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Ischemic stroke is a serious cerebrovascular disease, highlighting the urgent need for reliable biomarkers for early diagnosis. Recent reports suggest that long non-coding RNAs (lncRNAs) can be potential biomarkers for ischemic stroke. Therefore, our study seeks to investigate the potential diagnostic value of lncRNAs for ischemic stroke by analyzing existing research. A comprehensive literature search was conducted across the PubMed, ScienceDirect, Wiley Online Library, and Web of Science databases for articles published up to July 10, 2024. Statistical analyses were performed using Stata 17.0 software to calculate pooled sensitivity, specificity, positive likelihood ratio (PLR), diagnostic odds ratio (DOR), negative likelihood ratio (NLR), and area under the curve (AUC). Heterogeneity was explored with the Cochran-Q test and the I2 statistical test, and publication bias was assessed with Deeks' funnel plot. A total of 44 articles were included, involving 4302 ischemic stroke patients and 3725 healthy controls. Results demonstrated that lncRNAs H19, GAS5, PVT1, TUG1, and MALAT1 exhibited consistent trends across multiple studies. The pooled sensitivity of lncRNAs in the diagnosis of ischemic stroke was 79% (95% CI: 73–84%), specificity was 88% (95% CI: 77–94%), PLR was 6.63 (95% CI: 3.11–14.15), NLR was 0.23 (95% CI: 0.16–0.33), DOR was 28.5 (95% CI: 9.88–82.21), and AUC was 0.88 (95% CI: 0.85–0.90). Furthermore, the results of subgroup analysis indicated that lncRNA H19 had superior diagnostic performance. LncRNAs demonstrated strong diagnostic accuracy in distinguishing ischemic stroke patients from healthy controls, underscoring their potential as reliable biomarkers. Because most of the articles included in this study originate from China, large-scale, high-quality, multi-country prospective studies are required to further validate the reliability of lncRNAs as biomarkers for ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) are a group of nanoscale cell-derived membranous structures secreted by all cell types, containing molecular cargoes involved in intercellular communication. EVs can be used to mimic "nature's delivery system" to transport nucleic acids, peptides, lipids, and metabolites to target recipient cells. EVs offer a range of advantages over traditional synthetic carriers, thus paving the way for innovative drug delivery approaches that can be used in different diseases, including cancer. Here, by using breast cancer (BC) cells treated with the multi-kinase inhibitor sorafenib, we generated EVs enriched in specific non-coding RNAs (miR-23b-3p, miR-126-3p, and the long ncRNA GAS5) and investigated their potential impact on the aggressive properties of the BC in vitro and in vivo using zebrafish. Methods: EVs were collected from 4 different BC cell lines (HCC1937, MDA-MB-231, MCF-7, and MDA-MB-453) and characterized by western blotting, transmission electron microscopy and nanoparticle tracking analysis. Levels of encapsulated miR-23b-3p, miR-126-3p, and GAS5 were quantified by ddPCR. The role of the EVs as carriers of ncRNAs in vivo was established by injecting MDA-MB-231 and MDA-MB-453 cells into zebrafish embryos followed by EV-based treatment of the xenografts with EVs rich in miR-23b-3p, miR-126-3p and GAS5. Results: ddPCR analysis revealed elevated levels of miR-23b-3p, miR-126-3p, and GAS5, encapsulated in the EVs released by the aforementioned cell lines, following sorafenib treatment. The use of EVs as carriers of these specific ncRNAs in the treatment of BC cells resulted in a significant increase in the expression levels of the three ncRNAs along with the inhibition of cellular proliferation in vitro. In vivo experiments demonstrated a remarkable reduction of xenograft tumor area, suppression of angiogenesis, and decreased number of micrometastasis in the tails after administration of EVs enriched with these ncRNAs. Conclusions: Our study demonstrated that sorafenib-induced EVs, enriched with specific tumor-suppressor ncRNAs, can effectively inhibit the aggressive BC characteristics in vitro and in vivo. Our findings indicate an alternative way to enrich EVs with specific tumor-suppressor ncRNAs by treating the cells with an anticancer drug and support the development of new potential experimental molecular approaches to target the aggressive properties of cancer cells. [ABSTRACT FROM AUTHOR]

Glioblastoma is one of the most lethal brain diseases in humans. Although recent studies have shown reciprocal interactions between N6-methyladenosine (m6A) modifications and long noncoding RNAs (lncRNAs) in gliomagenesis and malignant progression, the mechanism of m6A-mediated lncRNA translational regulation in glioblastoma remains unclear. Herein, we profiled the transcriptomes, translatomes, and epitranscriptomics of glioma stem cells and differentiated glioma cells to investigate the role of m6A in lncRNA translation comprehensively. We found that lncRNAs with numerous m6A peaks exhibit reduced translation efficiency. Transcript-level expression analysis demonstrates an enrichment of m6A around short open reading frames (sORFs) of translatable lncRNA transcripts. Further comparison analysis of m6A modifications in different RNA regions indicates that m6A peaks downstream of sORFs inhibit lncRNA translation more than those upstream. Observations in glioma-associated lncRNAs H19 , LINC00467 , and GAS5 further confirm the negative effect of m6A methylation on lncRNA translation. Overall, these findings elucidate the dynamic profiles of the m6A methylome and enhance the understanding of the complexity of lncRNA translational regulation. [ABSTRACT FROM AUTHOR]

