-related long non-coding RNAs (lncRNAs) in LUSC using data from The Cancer Genome Atlas. Five lncRNAs (AC010328.1, LINC01740, AL358613.2, MIR3945HG, AC002467.1) were identified as independent prognostic markers and incorporated into a risk score model to stratify patients into high- and low-risk groups. Survival analyses revealed significant differences in overall survival, with the high-risk group exhibiting higher immune evasion potential and poorer response to immunotherapy. Functional enrichment analyses highlighted the involvement of these lncRNAs in drug metabolism and tumor biology. Furthermore, tumor mutation burden analysis and immune dysfunction evaluation confirmed the clinical relevance of the model, identifying high-risk patients as more sensitive to targeted drugs such as Quizartinib and Dasatinib. A Nomogram integrating lncRNA risk scores and clinical factors demonstrated robust predictive accuracy for 1-, 3-, and 5-year survival outcomes. This study provides novel biomarkers and actionable insights for improving prognostic assessment and personalizing immunotherapy strategies for LUSC patients.

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.

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.

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.

Long non-coding RNAs (lncRNAs) have been shown to be integral in a variety of biological processes and significantly influence the progression of several human diseases. Their involvement in disease mechanisms makes them crucial targets for research in disease biomarker identification. Understanding the intricate relationships between lncRNAs and diseases can offer valuable insights for advancing diagnostic, prognostic and therapeutic strategies. In light of this, we propose a recommendation-system-based model utilizing matrix factorization with disease neighborhood regularization to effectively infer disease-related lncRNAs (NRMFLDA). This approach leverages the power of matrix factorization techniques while incorporating disease neighborhood regularization to enhance the accuracy and reliability of lncRNA-disease association predictions. Consequently, NRMFLDA exhibits outstanding performance, achieving AUC scores of 0.9143 and 0.8993 in both leave-one-out and five-fold cross-validation, surpassing the performance of four previous models. This demonstrates its effectiveness and robustness in accurately predicting disease-related lncRNAs. We believe that NRMFLDA will not only provide innovative approaches for uncovering lncRNA-disease associations but also contribute significantly to the identification of novel biomarkers for various diseases, thereby advancing diagnostic and therapeutic strategies.

Osteoporosis (OP) is a disease affecting bone metabolism, characterized by low bone mineral density and the deterioration of the bone microarchitecture, leading to increased bone fragility and risk of fracture. OP mainly results from alterations in the balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Currently, there are several molecular mechanisms underlying the development of OP that are not entirely clear. One such mechanism is the role of long non-coding RNAs, which are key regulators of gene expression through various mechanisms. In the last decade, it has been shown that these molecules participate in multiple biological processes and play essential roles in the pathogenesis of different diseases. In this review, we address recent advances on the relationship of long non-coding RNAs with OP, mainly over their regulatory functions during osteoclastogenesis and osteogenesis. Furthermore, we analyze their potential application as clinical or therapeutic resources focused on OP.

Non-coding RNAs play crucial roles in disease initiation and progression, making them promising biomarkers for early diagnosis and treatment monitoring. Conventional nucleic acid diagnostic methods, including polymerase chain reaction (PCR), next-generation sequencing (NGS), and enzyme-linked immunosorbent assay (ELISA), alongside emerging techniques such as single-molecule fluorescence in situ hybridization (smFISH), nanopore sequencing, and single-cell RNA sequencing (scRNA-seq), face inherent limitations in detecting regulatory non-coding RNAs. These challenges include laborious workflows, prolonged processing times, and technical complexities, hindering their broad applicability in rapid and high-throughput RNA analysis. CRISPR/Cas13a-based biosensors, integrated with various signal transduction systems-such as fluorescence, electrochemistry, colorimetry, surface-enhanced Raman spectroscopy (SERS)-show great promise for real-world diagnostic applications. This review provides a comprehensive overview of the CRISPR/Cas13a-mediated RNA detection mechanism, the development of CRISPR/Cas13a-based biosensors, and their integration with innovative signal detection methods. Additionally, we highlight the progress in portable detection devices, including lateral flow assay strips and smartphone-based platforms. Finally, the review discusses the current challenges and future prospects of CRISPR/Cas13a-based biosensors, particularly in the context of clinical diagnostics and personalized medicine.

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.

Hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular adaptation to hypoxia, drives colorectal cancer (CRC) progression by fueling angiogenesis, metastasis, and therapy resistance. Emerging evidence delineates intricate crosstalk between non-coding RNAs (ncRNAs)-including microRNAs, long non-coding RNAs, and circular RNAs-and HIF-1α, forming bidirectional regulatory networks that orchestrate CRC pathogenesis. By interacting with HIF-1α, these non-coding RNAs contribute to the orchestration of the aggressive hypoxic tumor microenvironment. Recent studies have evaluated the clinical potential of lncRNAs and miRNAs in the realms of non-invasive liquid biopsies and RNA-targeted therapies. This review offers a comprehensive synthesis of recent investigations into the mechanisms by which lncRNAs and miRNAs interact with HIF-1α to modulate CRC progression. Additionally, we further explore the clinical implications of ncRNA/HIF-1α crosstalk, emphasizing their potential as diagnostic biomarkers and therapeutic targets, while also spotlighting intriguing and promising areas of ncRNA research. Methods: In this study, our search strategy employed in databases such as PubMed, Web of Science, and EMBASE is as follows: we will specify search terms, including combinations of "non-coding RNA", "HIF-1α", and "colorectal cancer", along with a date range for the literature search (for example, from 2000 to 2025) to capture the most relevant and up-to-date research.

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.

Innovative strategies are needed to curb the global health challenge of antibiotic resistance. The World Health Organization predicts that antibiotic resistance could lead to millions of deaths annually. Pharmaceutical experience has shown that modest alterations of commonly-used broad-spectrum antibiotics readily elicit resistant strains. Thus, continued simple iterative improvements on current antibiotics are not sustainable. Traditional strategies target single sites with the goal of a broad-spectrum antibiotic. In comparison, a novel strategy targets multiple sites in single- or multidrug-resistant Gram-positive bacterial pathogens. The objective is to exploit the mechanisms by which pathogenic bacteria require genes for transcriptional regulation. Transcription regulatory factors can be manipulated and their functions disrupted to hamper bacterial viability. Some transcription factors regulate one or more steps in metabolic pathways. Transcription factors are not always proteins; some are small-molecule metabolites triggering genetic functions through riboswitches, and others are RNAs. Novel agents have been discovered with computer-simulated docking to an unusual transcription regulatory site in nascent bacterial mRNA. These compounds exhibit innovative chemistries and modes of action that inhibit bacterial growth by binding to and blocking critical Gram-positive mRNA functions. The tRNA-dependent transcription regulation of amino acid metabolism illustrates the possibilities of novel strategies to inhibit antibiotic-resistant growth and thwart the emergence of novel resistant strains.

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.

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.