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Long non-coding RNAs (lncRNAs) have begun to receive overdue attention for their regulatory roles in gene expression and other cellular processes. Although most lncRNAs are lowly expressed and tissue-specific, notable exceptions include MALAT1 and its genomic neighbor NEAT1, two highly and ubiquitously expressed oncogenes with roles in transcriptional regulation and RNA splicing. Previous studies have suggested that NEAT1 is found only in mammals, while MALAT1 is present in all gnathostomes (jawed vertebrates) except birds. Here we show that these assertions are incomplete, likely due to the challenges associated with properly identifying these two lncRNAs. Using phylogenetic analysis and structure-aware annotation of publicly available genomic and RNA-seq coverage data, we show that NEAT1 is a common feature of tetrapod genomes except birds and squamates. Conversely, we identify MALAT1 in representative species of all major gnathostome clades, including birds. Our in-depth examination of MALAT1, NEAT1, and their genomic context in a wide range of vertebrate species allows us to reconstruct the series of events that led to the formation of the locus containing these genes in taxa from cartilaginous fish to mammals. This evolutionary history includes the independent loss of NEAT1 in birds and squamates, since NEAT1 is found in the closest living relatives of both clades (crocodilians and tuataras, respectively). These data clarify the origins and relationships of MALAT1 and NEAT1 and highlight an opportunity to study the change and continuity in lncRNA structure and function over deep evolutionary time.

AbstractGlioblastoma multiforme (GBM) is an aggressive and diffuse type of glioma with the lowest survival rate in patients. The recent failure of multiple treatments suggests that targeting several targets at once may be a different strategy to overcome GBM carcinogenesis. Normal function of oncogenes and tumor suppressor genes need for the preservation of regular cellular processes, so any defects in these genes’ activity, operate the corresponding signaling pathways, which initiate carcinogenic processes. Long non-coding RNAs (lncRNAs) that can be found in the cytoplasm or nucleus of the cells, control the transcription and translation of genes. LncRNAs perform a variety of functions, including epigenetic alteration, protein modification and stability, transcriptional regulation, and competition for miRNA that regulate mRNA translation through sponging miRNAs. Identification of various oncogenic lncRNAs and their multiple roles in brain cancers making them potential candidates for use as glioma diagnostic, prognostic, and therapeutic targets in the future. This study highlighted multiple oncogenic lncRNAs and classified them into different signaling pathways based on the regulated target genes in glioblastoma. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and are implicated in neurodegenerative diseases, including frontotemporal dementia (FTD). However, their expression patterns and potential as biomarkers in genetic FTD involving Chromosome 9 Open Reading Frame (C9ORF72), Microtubule Associated Protein Tau (MAPT), and Progranulin (GRN) genes are not well understood. Objective: This study aimed to profile the expression levels of lncRNAs in peripheral blood mononuclear cells collected within the GENetic Frontotemporal dementia Initiative (GENFI). Methods: Fifty-three lncRNAs were analyzed with the OpenArray Custom panel, in 131 patients with mutations in C9ORF72, MAPT, and GRN, including 68 symptomatic mutation carriers (SMC) and 63 presymptomatic mutation carriers (PMC), compared with 40 non-carrier controls (NC). Results: Thirty-eight lncRNAs were detectable; the relative expression of NEAT1 and NORAD was significantly higher in C9ORF72 SMC as compared with NC. GAS5 expression was instead significantly lower in the GRN group versus NC. MAPT carriers showed no significant deregulations. No significant differences were observed in PMC. Disease duration did not correlate with lncRNA expression. Conclusions: NEAT1 and NORAD are upregulated in C9ORF72 SMC and GAS5 levels are downregulated in GRN SMC, underlining lncRNAs' relevance in FTD and their potential for biomarker development. Further validation and mechanistic studies are crucial for clinical implications. [ABSTRACT FROM AUTHOR]

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

Breast cancer is a heterogeneous disease that arises as a multi-stage process involving multiple cell types. Patients diagnosed with the same clinical stage and pathological classification may have different prognoses and therapeutic responses due to alterations in molecular genetics. As an essential marker for the molecular subtyping of breast cancer, long non-coding RNAs (lncRNAs) play a crucial role in gene expression regulation, cell differentiation, and the maintenance of genomic stability. Here, we developed a modular framework for lncRNA identification and applied it to a breast cancer cohort to identify novel lncRNAs not previously annotated. To investigate the potential biological function, regulatory mechanisms, and clinical relevance of the novel lncRNAs, we elucidated the genomic and chromatin features of these lncRNAs, along with the associated protein-coding genes and putative enhancers involved in the breast cancer regulatory networks. Furthermore, we uncovered that the expression patterns of novel and annotated lncRNAs identified in breast cancer were related to the hormone response in the PAM50 subtyping criterion, as well as the immune response and progression states of breast cancer across different immune cells and immune checkpoint genes. Collectively, the comprehensive identification and functional analysis of lncRNAs revealed that these lncRNAs play an essential role in breast cancer by altering gene expression and participating in the regulatory networks, contributing to a better insight into breast cancer heterogeneity and potential avenues for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative pathology whose pathognomonic hallmarks are increased generation of β-amyloid (Aβ) peptide, production of hyperphosphorylated (pTau), and neuroinflammation. The last is an alteration closely related to the progression of AD and although it is present in multiple neurodegenerative diseases, the pathophysiological events that characterize neuroinflammatory processes vary depending on the disease. In this article, we focus on mRNA and non-coding RNA alterations as part of the pathophysiological events characteristic of neuroinflammation in AD and the influence of these alterations on the course of the disease through interaction with multiple RNAs related to the generation of Aβ, pTau, and neuroinflammation itself. [ABSTRACT FROM AUTHOR]

Background: To investigate the role of lncRNA LINC00665 in modulating ovarian cancer stemness and its influence on treatment resistance and cancer development. Methods: We isolated ovarian cancer stem cells (OCSCs) from the COC1 cell line using a combination of chemotherapeutic agents and growth factors, and verified their stemness through western blotting and immunofluorescence for stem cell markers. Employing bioinformatics, we identified lncRNAs associated with ovarian cancer, with a focus on LINC00665 and its interaction with the CNBP mRNA. In situ hybridization, immunohistochemistry, and qPCR were utilized to examine their expression and localization, alongside functional assays to determine the effects of LINC00665 on CNBP. Results: LINC00665 employs its Alu elements to interact with the 3'-UTR of CNBP mRNA, targeting it for degradation. This molecular crosstalk enhances stemness by promoting the STAU1-mediated decay of CNBP mRNA, thereby modulating the Wnt and Notch signaling cascades that are pivotal for maintaining CSC characteristics and driving tumor progression. These mechanistic insights were corroborated by a series of in vitro assays and validated in vivo using tumor xenograft models. Furthermore, we established a positive correlation between elevated CNBP levels and increased disease-free survival in patients with ovarian cancer, underscoring the prognostic value of CNBP in this context. Conclusions: lncRNA LINC00665 enhances stemness in ovarian cancer by mediating the degradation of CNBP mRNA, thereby identifying LINC00665 as a potential therapeutic target to counteract drug resistance and tumor recurrence associated with CSCs. [ABSTRACT FROM AUTHOR]