Abstract: Our work aimed to evaluate and differentiate the role of ten lncRNA genes (GAS5, HAND2-AS1, KCNK15-AS1, MAGI2-AS3, MEG3, SEMA3B-AS1, SNHG6, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in the development and progression of epithelial ovarian cancer (EOC). A representative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation levels of all ten lncRNA genes in tumors compared to normal tissues (p < 0.001). Using RT-qPCR, we showed downregulation and an inverse relationship between methylation and expression levels for ten lncRNAs (rs < −0.5). We further identified lncRNA genes that were specifically hypermethylated in tumors from patients with metastases to lymph nodes (HAND2-AS1), peritoneum (KCNK15-AS1, MEG3, and SEMA3B-AS1), and greater omentum (MEG3, SEMA3B-AS1, and ZNF667-AS1). The same four lncRNA genes involved in peritoneal spread were associated with clinical stage and tumor extent (p < 0.001). Interestingly, we found a reversion from increase to decrease in the hypermethylation level of five metastasis-related lncRNA genes (MEG3, SEMA3B-AS1, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in 59 peritoneal metastases. This reversion may be associated with partial epithelial–mesenchymal transition (EMT) in metastatic cells, as indicated by a decrease in the level of the EMT marker, CDH1 mRNA (p < 0.01). Furthermore, novel mRNA targets and regulated miRNAs were predicted for a number of the studied lncRNAs using the NCBI GEO datasets and analyzed by RT-qPCR and transfection of SKOV3 and OVCAR3 cells. In addition, hypermethylation of SEMA3B-AS1, SSTR5-AS1, and ZNF667-AS1 genes was proposed as a marker for overall survival in patients with EOC. [ABSTRACT FROM AUTHOR]

Introduction: Nuclear factor kappa B (NF-κB) is a key regulator of immune and inflammatory responses. Glucocorticoid drugs (GC) act through the glucocorticoid receptor (GR) as immunosuppressant also in pediatric patients inhibiting NF-κB activity. The long non-coding RNA GAS5 interacts with the GR, influencing GC activity. No data on the role of GAS5 on GR-dependent inhibition of NF-κB activity have been published. Methods: This study investigated the impact of GAS5 on NF-κB activity in HeLa cells overexpressing GAS5, both under basal conditions and during GC treatment. The study used EMSA, RNA-immunoprecipitation (RIP), Western blotting, and bioinformatic analyses to assess NF-κB DNA binding, GAS5-p65 interaction, and NF-κB signaling pathway modulation. Results: GAS5 overexpression increased NF-κB DNA binding activity in untreated cells. RNA-IP confirmed a direct interaction between GAS5 and the NF-κB subunit p65, suggesting a potential regulatory mechanism. GAS5 overexpression led to downregulation of NF-κB target genes, TNF-a, and NR3C1. GC treatment reduced NF-κB DNA binding activity in GAS5-overexpressing cells, indicating a potential synergistic effect. Furthermore, GAS5 overexpression increased IκB levels and reduced p-p65/pan-p65 levels during GC treatment. Discussion: GAS5 appears to modulate NF-κB activity in a complex manner, influencing both basal and GC-induced signaling. The interaction between GAS5, GCs, and NF-κB is multi-faceted, and further research is needed to fully elucidate the underlying mechanisms. These findings suggest that GAS5 could be a potential target for personalized therapy, particularly in pediatric patients with inflammatory conditions. [ABSTRACT FROM AUTHOR]

Metastasis to the lymph nodes is one of the most important factors in the poor prognosis of patients with breast cancer; the five-year survival rate for metastatic breast cancer is less than 30%. DNA methylation occurs in the early stages of the development of cancer and also plays an important role in the development of lymphogenous metastases and can serve as a diagnostic and prognostic marker of breast cancer. The lncRNA genes GAS5, HOTAIR, HOTAIRM1, and SSTR5-AS1, presumably hypermethylated in breast cancer and associated with epithelial-mesenchymal transition and metastasis, were bioinformatically selected. Quantitative methyl-specific PCR showed a statistically significant increase in the methylation level of these lncRNA genes in breast tumors compared to the paired norm. Hypermethylation of the HOTAIRM1 and SSTR5-AS1 genes in breast cancer was identified for the first time. Using statistical analysis, positive correlations were established between methylation levels for the GAS5-HOTAIR and SSTR5-AS1-HOTAIRM1 pairs. The result of co-methylation of GAS5 and HOTAIR in breast cancer is consistent with the bioinformatically predicted (using enrichment analysis and the ncPath database) participation of these lncRNAs in the regulation of common signaling pathways and biological processes. The level of methylation of the lncRNA genes HOTAIRM1 and SSTR5-AS1 is associated with indicators of breast cancer progression (stage of the tumor process, tumor size, presence of metastases in the lymph nodes). A model has been proposed for assessing the risk of developing lymphogenous metastases depending on the level of methylation of the HOTAIRM1 gene. Thus, data were obtained on lncRNAs GAS5, HOTAIR, HOTAIRM1, and SSTR5-AS1 and hypermethylation of their genes as factors in the development and progression of metastatic breast cancer. [ABSTRACT FROM AUTHOR]

