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Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses, intracellular bacteria, and cancers. Through biochemical analysis of RNA:protein interactions, we uncovered a non-coding RNA circuit regulating activation and differentiation of cytotoxic T cells composed of the long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and the microRNA family miR-15/16. miR-15/16 is a widely and highly expressed tumor suppressor miRNA family important for cell proliferation and survival. miR-15/16 play important roles in T cell responses to viral infection, including the regulation of antigen-specific T cell expansion and memory. Comparative Argonaute-2 high-throughput sequencing of crosslinking immunoprecipitation (AHC) combined with gene expression profiling in normal and miR-15/16-deficient mouse T cells revealed a large network of hundreds of direct miR-15/16 target mRNAs, many with functional relevance for T cell activation, survival and memory formation. Among these targets, Malat1 contained the largest absolute magnitude miR-15/16-dependent AHC peak. This binding site was among the strongest lncRNA:miRNA interactions detected in the T cell transcriptome. We used CRISPR targeting with homology directed repair to generate mice with a 5-nucleotide mutation in the miR-15/16-binding site in Malat1. This mutation interrupted Malat1:miR-15/16 interaction, and enhanced the repression of other miR-15/16 target genes, including CD28. Interrupting Malat1 interaction with miR-15/16 decreased cytotoxic T cell activation, including the expression of interleukin 2 (IL-2) and a broader CD28-responsive gene program. Accordingly, Malat1 mutation diminished memory cell persistence in mice following LCMV Armstrong and Listeria monocytogenes infection. This study marks a significant advance in the study of long non-coding RNAs in the immune system by ascribing cell-intrinsic, sequence-specific in vivo function to Malat1. These findings have implications for T cell-mediated autoimmune diseases, antiviral and anti-tumor immunity, as well as lung adenocarcinoma and other malignancies where Malat1 is overexpressed.

IntroductionOculomotor nerve palsy (ONP) arises from primary abnormalities in the central neural pathways that control the extraocular muscles (EOMs). Long non-coding RNAs (lncRNAs) have been found to be involved in the pathogenesis of various neuroparalytic diseases. However, little is known about the role of lncRNAs in ONP.MethodsWe collected medial rectus muscle tissue from ONP and constant exotropia (CXT) patients during strabismus surgeries for RNA sequencing analysis. Differentially expressed mRNAs and lncRNAs were revealed and included in the functional enrichment analysis. Co-expression analysis was conducted between these differentially expressed mRNAs and lncRNAs, followed by target gene prediction of differentially expressed lncRNAs. In addition, lncRNA-microRNA and lncRNA-transcription factor-mRNA interaction networks were constructed to further elaborate the pathological changes in medial rectus muscle of ONP. Furthermore, RT-qPCR was applied to further validate the expression levels of important lncRNAs and mRNAs, whose clinical significance was examined by receiver operating characteristic (ROC) curve analysis.ResultsA total of 618 differentially expressed lncRNAs and 322 differentially expressed mRNAs were identified. The up-regulated mRNAs were significantly related to cholinergic synaptic transmission (such as CHRM3 and CHRND) and the components and metabolism of extracellular matrix (such as CHI3L1 and COL19A1), while the down-regulated mRNAs were significantly correlated with the composition (such as MYH7 and MYL3) and contraction force (such as MYH7 and TNNT1) of muscle fibers. Co-expression analysis and target gene prediction revealed the strong correlation between MYH7 and NR_126491.1 as well as MYOD1 and ENST00000524479. Moreover, the differential expressions of lncRNAs (XR_001739409.1, NR_024160.1 and XR_001738373.1) and mRNAs (CDKN1A, MYOG, MYOD1, MYBPH, TMEM64, STATH, and MYL3) were validated by RT-qPCR. ROC curve analysis showed that lncRNAs (XR_001739409.1, NR_024160.1, and NR_002766.2) and mRNAs (CDKN1A, MYOG, MYOD1, MYBPH, TMEM64, and STATH) might be promising biomarkers of ONP.ConclusionsThese results may shed light on the molecular biology of EOMs of ONP, as well as the possible correlation of lncRNAs and mRNAs with clinical practice.

Genomic imprinting is an epigenetic process whereby genes are monoallelically expressed in a parent-of-origin-specific manner. Imprinted genes are frequently found clustered in the genome, likely illustrating their need for both shared regulatory control and functional inter-dependence. The Dlk1-Dio3 domain is one of the largest imprinted clusters. Genes in this region are involved in development, behavior, and postnatal metabolism: failure to correctly regulate the domain leads to Kagami–Ogata or Temple syndromes in humans. The region contains many of the hallmarks of other imprinted domains, such as long non-coding RNAs and parental origin-specific CTCF binding. Recent studies have shown that the Dlk1-Dio3 domain is exquisitely regulated via a bipartite imprinting control region (ICR) which functions differently on the two parental chromosomes to establish monoallelic expression. Furthermore, the Dlk1 gene displays a selective absence of imprinting in the neurogenic niche, illustrating the need for precise dosage modulation of this domain in different tissues. Here, we discuss the following: how differential epigenetic marks laid down in the gametes cause a cascade of events that leads to imprinting in the region, how this mechanism is selectively switched off in the neurogenic niche, and why studying this imprinted region has added a layer of sophistication to how we think about the hierarchical epigenetic control of genome function.

Non-small cell lung cancer (NSCLC) is one of the most devastating cancers with a high incidence and mortality rates of all cancers. Locally advanced or metastatic NSCLC patients can benefit from platinum-based chemotherapy and targeted therapy drugs. Nevertheless, primary or acquired drug resistance will result in ineffective treatment, leading to tumor progression. The detailed mechanism underlying drug resistance to NSCLC are complicated and result from various factor. Among them, long noncoding RNAs (lncRNAs) have been found to be critically involved in NSCLC development and play a vital role in mediating therapy resistance. In this review, we attempt to systematically summarize the mechanisms underlying the lncRNA-mediated resistance to chemotherapy agents and targeted therapy drugs against lung cancer.

Salinity stress typically occurs due to excessive accumulation of water-soluble salts i.e., NaCl, which can further induce osmotic stress, ionic stress as well as oxidative stress in plants, imposing many harmful effects on the growth and development of plants. However, plants respond to salinity stress through a range of cellular mechanisms which provides enhanced tolerance against salinity stress. Genetic regulation of salinity stress response through protein coding transcripts has already been extensively studied; however, involvement of non-coding transcripts such as long noncoding RNAs has recently received significant attention as an important molecule in regulating the plant response during salinity stress. Several salinity stress responsive long non coding RNAs have also been identified and characterized in various plant species. This review is an attempt to critically discuss the role of lncRNAs during salinity stress in plants.