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

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

Background: Long non-coding RNAs (lncRNAs) play various roles in gene regulation. GATA3 antisense RNA 1 (GATA3-AS1) is an lncRNA gene neighboring GATA binding protein 3 (GATA3). The current study aims to quantitatively compare the levels of the expression of GATA3-AS1, GATA3, and Interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) samples of MS patients and healthy individuals under the hypothesis of regulation of GATA3 and IL-4 expression orchestrated by GATA3-AS1. Methods and results: In this case-control study, the GATA3-AS1, GATA3 and IL-4 expression profiles were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Also, we assessed the IL-4 levels in the serum. The median fold changes in MS patients vs. controls were (4.39 ± 0.38 vs. 2.44 ± 0.20) for GATA3-AS1, (5.22 ± 0.51 vs. 2.86 ± 0.30) for GATA3, and (6.16 ± 0.52 vs. 3.57 ± 0.38) for IL-4, (P < 0.001). Furthermore, the mean serum levels of IL-4 were 30.85 ± 1.53 pg/ml in MS patients and 11.15 ± 4.23 pg/ml in healthy controls (P < 0.001). ROC curve analysis showed that the level of GATA3-AS1 might serve as a biomarker for diagnosing MS patients with the area under the curve (AUC = 0.918, P < 0.0001). Based on our results, this GATA3-AS1/GATA3/IL-4 pathway may increase IL-4 expression in MS patients. Conclusions: Our results indicate a probably regulatory function for GATA3-AS1and the levels of GATA3-AS1 in blood could be important biomarkers for MS diagnosis. To confirm and be more certain of these results, it is necessary to study neuromyelitis optica (NMO) and asthma patients in future studies. [ABSTRACT FROM AUTHOR]

The lack of diagnostic markers limits the window of effectiveness for rheumatoid arthritis (RA) therapies. Here, we isolated exosomes of serum samples from four distinct groups RA patients, according to disease activity and with/without medication. Then, total RNA of exosomes was extracted for wholetranscriptome sequencing. Focusing on lncRNA sequencing, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed. We found that the number of upregulated lncRNAs were significantly higher than that of downregulated lncRNAs in each four RA groups. And most importantly, we identified two specific lncRNAs from differentially expressed lncRNAs, TCONS_;I2_;00013502 (up-regulated) and ENST00000363624 (down-regulated) in RA. Receiver Operating Characteristic (ROC) curve analysis showed that the two lncRNAs were promising biomarkers for RA diagnosis. These findings highlight lncRNAs of the serum exosome are important biomarkers and provide application potential for diagnosis of RA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Long non-coding RNAs (lncRNAs), as important regulators of the inflammatory response, are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE: To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways, pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS: PubMed was searched using the search terms of “ischemic stroke, long non-coding RNA, neuroinflammation, immune function, signal pathway, microglia, astrocytes, oligodendrocyte, mechanism,” and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION: In the early stage of ischemic stroke, the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain, promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses. As an important pathogenesis factor in ischemic stroke, the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke, and it needs to be suppressed promptly in the early stage. Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia, astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects. LncRNAs, as important regulatory factors of the inflammatory response, inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB, lncRNA-miRNA-mRNA axis, Rho-ROCK, MAPK, AKT, ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke. Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model, but no clinical trials have been conducted. Therefore, it remains to be further explored about whether lncRNAs can be safely applied in clinical practice. At present, there are many therapeutic drugs for the treatment of ischemic stroke, but there are relatively few studies on the application of lncRNAs, exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology, which need to be further explored. lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity. In future studies, more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored, in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is the most common form of dementia. Currently, there is no single test that can diagnose AD, especially in understudied populations and developing countries. Instead, diagnosis is based on a combination of medical history, physical examination, cognitive testing, and brain imaging. Exosomes are extracellular nanovesicles, primarily composed of RNA, that participate in physiological processes related to AD pathogenesis such as cell proliferation, immune response, and neuronal and cardiovascular function. However, the identification and understanding of the potential role of long non-coding RNAs (lncRNAs) in AD diagnosis remain largely unexplored. Here, we clinically, cognitively, and genetically characterized a sample of 15 individuals diagnosed with AD (cases) and 15 controls from Barranquilla, Colombia. Advanced bioinformatics, analytics and Machine Learning (ML) techniques were used to identify lncRNAs differentially expressed between cases and controls. The expression of 28,909 lncRNAs was quantified. Of these, 18 were found to be differentially expressed and harbored in pivotal genes related to AD. Two lncRNAs, ENST00000608936 and ENST00000433747, show promise as diagnostic markers for AD, with ML models achieving > 95% sensitivity, specificity, and accuracy in both the training and testing datasets. These findings suggest that the expression profiles of lncRNAs could significantly contribute to advancing personalized AD diagnosis in this community, offering promising avenues for early detection and follow-up. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of long non-coding RNA (lncRNA) -AFAP1-AS1 and microRNA (miR) -195-5p on the biological behavior of hepatocellular carcinoma (HCC) cells. Methods Human HCC cell lines (HepG2, Hep3B, SMMC-7721, Bel7402, SK-hep1 cells) and normal human liver cells (HL-7702 cells) were routinely cultured. The expression levels of AFAP1-AS1 and miR-195-5p were detected by real-time fluorescence quantitative PCR to select the experimental cells. The experimental cells in logarithmic growth phase were randomly assigned to different groups： si-AFAP1-AS1 group, si-NC group, miR-195-5p mimics group, mimics-NC group, miR-195-5p inhibitor+si-NC group, miR-195-5p inhibitor+si-AFAP1-AS1 group, inhibitor-NC+si-AFAP1-AS1 group, and inhibitor-NC+si-NC group, respectively. Subsequently, the corresponding plasmids were transfected into the cells using Lipofectamine 2000 reagent based on the grouping. Cell proliferation was assessed by CCK-8 and colony formation experiments, while apoptosis and cell cycle were analyzed using flow cytometry. Cell migration and invasion capabilities were evaluated by Transwell experi­ment, and the targeted relationship between AFAP1-AS1 and miR-195-5p was confirmed via dual luciferase reporter gene assay. Results In HCC cells, AFAP1-AS1 expression was higher than that in normal liver cells (P<0. 05), while miR195-5p expression was lower than that of the normal liver cells (P<0. 05) . Given that SK-hep1 cells exhibited the highest AFAP1-AS1 expression and the lowest miR-195-5p expression, subsequent investigations were carried out using SK-hep1 cells for experimental purposes. Compared with the si-NC group, the si-AFAP1-AS1 group displayed reduced AFAP1-AS1 expression, decreased cell proliferation capacity, reduced migration and invasion cells, a higher cell population in the G0/ G1 phase, and an elevated apoptosis rate (all P<0. 05) . The Starbase v3. 0 online database predicted that there were complementary binding sites between AFAP1-AS1 and miR-195-5p. Findings from the dual-luciferase reporter gene assay indicated that there was significant difference in the relative luciferase activity between the miR-NC and miR-195-5p after cotransfection of WT-AFAP1-AS1 (P<0. 05), while no significant difference was found after co-transfection of MUT-AFAP1- AS1 (P>0. 05) . Compared with the inhibitor-NC+si-NC group, the si-NC+miR-195-5p inhibitor group demonstrated enhanced cell proliferation, increased migration and invasion, reduced cell population in the G0/G1 phase, and decreased apoptosis rate (all P<0. 05) . Conversely, the si-AFAP1-AS1+miR-195-5p inhibitor group exhibited the opposite cellular responses. Conclusion The lncRNA AFAP1-AS1 potentially plays a role in regulating various biological processes in HCC cells, including proliferation, migration, invasion, and apoptosis, through its competitive interaction with miR-195-5p. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression alterations of long non-coding RNA (LncRNA) long intergenic non-coding RNA 00342（LINC00342), and microRNA-596（miR-596) in the gastric cancer tissues and their relationships with the clinicopathological parameters and prognosis. Methods Ninety-three gastric cancer patients were selected, and we obtained the gastric cancer tissues and adjacent cancer tissues in the surgery. Real-time fluorescence quantitative PCR was used to detect the expression levels of LncRNA LINC00342 and miR-596. The binding sites of LncRNA LINC00342 and miR-596 were predicted by starBase database, and the correlation between the expression of LncRNA LINC00342 and miR-596 in gastric cancer tissues was analyzed by Pearson correlation. The relationship between the expression levels of LncRNA LINC00342 and miR-596 in gastric cancer tissues and clinical pathological parameters was analyzed. The gastric cancer patients were followed up after surgery. Gastric cancer tissues were divided into high/low expression groups according to the mean values of LncRNA LINC00342 and miR-596, and the 3-year survival rates of patients with high/low expression of LncRNA LINC00342 and miR-596 were plotted using the Kaplan-Meier method. Cox regression model was used to analyze the influence of the expression levels of LncRNA LINC00342 and miR-596 on the prognosis of gastric cancer patients. Results Compared with the adjacent tissues, the expression of LncRNA LINC00342 was higher and the expression of miR-596 was lower in the gastric cancer tissues (both P<0. 05) . The starBase database predicted that there was a complementary sequence between LncRNA LINC00342 and the 3' untranslated end of miR-596, and the expression of LncRNA LINC00342 and miR-596 was negatively correlated in gastric cancer tissues (r＝－0. 777，P<0. 05) . LncRNA LINC00342 and miR-596 expression levels were associated with the degree of differentiation, TNM stage and lymph node metastasis of gastric cancer (all P<0. 05) . Thirty-six out of 93 gastric cancer patients died, and the 3-year overall survival rate was 61. 29% (57/93) . Compared with patients with high expression of LncRNA LINC00342, the 3-year overall survival rate of gastric cancer patients with low expression of LncRNA LINC00342 was higher (P<0. 05) . Compared with patients with low expression of miR-596, the 3-year overall survival rate of gastric cancer patients with high expression of miR-596 was higher (P<0. 05) . Low differentiation, TNM stage III, lymph node metastasis, and LncRNA LINC00342 ≥ 1. 52 were the independent risk factors for the prognosis of gastric cancer patients (all P<0. 05), and miR-596 ≥ 0. 82 was the independent protective factor (P<0. 05) . Conclusion LncRNA LINC00342 is highly expressed and miR-596 is low expressed in the gastric cancer tissues, and the expression changes of both are related to the degree of tissue differentiation, TNM staging, lymph node metastasis, and prognosis. [ABSTRACT FROM AUTHOR]