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

Among the most deadly malignancies that strike women worldwide, ovarian cancer is still one of the most common. The primary factor affecting a patient's survival is early lesion discovery. Unfortunately, because ovarian cancer is a sneaky illness that usually manifests as nonspecific symptoms only in advanced stages, its early detection and screening are challenging. A lot of research is being conducted on effective methods of diagnosing and treating ovarian cancer. Recently, non-coding RNAs (ncRNAs) have gained great popularity, which are considered to be the main regulators of many cellular processes, especially those occurring in cancer. LncRNAs are also being studied for their therapeutic use in the treatment of ovarian cancer and their use in diagnostics and as indicators of poor prognosis. In this article, we reviewed lncRNAs described in the literature that may play an important role in ovarian cancer. [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]

Long non-coding RNA (LncRNA), with transcripts over 200 nucleotides in length, play critical roles in numerous biological functions and have emerged as significant players in the pathogenesis of osteoarthritis (OA), an inflammatory condition traditionally viewed as a degenerative joint disease. This review comprehensively examines the influence of LncRNA on the inflammatory processes driving OA progression, focusing on their role in regulating gene expression, cellular activities, and inflammatory pathways. Notably, LncRNAs such as MALAT1, H19, and HOTAIR are upregulated in OA and exacerbate the inflammatory milieu by modulating key signaling pathways like NF-κB, TGF-β/SMAD, and Wnt/β-catenin. Conversely, LncRNA like MEG3 and GAS5, which are downregulated in OA, show potential in dampening inflammatory responses and protecting against cartilage degradation by influencing miRNA interactions and cytokine production. By enhancing our understanding of LncRNA' roles in OA inflammation, we can better leverage them as potential biomarkers for the disease and develop innovative therapeutic strategies for OA management. This paper aims to delineate the mechanisms by which LncRNA influence inflammatory responses in OA and propose them as novel targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Breast cancer is a leading cause of cancer-related deaths among women both worldwide and in Poland. Consequently, ensuring equitable access to diagnostic tests for all populations is crucial, alongside the urgent need to develop new, minimally invasive methods for early cancer detection with a particular focus on metastasis. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of cancer metastasis. This review aims to investigate the potential of lncRNAs as novel biomarkers for breast cancer, focusing on their mechanisms, clinical relevance, and therapeutic implications. A comprehensive literature search was conducted using PubMed and Google Scholar databases, targeting publications from 2013 to 2024. Keywords included "lncRNA", "biomarker", "breast cancer", "metastasis", "prognosis", and "diagnosis". A total of 111 articles were selected based on their relevance and quality. Recent studies have identified numerous lncRNAs such as HOTAIR, MALAT1, BANCR, NEAT1, H19, and GAS5 as key regulators of various metastatic processes in breast cancer. They can be both upregulated and downregulated. Clinical studies have shown that abnormal lncRNA expression correlates with poor prognosis, higher metastatic potential, and therapy resistance in breast cancer patients. LncRNAs have significant potential as novel biomarkers for breast cancer metastasis because of their regulatory roles in metastasis-related processes and detectability in body fluids. Further research is essential to validate these findings in larger clinical studies and to develop lncRNA-based diagnostic and therapeutic tools, ultimately improving patient outcomes in breast cancer. [ABSTRACT FROM AUTHOR]

Aims: Hypertensive disorders of pregnancy (HDP) is a unique disease during gestational period, which is detrimental to pregnancy outcome. This study examined the clinical significance of long non-coding RNA GAS5 in gestational hypertension (GH) and preeclampsia (PE), aiming to explore potential biomarkers for the disease detection. Methods: 180 pregnant women with HPD including 90 cases with GH and 90 cases with PE, and another 100 healthy pregnant women were enrolled. Serum GAS5 levels were measured by RT-qPCR method. The diagnostic performance of GAS5 was assessed in GH and PE through plotting receiver operating characteristic (ROC) curve. Logistic regression was applied for the identification of independent factors. Results: Elevated serum GAS5 was identified in GH patients, and its diagnostic performance in discriminating GH cases from healthy people was determined by ROC curve. Serum GAS5 was positively associated with SBP, DBP, LDL-C and CRP values. Cases with PE had an increased serum GAS5 level relative to those with GH. Serum GAS5 was identified to be an independent predictor for PE, and can differentiate PE cases from GH ones. with a good diagnositc performance. Cases with high levels of serum GAS5 had a high risk of poor pregnancy outcomes. Conclusion: Elevated serum GAS5 could serve as an effective diagnostic biomarker in discriminating GH patients from healthy people by first trimester screening. Detection of serum GAS5 level has a certain predictive value for PE. [ABSTRACT FROM AUTHOR]