Endometrial cancer (EC) is the most common gynecological cancer, with rising mortality rates. Targeting non-coding RNAs (ncRNAs) to diagnose and cure endometrial cancer has shown both promise and limitations in recent studies. In comparison to normal tissues, LncRNAs are differentially expressed in ECs, and their dysregulation has been associated to tumor grade, lymph node metastasis, depth of myometrial invasion, FIGO stage and patient survival. Oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, LINP1, SRA and LSINCT5) and tumor suppressor lncRNAs (GAS5, MEG3, OIP5-AS1, FER1L4, and LINC00672) have been identified as downstream effectors or upstream modulators of important signaling pathways driving EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin, and p53 signaling pathways. Short non-coding RNAs called miRNAs also effect expression of genes at the post-transcriptional level. Multiple studies have shown that miRNAs play a critical role in the regulation of EC. We present a review of ncRNA expression patterns, prognostic significance, biological function and roles in the tumor microenvironment in EC cells in EC associated pathways. We also discuss how ncRNAs can be used as biomarkers for EC diagnosis and as potential therapeutic targets for different EC subtypes based on their ncRNA signature.

Increasing evidence has uncovered the essential roles of long noncoding RNAs (lncRNAs) in biological and pathological functions of dendritic cells (DCs) among patients with systemic lupus erythematosus (SLE). However, whether lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) could modulate DCs, especially in the inflammation of SLE, remains largely unknown. Fifteen SLE patients and fifteen age-matched healthy controls were included, and their monocyte-derived dendritic cells (moDCs) were cultured in vitro. Our research identified that the expression of NEAT1 was significantly increased in moDCs of SLE patients and positively correlated with disease activity. Interleukin 6 (IL-6) from both plasma and secreted supernatants of moDCs was also elevated in the SLE group. In addition, regulation of NEAT1 in moDCs by transfection could lead to the corresponding change in IL-6 generation. While for miR-365a-3p, a micro-RNA that can bind with the 3’ UTR region of IL6 and NEAT1, it may serve as a negative modulator since its overexpression could result in the reduction of IL-6 levels and vice versa. Additionally, the elevation in NEAT1 expression could increase the secretion of IL-6 by specifically binding to miR-365a-3p, reducing the negative modulatory effects of miR-365a-3p on the IL6 target gene, which suggested that elevated NEAT1 expression could function as the competing endogenous RNA (ceRNA). In conclusion, our findings indicate that NEAT1 can efficiently sponge miR-365a-3p to upregulate expression and secretion of IL-6 in moDCs, suggesting that the NEAT1/miR-365a-3p/IL6 axis may be involved in the development of SLE disease.

Glioma is the most common malignant intracranial tumor, accounting for 80 % of all malignant brain tumors. Growing evidence suggests that lncRNAs are involved in the growth, angiogenesis, metastasis, and therapeutic resistance in a variety of tumors, including glioma. In this study, lncBIRC3-OT (NONHSAT159592.1), which is highly expressed in glioma, was screened by RNA-seq method and verified by quantitative reverse transcription polymerase chain reaction. Subsequently, we knocked down the endogenous expression of lncBIRC3-OT in U87 and U251 cells and found that down-regulated lncBIRC3-OT inhibited cell proliferation, colony formation, migration, and invasion. Mechanically, lncBIRC3-OT could guide RELA protein to the stanniocalcin-1 (STC1) promoter, initiate STC1 transcription, and ultimately promote the progression of glioma. Together, these findings suggest that lncBIRC3-OT is an important regulator promoting glioma progression, and may be a promising therapeutic target for glioma.

Worldwide, age-related macular degeneration (AMD) is a multifactorial progressive fundus disorder that can cause vision impairment and severe central blindness in older adults. Currently, there are no approved prevention or treatment strategies for non-exudative AMD. While targeting VEGF is the main therapeutic approach to delay the degeneration process in exudative AMD, a significant number of patients show insensitivity or ineffectiveness to anti-VEGF therapy. Despite years of research, the exact mechanism underlying drusen formation and macular atrophy in AMD remains unknown. In the pathogenesis of AMD, lncRNAs play crucial roles, as discussed in this paper. This review focuses on the function of dysregulated lncRNAs and the mechanisms by which specific molecules target these lncRNAs in AMD. The analysis reveals that lncRNAs primarily regulate the progression of AMD by mediating apoptosis, epithelial-mesenchymal transition (EMT), dedifferentiation, and oxidative stress in choroidal vascular endothelial cells, retinal pigment epithelium (RPE) cells, and photoreceptors. Consequently, the regulation of apoptosis, dedifferentiation, EMT, and other processes by lncRNAs has emerged as a crucial focus in AMD research.These findings contribute to our understanding of the role of lncRNAs in AMD and their potential as valuable biomarkers. Furthermore, they highlight the need for further basic and clinical studies to explore the value of lncRNAs as biomarkers and potential therapeutic targets for AMD.

Pancreatic cancer (PC) is a highly malignant disease with a 5-year survival rate of only 10%. Families with PC are at greater risk, as are type 2 diabetes, pancreatitis, and other factors. Insufficient early detection methods make this cancer have a poor prognosis. Additionally, the molecular mechanisms underlying PC development remain unclear. Increasing evidence suggests that long non-coding RNAs (lncRNAs) contribute to PC pathology,which may control gene expression by recruiting histone modification complexes to chromatin and interacting with proteins and RNAs. In recent studies, abnormal regulation of lncRNAs has been implicated in PC proliferation, metastasis, invasion, angiogenesis, apoptosis, and chemotherapy resistance suggesting potential clinical implications. The paper reviews the progress of lncRNA research in PC about diabetes mellitus, pancreatitis, cancer metastasis, tumor microenvironment regulation, and chemoresistance. Furthermore, lncRNAs may serve as potential therapeutic targets and biomarkers for PC diagnosis and prognosis. This will help improve PC patients’ survival rate from a lncRNA perspective.