Adipocytes are crucial for maintaining energy balance. Adipocyte differentiation involves distinct stages, including the orientation stage, clone amplification stage, clone amplification termination stage, and terminal differentiation stage. Understanding the regulatory mechanisms governing adipogenic differentiation is essential for comprehending the physiological processes and identifying potential biomarkers and therapeutic targets for metabolic diseases, ultimately improving glucose and fat metabolism. Adipogenic differentiation is influenced not only by key factors such as hormones, the peroxisome proliferator-activated receptor (PPAR) family, and the CCATT enhancer-binding protein (C/EBP) family but also by noncoding RNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Among these, lncRNA has been identified as a significant regulator in adipogenic differentiation. Research has demonstrated various ways in which lncRNAs contribute to the molecular mechanisms of adipogenic differentiation. Throughout the adipogenesis process, lncRNAs modulate adipocyte differentiation and development by influencing relevant signaling pathways and transcription factors. This review provides a brief overview of the function and mechanism of lncRNAs in adipogenic differentiation. [ABSTRACT FROM AUTHOR]

Our understanding of RNA biology has evolved with recent advances in research from it being a non-functional product to molecules of the genome with specific regulatory functions. Competitive endogenous RNA (ceRNA), which has gained prominence over time as an essential part of post-transcriptional regulatory mechanism, is one such example. The ceRNA biology hypothesis states that coding RNA and non-coding RNA co-regulate each other using microRNA (miRNA) response elements. The ceRNA components include long non-coding RNAs, pseudogene and circular RNAs that exert their effect by interacting with miRNA and regulate the expression level of its target genes. Emerging evidence has revealed that the dysregulation of the ceRNA network is attributed to the pathogenesis of various cancers, including the head and neck squamous cell carcinoma (HNSCC). This is the most prevalent cancer developed from the mucosal epithelium in the lip, oral cavity, larynx and pharynx. Although many efforts have been made to comprehend the cause and subsequent treatment of HNSCC, the morbidity and mortality rate remains high. Hence, there is an urgent need to understand the holistic progression of HNSCC, mediated by ceRNA, that can have immense relevance in identifying novel biomarkers with a defined therapeutic intervention. In this review, we have made an effort to highlight the ceRNA biology hypothesis with a focus on its involvement in the progression of HNSCC. For the identification of such ceRNAs, we have additionally highlighted a number of databases and tools. [ABSTRACT FROM AUTHOR]

Poplar coma, the fluff-like appendages of seeds originating from the differentiated surface cells of the placenta and funicle, aids in the long-distance dispersal of seeds in the spring. However, it also poses hazards to human safety and causes pollution in the surrounding environment. Unraveling the regulatory mechanisms governing the initiation and development of coma is essential for addressing this issue comprehensively. In this study, strand-specific RNA-seq was conducted at three distinct stages of coma development, revealing 1888 lncRNAs and 52,810 mRNAs. The expression profiles of lncRNAs and mRNAs during coma development were analyzed. Subsequently, potential target genes of lncRNAs were predicted through co-localization and co-expression analyses. Integrating various types of sequencing data, lncRNA-miRNA-TF regulatory networks related to the initiation of coma were constructed. Utilizing identified differentially expressed genes encoding kinesin and actin, lncRNA-miRNA-mRNA regulatory networks associated with the construction and arrangement of the coma cytoskeleton were established. Additionally, relying on differentially expressed genes encoding cellulose synthase, sucrose synthase, and expansin, lncRNA-miRNA-mRNA regulatory networks related to coma cell wall synthesis and remodeling were developed. This study not only enhances the comprehension of lncRNA but also provides novel insights into the molecular mechanisms governing the initiation and development of poplar coma. [ABSTRACT FROM AUTHOR]

Early‐life stress (ES) induced by maternal separation (MS) remains a proven causality of anxiety and memory deficits at later stages of life. Emerging studies have shown that MS‐induced gene expression in the hippocampus is operated at the level of transcription. However, the extent of involvement of non‐coding RNAs in MS‐induced behavioural deficits remains unexplored. Here, we have investigated the role of synapse‐enriched long non‐coding RNAs (lncRNAs) in anxiety and memory upon MS. We observed that MS led to an enhancement of expression of the lncRNA growth arrest specific 5 (Gas5) in the hippocampus; accompanied by increased levels of anxiety and deficits in spatial memory. Gas5 knockdown in early life was able to reduce anxiety and partially rescue the spatial memory deficits of maternally separated adult mice. However, the reversal of MS‐induced anxiety and memory deficits is not attributed to Gas5 activity during neuronal development as Gas5 RNAi did not influence spine development. Gene Ontology analysis revealed that Gas5 exerts its function by regulating RNA metabolism and translation. Our study highlights the importance of MS‐regulated lncRNA in anxiety and spatial memory. [ABSTRACT FROM AUTHOR]