Background: Exosomes (Exos) are involved in the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) on heart failure (HF). We investigated the molecular mechanisms underlying the involvement of BMSC-Exos in ferroptosis on HF. Methods: A rat model of HF and cellular model of hypoxia were established. BMSC-Exos were injected into model rats or co-cultured with model cells. In model rats, the cardiac function (echocardiography), oxidative stress (commercial kits), pathological damage (HE staining), fibrosis (MASSON staining), iron deposition (Prussian blue staining), and cell apoptosis (TUNEL staining) were examined. Viability (cell counting kit-8; CCK-8), cell cycle (flow cytometry), oxidative stress, and Fe2+ levels were detected in the model cells. GAS5, UL3, YAP, and TAZ expression were detected using qRT-PCR, western blotting, and immunohistochemistry analyses. Results: BMSC-Exos restored cardiac function and inhibited oxidative stress, apoptosis, pathological damage, fibrosis, and iron deposition in myocardial tissues of HF rats. In hypoxic cells, BMSC-Exos increased cell viability, decreased the number of G1 phase cells, decreased Fe2+ levels, and inhibited oxidative stress. Ferrostatin-1 (a ferroptosis inhibitor) exhibited a synergistic effect with BMSC-Exos. Additionally, GAS5 was upregulated in BMSC-Exos, further upregulating its target UL3 and Hippo pathway effectors (YAP and TAZ). The relieving effects of BMSC-Exos on HF or hypoxia-induced injury were enhanced by GAS5 overexpression, but weakened by UL3 silencing or verteporfin (a YAP inhibitor). Conclusions: GAS5-harbouring BMSC-Exos inhibited ferroptosis by regulating the UL3/Hippo pathway, contributing to HF remission in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Background: The lncRNA growth arrest-specific 5 (GAS5) is involved in regulating breast cancer progression. In this study, we aimed to elucidate the function and mechanism of GAS5 in breast cancer. Methods: The expressions of GAS5, fat mass and obesity-associated protein (FTO), insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and Quaking (QKI) were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. The m6A modification level of GAS5 was detected using m6A immunoprecipitation assay (MeRIP). The interaction between IGF2BP2 and GAS5 or QKI was detected using RNA immunoprecipitation assay (RIP) and dual luciferase reporter assay. Cell proliferation was measured using the Cell Counting Kit-8 (CCK-8) assay. The biological functions of the FTO/GAS5/IGF2BP2/QKI axis was assessed using the tumor xenograft assay. Results: LncRNA GAS5 expression decreased in breast cancer and was regulated by FTO-mediated m6A modification in an IGF2BP2-dependent manner, resulting in decreased GAS5 stability and expression. GAS5 recruited IGF2BP2 to target QKI and upregulated QKI expression in breast cancer cells. GAS5 suppressed breast cancer growth via IGF2BP2/QKI, and this inhibitory effect was modulated by FTO both in vitro and in vivo. Conclusions: GAS5 regulated by FTO-mediated m6A modification represses the growth of breast cancer via the IGF2BP2/QKI pathway, suggesting that the FTO/GAS5/IGF2BP2/QKI pathway can be a potential target for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Recently, more and more data have been accumulating indicating the role of long noncoding RNAs (lncRNAs) in the regulation of biological processes in cells, as well as in the mechanisms of cancer development and progression. Aberrant methylation of promoter regions of both protein genes and lncRNA genes can disrupt their expression and functional activity. Using bioinformatics databases, six lncRNA genes (GAS5, HOTAIR, LINC00472, LINC00886, SNHG17, and TUG1) with CpG islands differentially expressed and presumably hypermethylated in tumors of patients with ovarian cancer (OC) were selected. Using a sample of 93 OC samples, real-time methylation specific PCR showed a statistically significant (p < 0.05) increase in the level of methylation in tumors. Moreover, for the genes LINC00472, LINC00886, SNHG17, and TUG1, hypermethylation in OC was detected for the first time. Five genes (except SNHG17) showed a further increase in methylation levels at a more advanced stage, and four genes (except SNHG17 and LINC00886) showed a significant association with metastasis. Using real-time RT-PCR, differential changes in the expression level of the GAS5, HOTAIR, SNHG17, and TUG1 genes and a significant correlation of methylation with expression for the GAS5 gene were shown. Thus, hypermethylation associated with the progression and/or development of OC was detected for six lncRNA genes, which is important for elucidating the epigenetic processes involved in the pathogenesis of OC and can be used as new biomarkers of OC. [ABSTRACT FROM AUTHOR]