Cell–cell communication is mediated by membrane receptors and their ligands, such as the Eph/ephrin system, orchestrating cell migration during development and in diverse cancer types. Epigenetic mechanisms are key for integrating external "signals", e.g., from neighboring cells, into the transcriptome in health and disease. Previously, we reported ephrinA5 to trigger transcriptional changes of lncRNAs and protein-coding genes in cerebellar granule cells, a cell model for medulloblastoma. LncRNAs represent important adaptors for epigenetic writers through which they regulate gene expression. Here, we investigate a lncRNA-mediated targeting of DNMT1 to specific gene loci by the combined power of in silico modeling of RNA/DNA interactions and wet lab approaches, in the context of the clinically relevant use case of ephrinA5-dependent regulation of cellular motility of cerebellar granule cells. We provide evidence that Snhg15, a cancer-related lncRNA, recruits DNMT1 to the Ncam1 promoter through RNA/DNA triplex structure formation and the interaction with DNMT1. This mediates DNA methylation-dependent silencing of Ncam1, being abolished by ephrinA5 stimulation-triggered reduction of Snhg15 expression. Hence, we here propose a triple helix recognition mechanism, underlying cell motility regulation via lncRNA-targeted DNA methylation in a clinically relevant context. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of N6-methyladenosine- (m6A) and neutrophil extracellular traps- (NETs) related lncRNAs (MNlncRNAs) on the prognosis of hepatocellular carcinoma (HCC). Methods: We collected m6A and NETs-related genes from published studies. We identified the MNlncRNAs by correlation analysis. Cox regression and the least absolute selection operator (LASSO) method were used to select predictive MNlncRNAs. The expressions of predictive MNlncRNAs were detected by cell and tissue experiments. Survival, medication sensitivity, and immunological microenvironment evaluations were used to assess the model’s prognostic utility. Finally, we performed cellular experiments to further validate the model’s prognostic reliability. Results: We obtained a total of 209 MNlncRNAs. 7 MNlncRNAs comprised the prognostic model, which successfully stratifies HCC patients, with the area under the curve (AUC) ranging from 0.7 to 0.8. In vitro tests confirmed that higher risk patients had worse prognosis. Risk score, immunological microenvironment, and immune checkpoint gene expression were all significantly correlated with each other in HCC. In the group at high risk, immunotherapy could be more successful. Cellular assays confirmed that HCC cells with high risk scores have a higher proliferation and invasive capacity. Conclusion: The MNlncRNAs-related prognostic model aided in determining HCC prognosis, revealing novel therapeutic options, notably immunotherapy [ABSTRACT FROM AUTHOR]

BACKGROUND: The important role of subchondral bone adjacent to the cartilage layer in the knee osteoarthritis progression has been widely recognized and the factors interfering with subchondral bone homeostasis are gradually becoming a research hotspot. Current studies have revealed that long-stranded noncoding RNAs have highlighted certain advantages and values in regulating bone homeostasis. OBJECTIVE: To understand the working mechanism of long non-coding RNAs in the subchondral bone homeostasis, thereby providing evidence for exploring new prevention and treatment methods for knee osteoarthritis. METHODS: CNKI, WanFang, VIP, PubMed, Medline, Embase, and Web of Science databases were searched with the search terms of “Long non-coding RNA, Knee osteoarthritis, Subchondral bone, Osteoblasts, Osteoclasts, Mesenchymal stem cells, Signal pathway” in Chinese and English. Literature retrieval time was from inception to July 2022, and a total of 65 articles were included in accordance with the inclusion and exclusion criteria. RESULTS AND CONCLUSION: (1) Subchondral bone homeostasis is closely related to the proliferation, differentiation, and apoptosis of mesenchymal stem cells, osteoblasts and osteoclasts, and peripheral cytokines, and angiogenesis. (2) Long non-coding RNAs can modulate various factors affecting subchondral bone homeostasis, mainly through the Wnt/β-catenin, TGF-β/BMPs/Smad, PI3K/AKT, and SDF-1/CXCR4 signaling pathways, which thereby promote or inhibit bone formation by modulating the proliferation, differentiation and apoptosis of bone marrow mesenchymal stem cells, osteoblasts and osteoclasts. It can also modulate cytokines and inhibit angiogenesis. These findings provide a theoretical basis for balancing subchondral bone homeostasis and a potential target site for the prevention and treatment of subchondral osteosclerosis in knee osteoarthritis. (3) Long non-coding RNAs are important for modulating bone formation, bone resorption, and angiogenesis. How this type of RNAs can play a role in modulating the abnormal subchondral bone in knee osteoarthritis will be a key research focus in the future. (4) Given that it is difficult to collect samples of normal human subchondral bone, there is no report on the long non-coding RNAs in normal human subchondral bone. There is still a lack of clinical studies on the direct effects of long non-coding RNAs on subchondral bone and the mechanisms of their effects on modulating subchondral bone homeostasis are not fully understood. These remain to be studied in greater depth in the future. (5) This review can preliminarily reveal the mechanism of long non-coding RNAs on subchondral bone homeostasis and summarize the relevant potential targets, which are expected to promote long non-coding RNA as a biomarker and therapeutic target for the regulation of subchondral bone in the future, thus providing new ideas for the prevention and treatment of knee osteoarthritis. [ABSTRACT FROM AUTHOR]