Apoptosis can be known as a key factor in the pathogenesis of neurodegenerative disorders. In disease conditions, the rate of apoptosis expands and tissue damage may become apparent. Recently, the scientific studies of the non-coding RNAs (ncRNAs) has provided new information of the molecular mechanisms that contribute to neurodegenerative disorders. Numerous reports have documented that ncRNAs have important contributions to several biological processes associated with the increase of neurodegenerative disorders. In addition, microRNAs (miRNAs), circular RNAs (circRNAs), as well as, long ncRNAs (lncRNAs) represent ncRNAs subtypes with the usual dysregulation in neurodegenerative disorders. Dysregulating ncRNAs has been associated with inhibiting or stimulating apoptosis in neurodegenerative disorders. Therefore, this review highlighted several ncRNAs linked to apoptosis in neurodegenerative disorders. CircRNAs, lncRNAs, and miRNAs were also illustrated completely regarding the respective signaling pathways of apoptosis. [ABSTRACT FROM AUTHOR]

Epithelial mesenchymal transition (EMT) occurring in retinal pigment epithelial cells (RPE) is a crucial mechanism that contributes to the development of age-related macular degeneration (AMD), a pivotal factor leading to permanent vision impairment. Long non-coding RNAs (lncRNAs) have emerged as critical regulators orchestrating EMT in RPE cells. In this study, we explored the function of the lncRNA CYTOR (cytoskeleton regulator RNA) in EMT of RPE cells and its underlying mechanisms. Through weighted correlation network analysis, we identified CYTOR as an EMT-related lncRNA associated with AMD. Experimental validation revealed that CYTOR orchestrates TGF-β1-induced EMT, as well as proliferation and migration of ARPE-19 cells. Further investigation demonstrated the involvement of CYTOR in regulating the WNT5A/NFAT1 pathway and NFAT1 intranuclear translocation in the ARPE-19 cell EMT model. Mechanistically, CHIP, EMSA and dual luciferase reporter assays confirmed NFAT1's direct binding to CYTOR's promoter, promoting transcription. Reciprocally, CYTOR overexpression promoted NFAT1 expression, while NFAT1 overexpression increased CYTOR transcription. These findings highlight a mutual promotion between CYTOR and NFAT1, forming a positive feedback loop that triggers the EMT phenotype in ARPE-19 cells. These discoveries provide valuable insights into the molecular mechanisms of EMT and its association with AMD, offering potential avenues for targeted therapies in EMT-related conditions, including AMD. [ABSTRACT FROM AUTHOR]

The hypothalamus is an essential neuroendocrine area in animals that regulates sexual development. Long non-coding RNAs (lncRNAs) are hypothesized to regulate physiological processes related to animal reproduction. However, the regulatory mechanism by which lncRNAs participate in sexual maturity in goats is poorly known, particularly from birth to sexual maturation. In this study, RNAseq analysis was conducted on the hypothalamus of four developmental stages (1day (D1, n = 5), 2 months (M2, n = 5), 4months (M4, n = 5), and 6 months (M6, n = 5)) of Jining grey goats. The results showed that a total of 237 differentially expressed lncRNAs (DELs) were identified in the hypothalamus. Among these, 221 DELs exhibited cis-regulatory effects on 693 target genes, while 24 DELs demonstrated trans-regulatory effects on 63 target genes. The target genes of these DELs are mainly involved in biological processes related to energy metabolism, signal transduction and hormone secretion, such as sphingolipid signaling pathway, adipocytokine signaling pathway, neurotrophic signaling pathway, glutamatergic synapse, P53 signaling pathway and GnRH signaling pathway. In addition, XR_001918477.1, TCONS_00077463, XR_001918760.1, and TCONS_00029048 and their potential target genes may play a crucial role in the process of goat sexual maturation. This study advances our understanding of lncRNA in hypothalamic tissue during sexual maturation in goats and will give a theoretical foundation for improving goat reproductive features. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of long non-coding RNA (IncRNA) nuclear-enriched abundant transcript 1 (NEAT1) on the proliferation and apoptosis of human laryngeal squamous cell carcinoma (LSCC) cells, as well as its targeted relationship with microRNA-214 (miR-214). Methods Real-time fluorescence quantitative PCR (RT-qP-CR) was used to detect IncRNA NEATI and miR-214 in immortalized human epidermal cells Hacat and human LSCC cell lines (FD-LSC-1, Hep-2, and TU177), and then TU177 cells were selected as the experimental cells. TU177 cells in the logarithmic growth phase were divided into groups A and B, which were transfected with si-IncRNA NEATI (knockdown of IncRNA NEATI expression) and si-NC (random meaningless sequence), respectively. At 24 h, cell proliferation was observed using CCK-8 assay, colony formation experiment was conducted to observe clone formation, flow cytometry was used to analyze cell cycle distribution and apoptosis rate, while RT-qPCR was performed to detect IncRNA NEATI and miR-214 expression in both groups. TU177 cells in the logarithmic growth phase were divided into groups I, II, III and IV, which were transfected with WT-IncRNA NEAT1 and miR-214 mimic, WT-IncRNA NEATI and miR-NC, MUT-IncRNA NEAT1 and miR-214 mimic, and MUT-IncRNA NEAT1 and miR-NC, respectively. Th targeted relationship between In-CRNA NEATI and miR-214 was validated by dual luciferase reporter gene assay. Results Compared with the group B, the OD values of TU177 cells were lower at 24, 48, and 72 h of cultivation; at 14 d of cultivation, the number of clone formation in TU177 cells was smaller; the proportion of cells in the Go/G, phase was higher, the proportion of cells in the S phase was lower, and the apoptosis rate was higher in the group A (all P<0.05). Compared with the group B, at 24 h of transfection, the relative expression of IncRNA NEATI was lower and the relative expression of miR-214 in TU177 cells was higher in the group A (both P<0.05). At 48 h of cultivation, the luciferase activity of TU 177 cells in the groups I, II, III and IV was 0.63±0.08, 0.99 ±0.01, 1.02 ± 0.02, and 0.98 ± 0.03, respectively. Compared with the group I, group II had lower cell luciferase activity (P<0.05). Conclusions Knockdown of IncRNA NEATI expression can inhibit the proliferation and cloning of TU177 cells, block the cell cycle in Go/G, phase, and promote ote the apoptosis. LncRNA NEATI is targetedly associated with miR-214 in TU177 cells. LncRNA NEATI may inhibit the proliferation and cloning of TU 177 cells, block the cell cycle in Go/G, phase, and promote the apoptosis by targetedly binding with miR-214. [ABSTRACT FROM AUTHOR]

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

Cancer chimeric, or fusion, transcripts are thought to most frequently appear due to chromosomal aberrations that combine moieties of unrelated normal genes. When being expressed, this results in chimeric RNAs having upstream and downstream parts relatively to the breakpoint position for the 5'- and 3'-fusion components, respectively. As many other types of cancer mutations, fusion genes can be of either driver or passenger type. The driver fusions may have pivotal roles in malignisation by regulating survival, growth, and proliferation of tumor cells, whereas the passenger fusions most likely have no specific function in cancer. The majority of research on fusion gene formation events is concentrated on identifying fusion proteins through chimeric transcripts. However, contemporary studies evidence that fusion events involving noncoding RNA (ncRNA) genes may also have strong oncogenic potential. In this review we highlight most frequent classes of ncRNAs fusions and summarize current understanding of their functional roles. In many cases, cancer ncRNA fusion can result in altered concentration of the non-coding RNA itself, or it can promote protein expression from the protein-coding fusion moiety. Differential splicing, in turn, can enrich the repertoire of cancer chimeric transcripts, e.g. as observed for the fusions of circular RNAs and long non-coding RNAs. These and other ncRNA fusions are being increasingly recognized as cancer biomarkers and even potential therapeutic targets. Finally, we discuss the use of ncRNA fusion genes in the context of cancer detection and therapy. [ABSTRACT FROM AUTHOR]