Purpose: The main purpose of this paper is to explore the interaction between GAS5 and miR-135b-5p to understand their function in the metastasis, invasion, and proliferation of glioma. This may provide new ideas for the pathogenesis and treatment of glioma. Patients and Methods: Western blotting assays and RT‑qPCR were employed to investigate the expression of related genes in glioma tissues or cell lines. CCK-8 was used to examine the impact of GAS5 on cell viability. Motile activities were adopted by the transwell and wound healing experiments. A double luciferase experiment was performed to elucidate transcriptional regulation. Results: GAS5 showed low expression in glioma cells and tissues, and up-regulation of GAS5 could depress the invasion, proliferation, and metastasis of glioma. GAS5 negatively regulates miR-135b-5p, which can counteract the cellular effects caused by GAS5. APC was the target of miR-135b-5p, and GAS5 can regulate the expression of APC by sponging miR-135b-5p. APC overexpression reversed the effects of miR-135b-5p promotion on glioma cells, while miR-135b-5p has the opposite function. As a downstream target gene of GAS5, miR-135b-5p was negatively regulated by GAS5. The restoration of miR-135b-5p can remarkably reverse the impact of GAS5 on glioma cells. In addition, GAS5 increased the expression of APC in glioma cells by inhibiting miR-135b-5p. Conclusion: GAS5 increased APC expression by restraining miR-135b-5p and partially blocked the progression of glioma, suggesting that it could be an advantageous therapeutic target for glioma intervention. [ABSTRACT FROM AUTHOR]

Considering the effect of SIRT1 on improving myocardial fibrosis and GAS5 inhibiting occurrence and development of myocardial fibrosis at the cellular level, the aim of the present study was to investigate whether LncRNA GAS5 could attenuate cardiac fibrosis through regulating mir-217/SIRT1, and whether the NLRP3 inflammasome activation was involved in this process. Isoprenaline (ISO) was given subcutaneously to the male C57BL/6 mice to induce myocardial fibrosis and the AAV9 vectors were randomly injected into the left ventricle of each mouse to overexpress GAS5. Primary myocardial fibroblasts (MCFs) derived from neonatal C57BL/6 mice and TGF-β1 were used to induce fibrosis. And the GAS5 overexpressed MCFs were treated with mir-217 mimics and mir-217 inhibitor respectively. Then the assays of expression levels of NLRP3, Caspase-1, IL-1β and SIRT1 were conducted. The findings indicated that the overexpression of GAS5 reduced the expression levels of collagen, NLRP3, Capase-1, IL-1β and SIRT1 in ISO treated mice and TGF-β1 treated MCFs. However, this effect was significantly weakened after mir-217 overexpression, but was further enhanced after knockdown of mir-217. mir-217 down-regulates the expression of SIRT1, leading to increased activation of the NLRP3 inflammasome and subsequent pyroptosis. LncRNA GAS5 alleviates cardiac fibrosis induced via regulating mir-217/SIRT1 pathway. [ABSTRACT FROM AUTHOR]

The long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) level was demonstrated as involved in pediatric inflammatory bowel disease (IBD) pathogenesis. Since its antisense transcript GAS5-AS1 has never been investigated in IBD, this study aims to detect whether GAS5-AS1 and GAS5 levels are related to IBD clinical parameters and investigate their correlation in vitro. Twenty-six IBD pediatric patients were enrolled; paired inflamed and non-inflamed intestinal biopsies were collected. We evaluated GAS5 and GAS5-AS1 levels by real-time PCR. The role of GAS5 and GAS5-AS1 was assessed in vitro by transient silencing in THP1-derived macrophages. GAS5-AS1 and GAS5 levels were associated with patients' clinical parameters; GAS5-AS1 expression was downregulated in inflamed tissues and inversely correlated with disease activity. A positive correlation between GAS5-AS1 and GAS5 levels was observed in non-inflamed biopsies. On THP1-derived macrophages, a reduced amount of both GAS5-AS1 and GAS5 was observed; accordingly, matrix metalloproteinase (MMP) 9 was increased. After GAS5-AS1 silencing, a downregulation of GAS5 was found, whereas no effect was detected on GAS5-AS1 after GAS5 silencing. Conclusion: This study provided for the first time new insights into the potential role of GAS5-AS1 in IBD. GAS5-AS1 modulates GAS5 levels in vitro and may serve as a potential IBD diagnostic biomarker. What is Known: • GAS5 is involved in regulating intestinal MMP-2 and MMP-9 in pediatric patients with IBD; • GAS5-AS1 has never been investigated in the context of IBD; • GAS5-AS1 regulates the expression of GAS5, increasing its stability in tissues and in vitro cell models of cancer. What is New: • GAS5-AS1 correlated with GAS5 and IBD clinical parameters; • GAS5-AS1 can modulate GAS5 levels in macrophages; • GAS5-AS1 may serve as potential IBD diagnostic biomarker. [ABSTRACT FROM AUTHOR]