BACKGROUND: As the only kind of cells found in cartilage, the role of chondrocytes in osteoarthritis has received much attention. Increasing studies have found that long non-coding RNAs can participate in the pathogenesis of osteoarthritis by affecting various basic cellular characteristics of chondrocytes. OBJECTIVE: To review the research progress in the role of long non-coding RNAs in chondrocytes of osteoarthritis, thereby finding more diagnostic and therapeutic targets for osteoarthritis. METHODS: CNKI and PubMed were searched for articles addressing long non-coding RNAs in osteoarthritis published from 2007 to 2022. The search terms were “osteoarthritis; long non-coding RNA; chondrocytes; autophagy” in Chinese and “osteoarthritis; non-coding RNAs; long non-coding RNAs; chondrocytes; chondrocytes proliferation; chondrocytes autophagy; chondrocytes inflammation; chondrocytes extracellular matrix” in English. After duplicate studies and articles with low reliability and no reference were excluded, 62 articles were included for analysis, induction, and summary. RESULTS AND CONCLUSION: (1) Long non-coding RNAs can affect the development of osteoarthritis by regulating chondrocyte proliferation, autophagy, inflammatory response, and extracellular matrix synthesis. (2) Long non-coding RNAs may become a potential biomarker for the diagnosis or treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV)-B radiation is a major environmental risk factor that is responsible for the development and progression of many skin disorders. Autophagy is the process of degradation and recycling of damaged cytoplasmic organelles, macromolecular aggregates, and long-lived proteins. Previously, we found that the autophagy inducer apigenin restored UVB-impaired autophagy and the cellular response by downregulating the expression of autophagy-related genes such as ATG5. To explore long noncoding RNAs (lncRNAs) involved in regulating these autophagy-related genes, in this study, we assessed the expression profiles of lncRNAs and mRNAs using a microarray in human epidermal keratinocytes (HEKs) treated with or without apigenin after UVB radiation. The expression levels of 80 selected autophagy-related genes and related lncRNAs were confirmed by quantitative real-time polymerase chain reaction (qRT‒PCR). The lncRNA PRDM10-DT was proposed to regulate IRGM based on the ceRNA and coexpression pattern and was demonstrated to be involved in autophagy regulation, proliferation and migration of HEKs by qRT‒PCR, Western blotting, colony formation and scratch wound assays, respectively. These findings suggest an autophagy-related lncRNA in response to UVB radiation that promotes the proliferation and migration of HEKs through inducing autophagy by competing microRNAs for IRGM. [Display omitted] • Gene expression levels of BCL2L1, IRGM and RGS19 changed in response to UVB irradiation and autophagy induction. • The gene expression level of lncRNA PRDM10-DT related to IRGM changed in response to UVB irradiation and autophagy induction. • Knockdown of PRDM10-DT inhibited autophagy, proliferation and migration of human epidermal keratinocytes. [ABSTRACT FROM AUTHOR]

Objective To investigate the changes in the expression levels of long non-coding RNA (LncRNA) opioid growth factor receptor pseudogene 1 (OGFRP1) and testicular development related gene 1 (TDRG1) in endometrial carcinoma (EC) tissues, and their relationships with phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and prognosis. Methods Ninety patients with EC were selected. The expression levels of LncRNA OGFRP1, TDRG1 and PI3K, AKT mRNA in EC tissues and paraneoplastic tissues of the patients were detected by RT-qPCR. Pearson correlation was used to analyze the correlations between LncRNA OGFRP1, TDRG1 and PI3K, AKT mRNA expression in EC tissues. Based on the mean values of LncRNA OGFRP1 and LncRNA TDRG1 expression in EC tissues, patients were classified into those with high expression of LncRNA OGFRP1 and LncRNA TDRG1 and those with low expression, and the survival curves of the patients with different expression of LncRNA OGFRP1 and LncRNA TDRG1 in EC tissues were plotted using the K-M method. The relationships between LncRNA OGFRP1 and LncRNA TDRG1 expression and patients' prognosis in EC tissues were analyzed by Log-Rank test. COX regression was used to analyze the factors affecting the prognosis of EC patients. Results LncRNA OGFRP1, LncRNA TDRG1, and PI3K and AKT mRNA expression were higher in the EC tissues than in the paraneoplastic tissues (all P<0. 05). Pearson correlation analysis showed that LncRNA OGFRP1 expression was positively correlated with PI3K mRNA and AKT mRNA expression levels in EC tissues (r=0. 584, 0. 571, respectively; all P<0. 01), and LncRNA TDRG1 expression was positively correlated with PI3K mRNA and AKT mRNA expression levels (r=0. 593, 0. 584, respectively; all P<0. 01). The 3-year overall survival rates of EC patients with high expression levels of LncRNA OGFRP1 and TDRG1 were lower than those of patients with low expression levels of LncRNA OGFRP1 and TDRG1 (all P<0. 05). Cox regression analysis showed that federation international of gynecology and obstetrics stage III, lymph node metastasis, LncRNA OGFRP1 ≥1. 19, and LncRNA TDRG1 ≥1. 35 were independent risk factors affecting the prognosis of patients with EC (all P<0. 05). Conclusion LncRNA OGFRP1 and LncRNA TDRG1 expression levels increased in EC tissues, there were correlations between the expression levels of LncRNA OGFRP1 and LncRNA TDRG1 and expression levels of molecules related to the PI3K/AKT signaling pathway, and they were independent risk factors for poor prognosis of EC patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteoarthritis is one of the most common joint diseases. With the increasing global incidence and prevalence of osteoarthritis, effective early diagnosis and treatment of osteoarthritis have become an urgent problem. OBJECTIVE: To elucidate the important biological functions of long non-coding RNAs, circular RNAs and pseudogenes and their regulatory roles as competing endogenous RNAs in osteoarthritis pathogenesis to gain a comprehensive, in-depth and new understanding of the involvement of competing endogenous RNAs in osteoarthritis progression and to provide new clues for early diagnosis and treatment of osteoarthritis. METHODS: CNKI, PubMed, VIP and WanFang databases were searched for articles published before 2022. The search terms were “osteoarthritis, competing endogenous RNA, circular RNA, long non-coding RNAs, pseudogenes” in Chinese and English. RESULTS AND CONCLUSION: Non-coding RNAs with the same microRNA response elements, including long non-coding RNAs, cyclic RNAs and pseudogenes, are involved in the construction of a regulatory network of competing endogenous RNAs centered on microRNAs. Non-coding RNAs, cyclic RNAs and pseudogenes can act as competing endogenous RNAs to adsorb microRNAs through “sponge” so as to regulate gene expression. Long non-coding RNAs, cyclic RNAs and pseudogenes can act as competing endogenous RNAs to regulate the proliferation, apoptosis and autophagy of osteoarthritic chondrocytes, the synthesis and degradation of extracellular matrix and the occurrence of inflammatory events. The practical application of the regulatory network of competing endogenous RNA to the clinical setting still faces many challenges and problems. The research on competing endogenous RNA as diagnostic markers or therapeutic targets for osteoarthritis is still at an early stage, and the current research on competing endogenous RNA regulatory network is still focused on the identification and validation of individual competing endogenous RNAs, and this regulatory network needs to be further supplemented and improved. However, with the development of advanced technologies, competing endogenous RNAs are expected to become early diagnostic markers and therapeutic targets for osteoarthritis diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the change of disease treatment mode, people have realized the importance of traditional Chinese medicine in the treatment of steroidinduced necrosis of the femoral head (SANFH). Therefore, bioinformatics is used to analyze the pathogenesis of SANFH at the molecular level, build a disease risk model, and predict the potential therapeutic effects of traditional Chinese medicine, so as to provide a theoretical basis for the treatment of SANFH by traditional Chinese medicine in the future. OBJECTIVE: To mine the competing endogenous RNA regulatory network of SANFH based on bioinformatics, analyze its molecular regulatory mechanism in SANFH, predict relevant disease targets, build disease risk models, and predict Chinese herbal medicines with potential therapeutic effects. METHODS: The GEO database was searched to download the SANFH matrix file GSE123568 and gene annotation file GPL15207. The differentially expressed long non-coding RNAs and mRNAs were obtained by software analysis such as R language, and the miRNA-mRNAs associated with the differentially expressed long non-coding RNAs were predicted through the public database. Then, predicted and differentially expressed mRNAs were intersected and integrated to obtain the competing endogenous RNA network. STRING database and Cytoscape software were used to screen key genes and R language was used to analyze the functions and related pathways of key genes and mine the key competing endogenous RNA network. Finally, the risk model of SANFH was constructed according to the key genes and the prediction of traditional Chinese medicine was carried out. RESULTS AND CONCLUSION: Compared with healthy controls, a total of 7 long non-coding RNAs and 1763 mRNAs were differentially expressed in SANFH patients. Six key genes including STAT3, KAT2B, AGO4, JAK2, JAK1, and PTGS2 were identified. The enriched functions of key genes include biological processes such as response to peptide hormones, interleukin-6-mediated signaling pathways, and cell responses to interleukin-6, and are involved in signaling pathways such as JAK-STAT, adipocytokines, and prolactin. Four miRNAs (miR- 135a-5p, miR-137, miR-17-5p, miR-20b-5p) and two long non-coding RNAs (SNHG11, C20orf197) may play a key role in the occurrence and development of SANFH. KAT2B is most likely to be a risk factor for SANFH. Turmeric, Epimedium, and Astragalus have the potential to treat SANFH. Through the analysis of the competing endogenous RNA network mediated by SANFH-related long non-coding RNAs, potential disease targets, signaling pathways, and potential therapeutic traditional Chinese medicines can be identified, providing a reference for further clarifying its pathogenesis in subsequent experimental research. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the two main types of non-coding RNAs that play crucial roles in plant growth and development. However, their specific roles in the fiber growth of ramie plant (Boehmeria nivea L. Gaud) remain largely unknown. Methods: In this study, we performed miRNA and whole-transcriptome sequencing of two stem bark sections exhibiting different fiber growth stages to determine the expression profiles of miRNAs, lncRNAs, and protein-encoding genes. Results: Among the identified 378 miRNAs and 6,839 lncRNAs, 88 miRNAs and 1,288 lncRNAs exhibited differential expression. Bioinformatics analysis revealed that 29 and 228 differentially expressed protein-encoding genes were targeted by differentially expressed miRNAs and lncRNAs, respectively, constituting eight putative competing endogenous RNA networks. lncR00022274 exhibited downregulated expression in barks with growing fibers. It also had an antisense overlap with the MYB gene, BntWG10016451, whose overexpression drastically increased the xylem fiber number and secondary wall thickness of fibers in the stems of transgenic Arabidopsis, suggesting the potential association of lncR00022274-BntWG10016451 expression with fiber growth. Conclusions: These findings provide insights into the roles of ncRNAs in the regulation of fiber growth in ramie, which can be used for the biotechnological improvement of its fiber yield and quality in the future. [ABSTRACT FROM AUTHOR]