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

Inflammatory bowel disease (IBD) is a group of recurrent chronic inflammatory diseases, including Crohn's disease (CD) and ulcerative colitis (UC). Although IBD has been extensively studied for decades, its cause and pathogenesis remain unclear. Existing research suggests that IBD may be the result of an interaction between genetic factors, environmental factors and the gut microbiome. IBD is closely related to non-coding RNAs (ncRNAs). NcRNAs are composed of microRNA(miRNA), long non-coding RNA(lnc RNA) and circular RNA(circ RNA). Compared with miRNA, the role of lnc RNA in IBD has been little studied. Lnc RNA is an RNA molecule that regulates gene expression and regulates a variety of molecular pathways involved in the pathbiology of IBD. Targeting IBD-associated lnc RNAs may promote personalized treatment of IBD and have therapeutic value for IBD patients. Therefore, this review summarized the effects of lnc RNA on the intestinal epithelial barrier, inflammatory response and immune homeostasis in IBD, and summarized the potential of lnc RNA as a biomarker of IBD and as a predictor of therapeutic response to IBD in the future. [ABSTRACT FROM AUTHOR]

Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms underlying their pathogenesis. In recent years, the focus has shifted toward the intricate world of non-coding RNAs (ncRNAs), a class of RNA molecules that do not encode proteins but play pivotal roles in gene regulation and cellular processes. This review explores the emerging significance of ncRNAs in the context of neurological and neuropsychiatric disorders, shedding light on their diverse functions and regulatory mechanisms. The dysregulation of various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has been implicated in the pathophysiology of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and mood disorders. This review delves into the specific roles these ncRNAs play in modulating key cellular processes, including synaptic plasticity, neuroinflammation, and apoptosis, providing a nuanced understanding of their impact on disease progression. Furthermore, it discusses the potential diagnostic and therapeutic implications of targeting ncRNAs in neurological and neuropsychiatric disorders. The identification of specific ncRNA signatures holds promise for the development of novel biomarkers for early disease detection, while the manipulation of ncRNA expression offers innovative therapeutic avenues. Challenges and future directions in the field are also considered, highlighting the need for continued research to unravel the complexities of ncRNA-mediated regulatory networks in the context of neurological and neuropsychiatric disorders. This review aims to provide a comprehensive overview of the current state of knowledge and stimulate further exploration into the fascinating realm of ncRNAs in the brain's intricate landscape. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most common form of cancer worldwide Research points to the pivotal role of non-coding RNAs (ncRNAs) in controlling and managing the pathology by controlling essential pathways. ncRNAs have all been identified as being either up- or downregulated among individuals suffering from lung cancer thus hinting that they may play a role in either promoting or suppressing the spread of the disease. Several ncRNAs could be effective non-invasive biomarkers to diagnose or even serve as effective treatment options for those with lung cancer, and several molecules have emerged as potential targets of interest. Given that ncRNAs are contained in exosomes and are implicated in the development and progression of the malady. Herein, we have summarized the role of ncRNAs in lung cancer. Moreover, we highlight the role of exosomal ncRNAs in lung cancer. [ABSTRACT FROM AUTHOR]

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

Introduction: Urothelial Bladder Cancer (BC) is the ninth most common cancer worldwide. It is classified into Non Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC), which are characterized by frequent recurrences and progression rate, respectively. The diagnosis and monitoring are obtained through invasive methods as cystoscopy and post-surgery biopsies. Thus, a panel of biomarkers able to discriminate BC based on grading or staging represents a significant step forward in the patients' workup. In this perspective, long non-coding RNAs (lncRNAs) are emerged as reliable candidates as potential biomarker given their specific and regulated expression. In the present work we propose two lncRNAs, the Small Ubiquitin Modifier 1 pseudogene 3 (SUMO1P3), a poorly characterized pseudogene, and the Urothelial Carcinoma Associated 1 (UCA1) as candidates to monitor the BC progression. Methods: This study was a retrospective trial enrolling NMIBC and MIBC patients undergoing surgical intervention: the expression of the lncRNA SUMO1P3 and UCA1 was evaluated in urine from 113 subjects (cases and controls). The receiver operating characteristic curve analysis was used to evaluate the performance of single or combined biomarkers in discriminating cases from controls. Results: SUMO1P3 and UCA1 expression in urine was able to significantly discriminate low grade NMIBC, healthy control and benign prostatic hyperplasia subjects versus high grade NMIBC and MIBC patients. We also demonstrated that miR-320a, which binds SUMO1P3, was reduced in high grade NMIBC and MIBC patients and the SUMO1P3/miR-320a ratio was used to differentiate cases versus controls, showing a statistically significant power. Finally, we provided an automated method of RNA extraction coupled to ddPCR analysis in a perspective of clinical application. Discussion: We have shown that the lncRNA SUMO1P3 is increased in urine from patients with high grade NMIBC and MIBC and that it is likely to be good candidate to predict bladder cancer progression if used alone or in combination with UCA1 or with miRNA320a. [ABSTRACT FROM AUTHOR]

Introduction: Accumulating evidence has proved that long non-coding RNAs (lncRNAs) are involved in progression of glioma. Nevertheless, the role of TUBA4B in glioma remains unclear. Material and methods: The expression of the target gene was measured by quantitative RT-PCR. The prognostic role of TUBA4B was analyzed by Meier survival analysis. Cell proliferation, colony formation, apoptosis, cell cycle, migration and invasion were detected by MTS, soft agar colony forming assay, flow cytometry, and transwell assay. The target interaction of the target gene was validated by the luciferase reporter assay, biotin pull-down assay, and RNA immunoprecipitation. Results: We found that the expression of TUBA4B was lower in glioma tissues and cells. Moreover, patients with a low TUBA4B expression level exhibited poorer prognosis than those with high TUBA4B expression. Meanwhile, ROC analysis revealed that TUBA4B had diagnostic value to distinguish tumor patients from the healthy population. Overexpression of TUBA4B prohibited the malignancy of glioma, such as inhibition of proliferation, decrease of colony formation, arrest of the cell cycle, decline of migration and invasion, and promotion of cell apoptosis. In addition, we found that TUBA4B directly interacted with miR-183 and negatively regulated the expression of miR-183. We also observed that SMAD4 was a downriver target of miR-183 and TUBA4B subsequently exerted its tumor-suppressive effects by coordinating the expression of SMAD4 in glioma. Conclusions: This study revealed for the first time that TUBA4B could be a tumor suppressor gene in glioma by adjustment of the TUBA4B/miR-183/SMAD4 axis, which may provide a useful prognostic biomarker and promising therapeutic target for glioma treatment. [ABSTRACT FROM AUTHOR]