Thousands of lncRNAs have been found in zebrafish embryogenesis and adult tissues, but their identification and organogenesis-related functions have not yet been elucidated. In this study, high-throughput sequencing was performed at three different organogenesis stages of zebrafish embryos that are important for zebrafish muscle development. The three stages were 10 hpf (hours post fertilization) (T1), 24 hpf (T2), and 36 hpf (T3). LncRNA gas5, associated with muscle development, was screened out as the next research target by high-throughput sequencing and qPCR validation. The spatiotemporal expression of lncRNA gas5 in zebrafish embryonic muscle development was studied through qPCR and in situ hybridization, and functional analysis was conducted using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9, CRISPR/Cas9). The results were as follows: (1) A total of 1486 differentially expressed lncRNAs were identified between T2 and T1, among which 843 lncRNAs were upregulated and 643 were downregulated. The comparison with T3 and T2 resulted in 844 differentially expressed lncRNAs, among which 482 lncRNAs were upregulated and 362 lncRNAs were downregulated. A total of 2137 differentially expressed lncRNAs were found between T3 and T1, among which 1148 lncRNAs were upregulated and 989 lncRNAs were downregulated, including lncRNA gas5, which was selected as the target gene. (2) The results of spatiotemporal expression analysis showed that lncRNA gas5 was expressed in almost all detected embryos of different developmental stages (0, 2, 6, 10, 16, 24, 36, 48, 72, 96 hpf) and detected tissues of adult zebrafish. (3) After lncRNA gas5 knockout using CRISPR/Cas9 technology, the expression levels of detected genes related to muscle development and adjacent to lncRNA gas5 were more highly affected in the knockout group compared with the control group, suggesting that lncRNA gas5 may play a role in embryonic muscle development in zebrafish. (4) The results of the expression of the skeletal myogenesis marker myod showed that the expression of myod in myotomes was abnormal, suggesting that skeletal myogenesis was affected after lncRNA gas5 knockout. The results of this study provide an experimental basis for further studies on the role of lncRNA gas5 in the embryonic skeletal muscle development of zebrafish. [ABSTRACT FROM AUTHOR]

This study explored the inhibitory effect of miR-223-3p on the proliferation of brain glioma cells and its potential mechanism in relation to growth arrest-specific transcripts (GAS5). We utilized the StarBase tool to predict the binding of GAS5 to miR-223-3p, further confirming the binding relationship between GAS5 and miR-223-3p through a dual luciferase reporter assay and RNA immunoprecipitation. In vitro cultured U87 brain glial cells were categorized into four groups: the control group, quercetin group, GAS5 inhibition group, and quercetin + si-GAS5 group. We analyzed and compared the impacts of quercetin on GAS5/miR-223-3p and pyroptotic proteins (NLRP3, ASC, caspase-1, GSDMD, and GSDME), as well as the proliferative capacity of U87 cells. StarBase's predictions indicated that GAS5 bound to miR-223-3p. This was corroborated by the dual luciferase reporter assay and RNA immunoprecipitation assay, which demonstrated a direct binding between GAS5 and miR -223-3p. Quercetin was observed to enhance GAS5 expression, inhibit the expression of miR-223-3p and pyroptotic proteins (NLRP3, ASC, caspase-1, GSDMD, and GSDME), and suppress the proliferation and invasion of U87 cells (P < 0.05). Downregulation of GAS5 expression correlated with an increase in the expression of miR-223-3p and pyroptotic proteins (NLRP3, ASC, caspase-1, GSDMD, and GSDME), promoting the proliferation and invasion of RC-4B/C cells (P < 0.05). Quercetin was able to reverse the increase in miR-223-3p expression and pyroptotic proteins (NLRP3, ASC, caspase-1, GSDMD, and GSDME) induced by the downregulation of GAS5, thereby inhibiting the proliferation and invasion of U87 cells (P < 0.05). In conclusion, quercetin might inhibit the proliferation of U87 brain glioma cells by promoting the expression of GAS5, which in turn competitively inhibited miR-223-3p and suppressed the pyroptotic signaling pathway. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30–40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5. [ABSTRACT FROM AUTHOR]

Cheng-Xi Sun,1 Li-Yan Han,2,3 Kai Wang,2,3 Shuai Gao2,3 1Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Institute of Hepatology, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Shuai Gao, Department of Hepatology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Tel +86-531-82169593, Fax +86-531-86927544, Email qilugaoshuai@sdu.edu.cn; gaoshuai361@163.comBackground: Acute-on-chronic hepatitis B liver failure (ACHBLF) is a clinical syndrome with an extremely high mortality. In this study, we aim to evaluate the potential role of serum exosomal long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in ACHBLF and its predictive value for 3-month mortality.Methods: From December 2017 to June 2022, we enrolled 110 patients with ACHBLF and 42 healthy controls (HCs). Exosomes were isolated from the serum of the participants. Serum exosomal lncRNA GAS5 was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The functional role of lncRNA GAS5 on hepatocyte phenotypes was investigated through loss-of-function and gain-of-function assays. Exosomal labeling and cell uptake assay were used to determine the exosomes-mediated transmission of lncRNA GAS5 in hepatocytes in vitro.Results: The serum exosomal lncRNA GAS5 was identified to be an independent predictor for 3-month mortality of ACHBLF. It yielded an area under the receiver operating characteristic curve (AUC) of 0.88, which was significantly higher than MELD score (AUC 0.73; P < 0.01). Further study found that lncRNA GAS5 could inhibit hepatocytes proliferation and increase hepatocytes apoptosis. Exosomes-mediated lncRNA GAS5 transfer promoted hepatocytes injury. The knocked down of lncRNA GAS5 weakened H2O2-induced hepatocytes injury.Conclusion: We revealed that serum exosomal lncRNA GAS5 might promote hepatocytes injury and showed high predictive value for 3-month mortality in ACHBLF.Keywords: acute-on-chronic hepatitis B liver failure, exosomes, long noncoding RNA, growth arrest-specific 5, prognosis