The subcellular localization of long non-coding RNA(lncRNA) is closely related to its function. When localized in the nucleus, lncRNA can maintain chromatin structure, regulate gene transcription and participate in variable splicing of mRNA. When localized in the cytoplasm, lncRNA can mediate signal transduction, post-transcriptional regulation, translation and post-translational modification. When localized in the organelles, lncRNA can assist in the function of them. The subcellular localization of lncRNA is closely related to its own sequences and binding proteins. In addition, the development of lncRNA therapy will be facilitated by changing lncRNA subcellular localization in use of constructing Snovector, adding cytosolic localization elements, or techniques like APEX2, which indicates the relationship between the subcellular localization of lncRNA and its function. [ABSTRACT FROM AUTHOR]

Objective(s): Polycystic ovary syndrome (PCOS), the primary cause of anovulatory infertility in women, may change the gene expression profile of cumulus cells. In human ART (assisted reproductive technology), gene expression profiling in cumulus cells, a non-invasive method, may be used to identify the most competent oocytes. We aim to identify key genes according to the networkbased data and assess the suitability of these genes as markers to predict oocyte competence and PCOS diagnosis. Materials and Methods: The GSE34526 microarray dataset was obtained from the Gene Expression Omnibus (GEO) database. The function and pathway enrichment analysis for DEGs were analyzed. A protein-protein interaction (PPI) network analysis and candidate gene screening were conducted. A two-layer network consisting of mRNA and lncRNA was constructed. Expression levels of hub genes were verified using quantitative RT-PCR (qRT-PCR). Results: A total of 2721 DEGs were retained. The PPI network of selected genes associated with the biological process of "cell communication" was analyzed, and the first 10 key genes were determined by degree. Additionally, 2 hub genes and 2 hub lncRNAs, including STAT3, RHOA, GAS5, and LINC01116, were selected from the lncRNA-mRNA network. Finally, expression levels of STAT3, RHOA, GAS5, and LINC01116 were significantly increased in the cumulus cells of PCOS patients compared to the control group (P<0.05). However, there was no significant difference in expression between the pregnant and non-pregnant groups. Conclusion: STAT3, RHOA, GAS5, and LINC01116 may serve as possible diagnostic markers for PCOS. However, further studies on a larger population are needed to validate this finding. [ABSTRACT FROM AUTHOR]