Short-chain fatty acids (SCFAs), derived from fermentation of dietary fibers and resistant starch by the microbiota in the colon, exert multiple effects on colonic functions, including tumor suppressing activities. Our previous studies found that SCFAs induced autophagy in colon cancer cells via downregulating mTOR signaling, but the mechanism involved in mTOR suppression still needs to be defined. In this study, we identified rhabdomyosarcoma 2 associated transcript (RMST), a long non-coding RNA, as a key mediator for SCFAs to suppress mTOR activation in colon cancer cells. RMST could be significantly induced by SCFAs in a time- and dose-dependent manner. RMST, by itself, was sufficient to suppress mTOR signaling and augment autophagosome formation. Depletion of RMST, through siRNA or CRISPR knockdown, reduced the abilities of SCFAs to suppress mTOR activation or to induce autophagic responses. RMST increased the expression level of TSC2, a negative regulator of the mTOR signaling pathway. Our data delineate a novel RMST/TSC2 cellular pathway, enlisted by SCFAs, to modulate mTOR activities in colon cancer cells. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) represent a new group of host factors involved in viral infection. Current study identified an intergenic lncRNA, LINC08148, as a proviral factor of Zika virus (ZIKV) and Dengue virus 2 (DENV2). Knockout (KO) or silencing of LINC08148 decreases the replication of ZIKV and DENV2. LINC08148 mainly acts at the endocytosis step of ZIKV but at a later stage of DENV2. RNA-seq analysis reveals that LINC08148 knockout downregulates the transcription levels of five endocytosis-related genes including AP2B1, CHMP4C, DNM1, FCHO1, and Src. Among them, loss of Src significantly decreases the uptake of ZIKV. Trans-complementation of Src in the LINC08148KO cells largely restores the caveola-mediated endocytosis of ZIKV, indicating that the proviral effect of LINC08148 is exerted through Src. Finally, LINC08148 upregulates the Src transcription through associating with its transcription factor SP1. This work establishes an essential role of LINC08148 in the ZIKV entry, underscoring a significance of lncRNAs in the viral infection. IMPORTANCE Long non-coding RNAs (lncRNAs), like proteins, participate in viral infection. However, functions of most lncRNAs remain unknown. In this study, we performed a functional screen based on microarray data and identified a new proviral lncRNA, LINC08148. Then, we uncovered that LINC08148 is involved in the caveola-mediated endocytosis of ZIKV, rather than the classical clathrin-mediated endocytosis. Mechanistically, LINC08148 upregulates the transcription of Src, an initiator of caveola-mediated endocytosis, through binding to its transcription factor SP1. This study identifies a new lncRNA involved in the ZIKV infection, suggesting lncRNAs and cellular proteins are closely linked and cooperate to regulate viral infection. [ABSTRACT FROM AUTHOR]

Dementia, a multifaceted neurological syndrome characterized by cognitive decline, poses significant challenges to daily functioning. The main causes of dementia, including Alzheimer's disease (AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and vascular dementia (VD), have different symptoms and etiologies. Genetic regulators, specifically non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are known to play important roles in dementia pathogenesis. MiRNAs, small non-coding RNAs, regulate gene expression by binding to the 3′ untranslated regions of target messenger RNAs (mRNAs), while lncRNAs and circRNAs act as molecular sponges for miRNAs, thereby regulating gene expression. The emerging concept of competing endogenous RNA (ceRNA) interactions, involving lncRNAs and circRNAs as competitors for miRNA binding, has gained attention as potential biomarkers and therapeutic targets in dementia-related disorders. This review explores the regulatory roles of ncRNAs, particularly miRNAs, and the intricate dynamics of ceRNA interactions, providing insights into dementia pathogenesis and potential therapeutic avenues. [ABSTRACT FROM AUTHOR]

Aristolochia contorta Bunge is an academically and medicinally important plant species. It belongs to the magnoliids, with an uncertain phylogenetic position, and is one of the few plant species lacking a whole-genome duplication (WGD) event after the angiosperm-wide WGD. A. contorta has been an important traditional Chinese medicine material. Since it contains aristolochic acids (AAs), chemical compounds with nephrotoxity and carcinogenicity, the utilization of this plant has attracted widespread attention. Great efforts are being made to increase its bioactive compounds and reduce or completely remove toxic compounds. MicroRNAs (miRNAs) and natural antisense transcripts (NATs) are two classes of regulators potentially involved in metabolism regulation. Here, we report the identification and characterization of 223 miRNAs and 363 miRNA targets. The identified miRNAs include 51 known miRNAs belonging to 20 families and 172 novel miRNAs belonging to 107 families. A negative correlation between the expression of miRNAs and their targets was observed. In addition, we identified 441 A. contorta NATs and 560 NAT-sense transcript (ST) pairs, of which 12 NATs were targets of 13 miRNAs, forming 18 miRNA-NAT-ST modules. Various miRNAs and NATs potentially regulated secondary metabolism through the modes of miRNA-target gene–enzyme genes, NAT-STs, and NAT-miRNA-target gene–enzyme genes, suggesting the complexity of gene regulatory networks in A. contorta. The results lay a solid foundation for further manipulating the production of its bioactive and toxic compounds. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a rare biliary tract tumor with high malignancy. CCA is the second most common primary hepatobiliary cancer after hepatocarcinoma. Despite its rarity, the incidence of CCA is steadily increasing globally. Most patients with CCA are asymptomatic in the early stages, resulting in a late-stage diagnosis and poor prognosis. Finding reliable biomarkers is essential to improve CCA's early diagnosis and survival rate. Non-coding RNAs (ncRNAs) are non-protein coding RNAs produced by genomic transcription. This includes microRNAs, long non-coding RNAs, and circular RNAs. ncRNAs have multiple functions in regulating gene expression and are crucial for maintaining normal cell function and developing diseases. Many studies have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA. ncRNAs can be easily extracted and detected through tumor tissue and liquid biopsies, representing a potential tool for diagnosing and prognosis CCA. This review will provide a detailed update on the diagnostic and prognostic potentials of lncRNAs and cirRNAs as biomarkers in CCA. [ABSTRACT FROM AUTHOR]

Neuroblastoma is the most common malignant extracranial solid tumor of childhood. Recent studies involving the application of advanced high-throughput "omics" techniques have revealed numerous genomic alterations, including aberrant coding-gene transcript levels and dysfunctional pathways, that drive the onset, growth, progression, and treatment resistance of neuroblastoma. Research conducted in the past decade has shown that long non-coding RNAs, once thought to be transcriptomic noise, play key roles in cancer development. With the recent and continuing increase in the amount of evidence for the underlying roles of long non-coding RNAs in neuroblastoma, the potential clinical implications of these RNAs cannot be ignored. In this review, we discuss their biological mechanisms of action in the context of the central driving mechanisms of neuroblastoma, focusing on potential contributions to the diagnosis, prognosis, and treatment of this disease. We also aim to provide a clear, integrated picture of future research opportunities. [ABSTRACT FROM AUTHOR]