The GAS5 gene encodes a long non-coding RNA (lncRNA) and intron-located small nucleolar RNAs (snoRNAs). Its structure, splice variants, and diverse functions in mammalian cells have been thoroughly investigated. However, there are still no data on a successful knockout of GAS5 in human cells, with most of the loss-of-function experiments utilizing standard techniques to produce knockdowns. By using CRISPR/Cas9 to introduce double-strand breaks in the terminal intronic box C/D snoRNA genes (SNORDs), we created monoclonal cell lines carrying continuous deletions in one of the GAS5 alleles. The levels of GAS5-encoded box C/D snoRNAs and lncRNA GAS5 were assessed, and the formation of the novel splice variants was analyzed. To comprehensively evaluate the influence of specific SNORD mutations, human cell lines with individual mutations in SNORD74 and SNORD81 were obtained. Specific mutations in SNORD74 led to the downregulation of all GAS5-encoded SNORDs and GAS5 lncRNA. Further analysis revealed that SNORD74 contains a specific regulatory element modulating the maturation of the GAS5 precursor transcript. The results demonstrate that the maturation of GAS5 occurs through the m6A-associated pathway in a SNORD-dependent manner, which is a quite intriguing epitranscriptomic mechanism. [ABSTRACT FROM AUTHOR]

Long non-coding (lnc)RNAs are a highly diverse collection of RNAs with a broad spectrum of regulatory mechanisms and functions. Among those, small nucleolar (sno)RNA host genes (SNHGs), which are often highly expressed and include snoRNAs in their introns, are emerging as key players in several biological processes. Both coding and noncoding SNHGs display unique features compared with regular mRNAs and, thus, noncoding SNHGs also have special features compared with other lncRNAs. Some noncoding SNHGs, such as GAS5 , ZFAS1, and SNHG5 , were shown to have important functions in addition to hosting snoRNAs, and some have even evolved functional open reading frames, thus harboring at least three distinct functional features. Mammalian genomes are pervasively transcribed into different noncoding (nc)RNA classes, each one with its own hallmarks and exceptions. Some of them are nested into each other, such as host genes for small nucleolar RNAs (snoRNAs), which were long believed to simply act as molecular containers strictly facilitating snoRNA biogenesis. However, recent findings show that noncoding snoRNA host genes (ncSNHGs) display features different from those of 'regular' long ncRNAs (lncRNAs) and, more importantly, they can exert independent and unrelated functions to those of the encoded snoRNAs. Here, we review and summarize past and recent evidence that ncSNHGs form a defined subclass among the plethora of lncRNAs, and discuss future research that can further elucidate their biological relevance. [ABSTRACT FROM AUTHOR]

This work aimed to investigate the effects of curcumin (Cur) encapsulated in triblock copolymer nanomicelles on lncRNA GAS5 expression and NF-κB signalling pathway in ischemic stroke rats. Using polycaprolactone (PCL), polyethylene (mPEG), polyglutamic acid (PLG), and Cur as raw materials, Cur-PLG-mPEG-PCL nanoparticles were prepared. Its morphology, particle size, and Zeta potential were analyzed. Then seventy-two SD rats were randomly divided into control (Ctrl) group, model group, model + blank nanomicelles (M + BNM) group, model +80 mg/mL Cur (M + C) group, model +40 mg/mL Cur-nanomicelles (M + CNM (40 mg/mL)) group, and model +80 mg/mL Cur nanomicelle (M + CNM (80 mg/mL)) group. The results showed that mean particle size of Cur-PLG-mPEG-PCL was (148.27 ± 27.44) nm, and mean Zeta potential was (−1.97 ± 0.21) mV. The evaluation time of intelligent optimization algorithm based on Single Shot MultiBox Detector (SSD) was significantly shortened, and average EEG power spectrum of ischemic cerebral pawns was significantly lower than that of the control group at θ, α, β, and γ bands for 4h (p < 0.01). These results indicate that the computer intelligent algorithm can be used to evaluate the behaviour of rats, EEG can reflect the changes of cerebral cortical function, and Cur-PLG-mPEG-PCL can improve neurological function and degree of brain injury. [ABSTRACT FROM AUTHOR]