HOXC cluster antisense RNA 3 (HOXC-AS3) is a novel long noncoding RNA (lncRNA) that exhibits aberrant expression patterns in various cancer types. Its expression is closely related to clinicopathological features, demonstrating significant clinical relevance across multiple tumors. And HOXC-AS3 plays multifaceted roles in tumor progression, impacting cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT), autophagy, senescence, tumor growth, and metastasis. In this review, we summarized and comprehensively analyzed the expression and clinical significance of HOXC-AS3 as a diagnostic and prognostic biomarker for malignancies. Additionally, we presented an in-depth update on HOXC-AS3's functions and regulatory mechanisms in cancer pathogenesis. This narrative review underscores the importance of HOXC-AS3 as a promising lncRNA candidate in cancer research and its potential as a predictive biomarker and therapeutic target in clinical applications. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BLCA) is a prevalent urological tumor with high morbidity and mortality. However, BLCA treatment remains challenging due to a lack of effective biomarkers. Long non-coding RNAs (lncRNAs), as active participants in tumor progression are involved in multiple biological regulatory mechanisms, and cuproptosis-related genes participate in the development of cancer. It is important to discover cuproptosis- related lncRNAs for BLCA diagnosis and treatment. Methods: A predictive signature was constructed based on least absolute shrinkage and selection operator regression (LASSO) and Cox regression analyses of the 9 cuproptosis-related lncRNAs. Samples were divided into high-risk group and low-risk group based on their median risk scores to explore their prognosis. Results: This signature is well predictive, as evidenced by the receiver operating characteristic curves (ROC curves) and K-M curves. Based on the nomogram, we were able to visually forecast the survival rates of patients with BLCA at 1-, 3-, and 5-year, and the calibration plots displayed that the actual results were well matched with the predicted 1-, 3-, and 5-year survival rates. Furthermore, BLCA patients in the high-risk group had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score and lower TMB. Finally, we investigated the response of antitumor drugs for BLCA patients in different risk groups, and a statistically significant difference was observed in the sensitivity of those drugs between low- and the high-risk groups. Conclusion: According to the 9 cuproptosis-related lncRNAs, we constructed a signature which can be served as a promising prognostic biomarker for BLCA patients. [ABSTRACT FROM AUTHOR]

Background: Recent studies have implicated dysregulated long non-coding RNA (lncRNA) levels in the pathogenesis of type 2 diabetes (T2D). This study aimed to assess the expression of circulating HOTAIR and uc.48+, examining their correlation with clinical and biochemical variables in T2D patients, pre-diabetic individuals, and healthy controls. Methods: Peripheral blood levels of lncRNAs were quantified using QRT-PCR in 65 T2D patients, 63 prediabetic individuals, and 63 healthy subjects. Pathway enrichment analysis was conducted to explore the functional enrichment of lncRNA-miRNA targets. Results: Analysis revealed a significantly elevated circulating level of HOTAIR in both T2D (P < 0.0001) and pre-diabetic patients (P = 0.04) compared to controls. ROC analysis demonstrated that, at a cutoff value of 9.1, with a sensitivity of 80% and specificity of 62%, HOTAIR could distinguish T2D patients from controls (AUC = 0.723, 95% CI 0.637-0.799, P < 0.0001). Spearman correlation analysis identified a significant positive correlation between HOTAIR expression, HbA1c, and insulin resistance (P < 0.005). MiRNA enrichment analysis indicated significant enrichment of diabetes-related pathways among HOTAIR's miRNA targets. Conversely, no significant difference in uc.48+ circulating levels between groups was observed, but a significant positive correlation emerged between uc.48+ and systolic blood pressure. Conclusions: This study provides evidence that elevated HOTAIR expression levels are associated with T2D progression, suggesting their potential as biomarkers for early diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Helopeltis theivora or the tea mosquito bug (TMB) is reportedly one of the most devastating pests of tea plant (Camellia sinensis) causing threat to the beverage crop. Long non-coding RNAs (lncRNAs) constitute a group of endogenous RNAs that play gene regulatory roles in eukaryotes. In the present study, 9502 lncRNAs were identified from healthy and TMB-infested C. sinensis tissues using high-throughput strand-specific RNA sequencing, out of which 80 lncRNAs got differentially expressed in response to TMB infestation. Determination of genes that could act as potential targets of lncRNAs revealed that the identified lncRNAs could possibly target as many as 5804 genes. Differential gene expression (DGE) analysis led to the identification of 3665 differentially expressed genes (DEGs), of which, the expression of 1767 genes got upregulated and 1898 genes got downregulated during tea plant's response to TMB. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs and lncRNA-target genes have shown that TMB infestation might have triggered transcriptomic reprogramming leading to altered primary and secondary metabolism in C. sinensis. LncRNAs can act as competing endogenous RNAs (ceRNAs) to bind with common microRNA (miRNA) response elements (MREs) involving a competition between mRNAs and lncRNAs. We report 11 lncRNAs competing with 14 mRNAs to bind with 28 miRNAs forming the ceRNA network. The expression of 6 DEGs and 5 differentially expressed lncRNAs (DELs) has been validated by qRT-PCR. [ABSTRACT FROM AUTHOR]

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Colorectal cancer (CRC) at an advanced stage of cancer has a lower 5-year survival rate. Research on the molecular biological mechanisms of CRC is helpful for disease prevention and treatment. Long non-coding RNAs (lncRNAs) were shown to be suitable as therapeutic targets for CRC. Previously, our research team found that LINC01123 promoted proliferation and metastasis in CRC by regulating miR-625-5p and the LIM and SH3 protein 1 (LASP1). Therefore, this study speculated that the molecular sponge effect of LINC01123 on miR-625-5p affected the process of CRC via regulating LASP1. The LINC01123-silenced CRC cell models (using the LOVO and SW480 cells) and xenograft tumor models were established to verify the above conjecture. As a result, it was found that silencing LINC01123 inhibited viability, proliferation, metastasis, and invasion but promoted apoptosis in LOVO and SW480 cells. Additionally, the knockdown of LINC01123 inhibited the LASP1, N-cadherin, PCNA, and Bcl-2 protein levels and raised the E-cadherin, Bax, and Caspase-3 protein levels in vitro. Furthermore, it showed that LINC01123, as a molecular sponge, targeted the miR-625-5p/LASP1 axis. The results of the xenograft tumor assay further verified the above effects of LINCO1123-silenced on tumor growth in vivo. And the miR-625-5p mimics treatment promoted the aforementioned effects of silencing LINC01123 on CRC cells while overexpressing LASP1 has an antagonistic effect to silencing LINC01123. In conclusion, this study suggests that silencing LINC01123 inhibits the process of CRC via sponging to the miR-625-5p/LASP1 axis. This finding hopes to provide research fundamentals on the biological mechanism study of CRC. [ABSTRACT FROM AUTHOR]