Hoogsteen base pairing enables the association of an RNA strand with a DNA double-helix, allowing the formation of RNA-DNA triplexes, which now have been identified to occur in vivo. Such identifications require specific bioinformatic, biochemical, and biophysical methods, offering experimental opportunities, but also render the field complex. Triplex formation has been best studied for long non-coding RNAs (lncRNAs). Numerous lncRNAs fine-tune gene expression through triplex formation. Many aspects of triplex biology still await clarification, making this research field highly dynamic. Interactions of RNA with DNA are principles of gene expression control that have recently gained considerable attention. Among RNA–DNA interactions are R-loops and RNA-DNA hybrid G-quadruplexes, as well as RNA-DNA triplexes. It is proposed that RNA-DNA triplexes guide RNA-associated regulatory proteins to specific genomic locations, influencing transcription and epigenetic decision making. Although triplex formation initially was considered solely an in vitro event, recent progress in computational, biochemical, and biophysical methods support in vivo functionality with relevance for gene expression control. Here, we review the central methodology and biology of triplexes, outline paradigms required for triplex function, and provide examples of physiologically important triplex-forming long non-coding RNAs. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) develops asymptomatically and escapes diagnosis until advanced stages, the feature contributing to a higher mortality rate. New prospects of OC diagnosis and treatment have been opened in studies of the gene regulation mechanisms that involve long noncoding RNAs (lncRNAs) and identification of the lncRNA genes that are inhibited via methylation of the promoter region. A set of 122 samples of primary OC tumors was examined by methylation specific real-time PCR to assess the methylation level of the lncRNA genes PLUT, SNHG1, SNHG6, SNHG12, and TINCR. A significant increase in their methylation levels was observed in OC (p < 0.001 by the nonparametric Mann–Whitney test). The methylation levels of SNHG6, SNHG12, and TINCR were found to correlate significantly (p < 0.05) with the stage of the tumor process, the histological grade, and metastasis. Downregulation of SNHG6, SNHG12, and TINCR was detected by real-time RT–qPCR, and a significant correlation between methylation and expression was demonstrated for SNHG6 and TINCR (rs ≤ –0.5, p < 0.001). The respective lncRNA genes were assumed to provide potential epigenetic markers of OC. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are involved in many cellular processes while displaying high tissue specificity. In contrast, protein-coding genes, including the category of housekeeping ones, exhibit broad expression patterns. The aim of this study was to highlight the functional importance of widely expressed lncRNAs. We analyzed experimental data from cell-growth screen of lncRNA loci in human cells, which allowed us to identify 18 lncRNA hits. Notably, these lncRNAs were not only widely expressed in most human tissues, but also played functional roles within them. Detail investigation revealed them encompass a variety of molecular functions, from cardiomyocyte damage controlling to macrophage class switching. Interestingly, experimental data highlighted the fact that a significant part of these lncRNAs encoded small but functional polypeptides. A set of lncRNAs, NEAT1, SNHG1, SNHG7, SNHG12, SNHG15, SNHG16, MIR17HG, LINC00680, LINC00263 and LINC00339, that were highly likely to be translated into small polypeptides was identified. Additionally, for EPB41L4A-AS1, CRNDE, SNHG6, LINC00493, and LINC01420, a dual function associated with both the RNA sequences and small proteins they encoded was established. [ABSTRACT FROM AUTHOR]

Pigeon pea (Cajanus cajan) is widely cultivated for its nutritional and medicinal value yet remains an orphan crop as productivity has not been improved because of a lack of genome and non‐coding genome information. Non‐coding RNAs, like miRNAs and long non‐coding RNAs (lncRNAs), are involved in regulation of growth, metabolism, development, and stress response, and have a critical role in post‐transcriptional gene regulation (PTGR).We attempted to elucidate the roles of miRNAs and lncRNAs in pigeon pea through experimental validation of computationally predicted miRNAs and lncRNAs and targets of miRNAs on mRNAs.We experimentally validated 20 miRNAs and 11 lncRNAs. We predicted cleavage sites of three miRNA targets: serine/threonine‐protein kinase, polygalacturonase, beta‐galactosidase. We identified 469 targets of 265 miRNAs and their functional annotations using computational methods. We built a miRNA‐mRNA‐lncRNA network model, with the miRNAs targeting both mRNAs and lncRNAs, to obtain information on the interplay of these three molecules.A confirmed interaction through experimental validation was established between miRNA, namely cca‐miR1535a targeting the mRNA for beta‐galactosidase, as well as the lncRNA cca‐lnc‐020033. Our findings increase knowledge of the non‐coding genome of pigeon pea and their roles in PTGR and in improving agronomic traits of this pulse crop. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer has emerged as the main gynecological malignant tumour in developed countries. The development of molecular techniques allows the precise profiling of each case. This affects the selection of a therapy and the patient's prognosis. Long non-coding RNAs, which influence tumour development, are a novelty in endometrial cancer. They can both stimulate and inhibit the progression of the disease. Their number is constantly growing, and the mechanisms of action are not fully discovered. Some of them may become targets for new molecular therapies in the future. Endometrial cancer is one of the most common malignant tumours in women. The development of this tumour is associated with several genetic disorders, many of which are still unknown. One type of RNA molecules currently being intensively studied in many types of cancer are long non-coding RNAs (lncRNAs). LncRNA-coding genes occupy a large fraction of the human genome. LncRNAs regulate many aspects of cell development, metabolism, and other physiological processes. Diverse types of lncRNA can function as a tumour suppressor or an oncogene that can alter migration, invasion, cell proliferation, apoptosis, and immune system response. Recent studies suggest that selected lncRNAs are important in an endometrial cancer course. Our article describes over 70 lncRNAs involved in the development of endometrial cancer, which were studied via in vivo and in vitro research. It was proved that lncRNAs could both promote and inhibit the development of endometrial cancer. In the future, lncRNAs may become an important therapeutic target. The aim of this study is to review the role of lncRNAs in the development of carcinoma of uterine body. [ABSTRACT FROM AUTHOR]

Background: Acacetin is a natural flavonoid known for its anti-tumor, antioxidant, and anti-inflammatory properties. Our previous studies have shown its protective effects against cerebral ischemia-reperfusion injury (IRI), but the underlying molecular mechanisms remain unclear. Purpose: The study delves into acacetin's mechanism in mitigating cerebral IRI, with a focus on transcriptomic insights. Methods: We established the oxygen-glucose deprivation/re-oxygenation (OGD/R) model in BV2 microglia, treating them with 10μM acacetin. Then we assessed cell proliferation using CCK-8 and measured Lactate Dehydrogenase (LDH) release. High-throughput RNA sequencing (RNA-seq) underpinned the analysis of differentially expressed genes (DEGs) and long non-coding RNAs (lncRNAs), functional enrichment, and alternative splicing events (ASEs), validated by reverse transcription–quantitative polymerase chain reaction (RT-qPCR). Results: OGD/R injury significantly impaired cell proliferation and increased LDH release, effects mitigated by acacetin. RNA-seq identified 2148 upregulated and 2135 downregulated DEGs post-OGD/R. In contrast, the acacetin-treated group showed 248 upregulated and 240 downregulated DEGs compared to the OGD/R group. All DEGs were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Overlapping analysis indicated that acacetin treatment reversed the expression of 203 genes affected by OGD/R, including inflammation-related genes such as Isg15, Fcgr1, Il1b, and Parp12. Moreover, the oxidative stress-related gene, Mt2, was downregulated post-OGD/R but upregulated following acacetin treatment. We further found that OGD/R and acacetin treatment could modulate gene splicing events, impacting cell apoptosis or inflammatory responses, such as the A3SS splicing event in the Trim47 gene. RNA-seq also highlighted differential expression of numerous lncRNAs, particularly the upregulation of lncRNA Rmrp and Terc post-OGD/R and their subsequent downregulation post-acacetin treatment. These lncRNAs might regulate cell proliferation through mediating target gene expressions. RT-qPCR validation confirmed these findings. Conclusion: Significant upregulation of genes and ASEs linked to oxidative stress and inflammatory response is observed in cerebral IRI. Acacetin intervention reverses these effects, highlighting its mechanism in alleviating the injury by modulating gene expression and splicing events. [ABSTRACT FROM AUTHOR]