Multiple studies have shown that long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of diverse cancers. Cancer susceptibility candidate 19 (CASC19), encoded by chromosome 8q24.21, is a newly discovered lncRNA that contains 324 nucleotides. CASC19 has been found to be significantly overexpressed in different human cancers, such as non-small cell lung carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, clear cell renal cell carcinoma, glioma, cervical cancer, and nasopharyngeal carcinoma. Moreover, dysregulation of CASC19 was closely associated with clinicopathological parameters and cancer progression. CASC19 regulates a variety of cell phenotypes, including cell proliferation, apoptosis, cell cycle, migration, invasion, epithelial–mesenchymal transition, autophagy, and therapeutic resistance. In this study, we review recent studies on the characteristics and biological function of CASC19, as well as its role in human cancers. These findings suggest that CASC19 may be both a reliable biomarker and a potential therapeutic target in cancers. [ABSTRACT FROM AUTHOR]

Doxorubicin is one of the most classical chemotherapeutic drugs for the treatment of cancer. However, resistance to the cytotoxic effects of doxorubicin in tumor cells remains a major obstacle. Aberrant expression of long non-coding RNAs (lncRNAs) has been associated with tumorigenesis and development via regulation of chromatin remodeling, transcription, and posttranscriptional processing. Emerging studies have also revealed that dysregulation of lncRNAs mediates the development of drug resistance through multiple molecules and pathways. In this review, we focus on the role and mechanism of lncRNAs in the progress of doxorubicin resistance in various cancers, which mainly include cellular drug transport, cell cycle disorder, anti-apoptosis, epithelial-mesenchymal transition, cancer stem cells, autophagy, tumor microenvironment, metabolic reprogramming and signaling pathways. This review is aimed to provide potential therapeutic targets for future cancer therapy, especially for the reversal of chemoresistance. [ABSTRACT FROM AUTHOR]

Objective To construct a prognostic model for breast cancer based on cuproptosis-related long non-coding RNA (lncRNA) and to validate its efficacy. Methods The transcriptional data and clinical information of female patients with breast cancer were obtained from the Cancer Genome Atlas (TCGA) database, and cuproptosis-related lncRNAs in breast cancer were identified by Pearson correlation analysis. Breast cancer patients with complete cuproptosis related lncRNA and clinical data were taken as an overall group and were randomly divided into the training group and validation group at a ratio of 1: 1. The cuproptosis-related lncRNAs which were closely related to the prognosis of breast cancer patients were screened out by univariate Cox regression analysis and LASSO regression analysis in the training group. The multivariate Cox regression analysis was used to construct a prognostic model in breast cancer based on the above-selected lncRNAs, and then the optimal prognostic model (with the smallest AIC value) was selected based on the AIC value. Risk scores were calculated for each patient based on the optimal breast cancer prognostic model. The median risk score of the patients in the training group was used as a cut-off value to categorize all patients into high- and low-risk groups. The differentiation ability of the prognostic model was validated by survival curves and subgroup survival analysis. The accuracy of the prognostic model was validated by receiver operator characteristic (ROC) and consistency index curves. The independence of prognostic models was verified by univariate and multivariate Cox regression. The clinical utility of the prognostic model was verified by Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis of differentially expressed genes in the high- and low-risk groups, and immune infiltration analysis of patients in the high- and low-risk groups. Results The breast cancer prognostic model was constructed by 10 cuproptosis-related lncRNAs (AKT3. IT1, AL137847. 1, AL807757. 2, AC079766. 1, AL451123. 1, LINC02043, AL683813. 1, AC073127. 1, MFF. DT and AC091588. 1). The model formula was risk score = (-1. 129 216 501 573 150×expression of AKT3. IT1) + (-1. 166 095 685 256 72×expression of AL137847. 1) + (0. 729 804 497 137 164×expression of LINC02043)+ (0. 745 696 645 441 295×expression of AL683813. 1)+ (-0. 903 562 388 041 113×expression of AL807757. 2) + (1. 040 608 675 397 110×expression of AC073127. 1) + (2. 160 133 554 898 460×expression of MFF. DT) + (1. 417 144 256 517 410×expression of AC091588. 1) + (-0. 764 700 719 748 750×expression of AC079766. 1) + (-3. 608 177 447 126 010×expression of AL451123. 1). The survival curves demonstrated that patients in the high-risk group had a lower survival rate (P<0. 001). Subgroup survival analysis showed that there was significant difference in prognosis of breast cancer patients in different clinical stages, except for the M1 stage between the high- and low-risk groups (P<0. 05). ROC curves showed that the area under the curve of the model for 1-, 3-, and 5-year survival was 0. 807, 0. 739, and 0. 709, respectively. The multivariate ROC curves and the concordance index curves showed that the predictive efficacy of the risk score was superior to other clinical features. The univariate and multivariate Cox regression analysis showed that risk score was an independent prognostic feature for breast cancer. The differentially expressed genes between the high- and low-risk groups were mainly enriched in immune- and drug resistance-related pathways. Patients in the high-risk group had lower levels of immune cell and stromal cell scores and a higher abundance of M2 macrophage infiltration in comparison with patients in the low-risk group (all P<0. 05). Conclusion The breast cancer prognostic model is constructed based on cuproptosis-related lncRNAs which has good differentiation ability, accuracy, independence, and clinical utility. [ABSTRACT FROM AUTHOR]

Background: Maternal body fluids contain abundant cell-free fetal RNAs which have the potential to serve as indicators of fetal development and pathophysiological conditions. In this context, this study aimed to explore the potential diagnostic value of maternal circulating long non-coding RNAs (lncRNAs) in ventricular septal defect (VSD). Methods: The potential of lncRNAs as non-invasive prenatal biomarkers for VSD was evaluated using quantitative polymerase chain reaction (qPCR) and receiver operating characteristic (ROC) curve analysis. The biological processes and regulatory network of these lncRNAs were elucidated through bioinformatics analysis. Results: Three lncRNAs (LINC00598, LINC01551, and GATA3-AS1) were found to be consistent in both maternal plasma and amniotic fluid. These lncRNAs exhibited strong diagnostic performance for VSD, with AUC values of 0.852, 0.957, and 0.864, respectively. The bioinformatics analysis revealed the involvement of these lncRNAs in heart morphogenesis, actin cytoskeleton organization, cell cycle regulation, and protein binding through a competitive endogenous RNA (ceRNA) network at the post-transcriptional level. Conclusion: The cell-free lncRNAs present in the amniotic fluid have the potential to be released into the maternal circulation, making them promising candidates for investigating epigenetic regulation in VSD. [ABSTRACT FROM AUTHOR]