Main conclusion: The combined transcriptome outcome provides an important clue to the regulatory cascade centering on lncRNA GARR2 and CPS2 gene in GA response. Long non-coding RNAs (lncRNAs) serve as regulatory components in transcriptional hierarchy governing multiple aspects of biological processes. Dissecting regulatory mechanisms underpinning tetracyclic diterpenoid gibberellin (GA) cascade holds both theoretical and applied significance. However, roles of lncRNAs in transcriptional modulation of GA pathway remain largely elusive. Gypsy retrotransposon-derived GIBBERELLIN RESPONSIVE lncRNA2 (GARR2) has been reported as GA-responsive maize lncRNA. Here a novel GARR2-edited line garr2-1 was identified, characteristic of GA-induced phenotype of increased seedling height and elongated leaf sheath. Transcriptome analysis indicated that transcriptional abundance of five genes [ent-copalyl diphosphate synthase2 (CPS2), ent-kaurene synthase4 (KS4), ent-kaurene synthase6 (KS6), ent-kaurene oxidase2 (KO2), and ent-kaurenoic acid oxidase1/Dwarf3 (KAO1/D3)] was elevated in garr2-1 for early steps of GA biosynthesis. Five GA biosynthetic genes as hub regulators were interlaced to shape regulatory network of GA response. Different transcriptome resources were integrated to discover common differentially expressed genes (DEGs) in the independent GARR2-edited lines GARR2KO and garr2-1. A total of 320 common DEGs were retrieved. These common DEGs were enriched in diterpenoid biosynthetic pathway. Integrative transcriptome analysis revealed the common CPS2 encoding the CPS enzyme that catalyzes the conversion of the precursor trans-geranylgeranyl diphosphate to ent-copalyl diphosphate. The up-regulated CPS2 supported the GA-induced phenotype of slender seedlings observed in the independent GARR2-edited lines GARR2KO and garr2-1. Our integrative transcriptome analysis uncovers common components of the GA pathway regulated by lncRNA GARR2. These common components, especially for the GA biosynthetic gene CPS2, provide a valuable resource for further delineating the underlying mechanisms of lncRNA GARR2 in GA response. [ABSTRACT FROM AUTHOR]

It is generally accepted that atherosclerosis is a chronic inflammatory disease. The link between atherosclerosis and other inflammatory diseases such as psoriasis, type 2 diabetes mellitus (T2DM), and rheumatoid arthritis (RA) via metabolic, inflammatory, and immunoregulatory pathways is well established. The aim of our review was to summarize the associations between selected microRNAs (miRs) and long non-coding RNAs (lncRNAs) and atherosclerosis, psoriasis, T2DM, and RA. We reviewed the role of miR-146a, miR-210, miR-143, miR-223, miR-126, miR-21, miR-155, miR-145, miR-200, miR-133, miR-135, miR-221, miR-424, let-7, lncRNA-H19, lncRNA-MEG3, lncRNA-UCA1, and lncRNA-XIST in atherosclerosis and psoriasis, T2DM, and RA. Extracellular vesicles (EVs) are a method of intracellular signal transduction. Their function depends on surface expression, cargo, and the cell from which they originate. The majority of the studies that investigated lncRNAs and some miRs had relatively small sample sizes, which limits the generalizability of their findings and indicates the need for more research. Based on the studies reviewed, miR-146a, miR-155, miR-145, miR-200, miR-133, and lncRNA-H19 are the most promising potential biomarkers and, possibly, therapeutic targets for atherosclerosis as well as T2DM, RA, and psoriasis. [ABSTRACT FROM AUTHOR]

The GeneCaRNA human gene database is a member of the GeneCards Suite. It presents ~280,000 human non-coding RNA genes, identified algorithmically from ~690,000 RNAcentral transcripts. This expands by ~tenfold the ncRNA gene count relative to other sources. GeneCaRNA thus contains ~120,000 long non-coding RNAs (LncRNAs, >200 bases long), including ~100,000 novel genes. The latter have sparse functional information, a vast terra incognita for future research. LncRNA genes are uniformly represented on all nuclear chromosomes, with 10 genes on mitochondrial DNA. Data obtained from MalaCards, another GeneCards Suite member, finds 1547 genes associated with 1 to 50 diseases. About 15% of the associations portray experimental evidence, with cancers tending to be multigenic. Preliminary text mining within GeneCaRNA discovers interactions of lncRNA transcripts with target gene products, with 25% being ncRNAs and 75% proteins. GeneCaRNA has a biological pathways section, which at present shows 131 pathways for 38 lncRNA genes, a basis for future expansion. Finally, our GeneHancer database provides regulatory elements for ~110,000 lncRNA genes, offering pointers for co-regulated genes and genetic linkages from enhancers to diseases. We anticipate that the broad vista provided by GeneCaRNA will serve as an essential guide for further lncRNA research in disease decipherment. [ABSTRACT FROM AUTHOR]

Unsaturated fatty acids (UFAs) in beef play a vital role in promoting human health. Long-chain fatty acyl-CoA synthase 1 (ACSL1) is a crucial gene for UFA synthesis in bovine adipocytes. To investigate the protein expression profile during UFA synthesis, we performed a proteomic analysis of bovine adipocytes by RNA interference and non-interference with ACSL1 using label-free techniques. A total of 3558 proteins were identified in both the NC and si-treated groups, of which 1428 were differentially expressed proteins (DEPs; fold change ≥ 1.2 or ≤ 0.83 and p-value < 0.05). The enrichment analysis of the DEPs revealed signaling pathways related to UFA synthesis or metabolism, including cAMP, oxytocin, fatty acid degradation, glycerol metabolism, insulin, and the regulation of lipolysis in adipocytes (p-value < 0.05). Furthermore, based on the enrichment analysis of the DEPs, we screened 50 DEPs that potentially influence the synthesis of UFAs and constructed an interaction network. Moreover, by integrating our previously published transcriptome data, this study established a regulatory network involving differentially expressed long non-coding RNAs (DELs), highlighting 21 DEPs and 13 DELs as key genes involved in UFA synthesis. These findings present potential candidate genes for further investigation into the molecular mechanisms underlying UFA synthesis in bovines, thereby offering insights to enhance the quality of beef and contribute to consumer health in future studies. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are pivotal regulators of the abiotic stress responses in plants, yet their specific involvement in salt/alkali stress during alfalfa germination remains incompletely understood. Here, we subjected Zhongmu No.1 alfalfa (Medicago sativa L.) seeds to salt stress (20 mM NaCl and 20 mM Na2SO4 solutions) or alkali stress (5 mM NaHCO3 and 5 mM Na2CO3 solutions) treatments for 3 days, followed by total RNA extraction and RNA-seq analysis to delineate stress-responsive alfalfa lncRNAs. We identified 17,473 novel alfalfa lncRNAs, among which 101 and 123 were differentially expressed lncRNAs (DElncRNAs) under salt and alkali stress, respectively, compared to the control. Furthermore, we predicted 16 and 237 differentially expressed target genes regulated by DElncRNAs through cis/trans-regulatory mechanisms under salt or alkali stress, respectively. A functional enrichment analysis of DElncRNA target genes indicated that lncRNAs were implicated in the fatty acid metabolism pathway under salt stress, while they played a significant role in the phenylpropanoid and flavonoid biosynthesis pathway under alkali stress. Notably, lncRNAs were found to participate in the plant hormone signal transduction pathway, a common regulatory mechanism in both salt and alkali stress responses. These findings contribute to a deeper understanding of the mechanisms underlying alfalfa's response to salt and alkali stresses. [ABSTRACT FROM AUTHOR]

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