Background: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms. Methods: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1. Results: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion. Conclusion: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs are ubiquitous throughout the human system, yet many of their biological functions remain unknown. LINC00298 RNA, a long intergenic non-coding RNA, has been shown to have preferential expression in the central nervous system where it contributes to neuronal differentiation and development. Furthermore, previous research has indicated that LINC00298 RNA is known to be a genetic risk factor for the development of Alzheimer's disease. Objective: To biochemically characterize LINC00298 RNA and to elucidate its biological function within hippocampal neuronal cells, thereby providing a greater understanding of its role in Alzheimer's disease pathogenesis. Methods: LINC00298 RNA was in vitro transcribed and then subjected to structural analysis using circular dichroism, and UV-Vis spectroscopy. Additionally, affinity column chromatography was used to capture LINC00298 RNA's protein binding partners from hippocampal neuronal cells, which were then identified using liquid chromatography and mass spectrometry (LC/MS). Results: LINC00298 RNA is comprised of stem-loop secondary structural elements, with a cylindrical tertiary structure that has highly dynamic regions, which result in high positional entropy. LC/MS identified 24 proteins within the interactome of LINC00298 RNA. Conclusion: Through analysis of LINC00298 RNA's 24 protein binding partners, it was determined that LINC00298 RNA may play significant roles in neuronal development, proliferation, and cellular organization. Furthermore, analysis of LINC00298 RNA's interactome indicated that LINC00298 RNA is capable of intracellular motility with dual localization in the nucleus and the cytosol. This biochemical characterization of LINC00298 RNA has shed light on its role in Alzheimer's disease pathogenesis. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play an essential part in controlling gene expression and a variety of biological processes such as immune defense and stress-response. However, whether and how lncRNAs regulate responses of Apis cerana larvae to Ascosphaera apis invasion has remained unclear until now. Here, the identification and structural analysis of lncRNAs in the guts of A. cerana worker larvae were conducted, and the expression profile of larval lncRNAs during the A. apis infection process was then analyzed, followed by an investigation of the regulatory roles of differentially expressed lncRNAs (DElncRNAs) in the host response. In total, 76 sense lncRNAs, 836 antisense lncRNAs, 184 intron lncRNAs, 362 bidirectional lncRNAs, and 2181 intron lncRNAs were discovered in the larval guts. Additionally, 30 known and 9 novel lncRNAs were potential precursors for 36 and 11 miRNAs, respectively. In the three comparison groups, 386, 351, and 272 DElncRNAs were respectively identified, indicating the change in the overall expression pattern of host lncRNAs following the A. apis invasion. Analysis of cis-acting effect showed that DElncRNAs in the 4-, 5-, and 6-day-old comparison groups putatively regulated 55, 30, and 20 up- and down-stream genes, respectively, which were involved in a series of crucial functional terms and pathways, such as MAPK signaling pathway, and cell process. Analysis showed that 31, 8, and 11 DElncRNAs as potential antisense lncRNAs may interact with 26, 8, and 9 sense-strand mRNAs. Moreover, investigation of the competing endogenous RNA (ceRNA) network indicated that 148, 283, and 257 DElncRNAs were putatively regulated. The expression of target genes by targeting corresponding DEmiRNAs included those associated with antioxidant enzymes and immune responses. These results suggested that DElncRNAs played a potential part in the larval guts responding to the A. apis infection through a cis-acting manner and ceRNA mechanisms. Our findings deepen our understanding of interactions between A. cerana larvae and A. apis and offer a basis for clarifying the DElncRNA-mediated mechanisms underlying the host response to fungal invasion. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are non-coding RNA molecules longer than 200 nucleotides that regulate gene expression at the transcriptional, post-transcriptional, and translational levels. Abnormal expression of lncRNAs has been identified in many human diseases. Future improvements in diagnostic, prognostic, and therapeutic techniques will be facilitated by a deeper understanding of disease etiology. Cardiovascular diseases (CVDs) are the main cause of death globally. Cardiac development involves lncRNAs, and their abnormalities are linked to many CVDs. This review examines the relationship and function of lncRNA in a variety of CVDs, including atherosclerosis, myocardial infarction, myocardial hypertrophy, and heart failure. Therein, the potential utilization of lncRNAs in clinical diagnostic, prognostic, and therapeutic applications will also be discussed. [ABSTRACT FROM AUTHOR]

With recent advancements in biological research, long non-coding RNAs (lncRNAs) with lengths exceeding 200 nucleotides have emerged as pivotal regulators of gene expression and cellular phenotypic modulation. Despite initial skepticism due to their low sequence conservation and expression levels, their significance in various biological processes has become increasingly apparent. We provided an overview of lncRNAs and discussed their defining features and modes of operation. We then explored their crucial function in the hepatocarcinogenesis process, elucidating their complex involvement in hepatocellular carcinoma (HCC). The influential role of lncRNAs within the HCC tumor microenvironment is emphasized, illustrating their potential as key modulators of disease dynamics. We also investigated the significant influence of N6-methyladenosine (m6A) modification on lncRNA function in HCC, enhancing our understanding of both their roles and their upstream regulators. Additionally, the potential of lncRNAs as promising biomarkers was discussed in liver cancer diagnosis, suggesting a novel avenue for future research and clinical application. Finally, our work underscored the dual potential of lncRNAs as both contributors to HCC pathogenesis and innovative tools for its diagnosis. Existing challenges and prospective trajectories in lncRNA research are also discussed, emphasizing their potential in advancing liver cancer research. [ABSTRACT FROM AUTHOR]

An effective loss-of-function study is necessary to investigate the biological function of long non-coding RNA (lncRNA). Various approaches are available, including RNA silencing, antisense oligos, and CRISPR-based genome editing. CRISPR-based genome editing is the most widely used for inactivating lncRNA function at the genomic level. Knocking out the lncRNA function can be achieved by removing the promoter and the first exon (PE1), introducing pre-termination poly(A) signals, or deleting the entire locus, unlike frameshift strategies used for messenger RNA (mRNA). However, the intricate genomic interplay between lncRNA and neighbor genes makes it challenging to interpret lncRNA function accurately. This article discusses the advantages and disadvantages of each lncRNA knockout method and envisions the potential future directions to facilitate lncRNA functional study. [ABSTRACT FROM AUTHOR]