Although, by definition, long noncoding RNAs (lncRNAs) are not translated, they are sometimes associated with ribosomes. In fact, some estimates suggest the existence of more than 50 K lncRNA molecules that could encode for small peptides. We examined the effects of an ethanol and Poly-ADP Ribose Polymerase (PARP) inhibitor (ABT-888) on ribosome-bound lncRNAs. Mice were administered via intraperitoneal injection (i.p.) either normal saline (CTL) or ethanol (EtOH) twice a day for four consecutive days. On the fourth day, a sub-group of mice administered with ethanol also received ABT-888 (EtOH+ABT). Ribosome-bound lncRNAs in CaMKIIα-expressing pyramidal neurons were measured using the Translating Ribosome Affinity Purification (TRAP) technique. Our findings show that EtOH altered the attachment of 107 lncRNA transcripts, while EtOH+ABT altered 60 lncRNAs. Among these 60 lncRNAs, 49 were altered by both conditions, while EtOH+ABT uniquely altered the attachment of 11 lncRNA transcripts that EtOH alone did not affect. To validate these results, we selected eight lncRNAs (Mir124-2hg, 5430416N02Rik, Snhg17, Snhg12, Snhg1, Mir9-3hg, Gas5, and 1110038B12Rik) for qRT-PCR analysis. The current study demonstrates that ethanol-induced changes in lncRNA attachment to ribosomes can be mitigated by the addition of the PARP inhibitor ABT-888. [ABSTRACT FROM AUTHOR]

Retinal endothelial cell activation is a central event in non-infectious posterior uveitis. There is recent interest in long non-coding (lnc)RNA-targeted therapeutics for retinal diseases. We aimed to identify human retinal endothelial cell lncRNAs that might be involved in activation. Eleven candidate lncRNAs were identified: GAS5, KCNQ1OT1, LINC00294, MALAT1, MEG3, MIR155HG, NEAT1, NORAD, OIP5-AS1, SENCR, TUG1. Expression was assessed by RT-PCR in human retinal endothelial cells, at baseline and following activation with interleukin (IL)-1β and tumor necrosis factor (TNF)-α. IL-1β significantly upregulated MEG3 and SENCR at 4 and 24 hours; LINC00294, NORAD, OIP5-AS1 and TUG1 at 24 hours; and MIR155HG at 4, 24 and 48 hours; but downregulated GAS5 at 24 and 48 hours. TNF-α significantly upregulated KCNQ1OT1, LINC00294, MEG3, NORAD and SENCR at 4 hours; SENCR and TUG1 at 24 hours; and MIR155HG at all time points. Future studies involving manipulation of MIR155HG may be warranted to explore potential therapeutic applications for non-infectious posterior uveitis. [ABSTRACT FROM AUTHOR]

Background: To investigate the diagnostic value of serum lncRNA growth arrest-specific transcript 5 (lncRNA GAS5) and microRNA-21 (miR-21) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), and elucidate their roles in the pathogenesis. Methods: A microarray technology was used asses lncRNA GAS5 and miR-21 expression profiles in non-anticoagulant blood from 44 patients including T2DM without DN group (DM), T2DM with DN group (DN), and healthy controls group (N), followed by real-time PCR validation. Logistic regression and receiver operating characteristic (ROC) curves were applied to evaluate the clinical indicators among normal, T2DM, and DN patients. Results: The serum lncRNA GAS5 expression in T2DM and DN patients was significantly down-regulated compared with the N group, while the expression of miR-21 was significantly up-regulated (all P < 0.05). Fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) were negatively correlated with serum lncRNA GAS5, and FBG was independently correlated with serum lncRNA GAS5. Urinary microalbumin, total cholesterol (TC), creatinine (Cr), urea, and systolic blood pressure (SBP) were significantly positively correlated with serum miR-21. Glomerular filtration rate (GFR) and albuminuria (ALB) were negatively correlated with serum miR-21, and ALB was independently correlated with serum miR-21. Serum lncRNA GAS5, miR-21 and lncRNA GAS5/miR-21 showed good diagnostic efficiency as the "diagnostic signature" of T2DM and DN. Conclusion: The lncRNA GAS5/miR-21 diagnostic signature may be a more effective non-invasive biomarker for detecting T2DM. In addition, miR-21 alone may be a more accurate serum biomarker for the early screening of DN patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our previous animal experiments have shown that Rongjin Niantong Fang can affect the decomposition and anabolism of cartilage matrix through long non-coding RNA (LncRNA) growth arrest-specific transcript 5 (GAS5)/miR-21, thereby preventing and treating knee osteoarthritis. Whether LncRNA GAS5/miR-21 can be used as a target for the prevention and treatment of knee osteoarthritis still needs to be verified at the cellular level. OBJECTIVE: To explore the mechanism of Rongjin Niantong Fang in the treatment of knee osteoarthritis at the cellular level. METHODS: (1) Forty 8-week-old SPF male Sprague-Dawley rats were randomly divided into blank serum group, Rongjin Niantong Fang-containing serum group, and glucosamine hydrochloride capsule-containing serum group. 0.9% normal saline, Rongjin Niantong Fang (0.45 g/mL), and glucosamine hydrochloride capsule (0.015 g/mL) were intragastrically given to the rats in the corresponding groups to collect drug containing serum. (2) Cells were treated with interleukin-1β to induce degenerative chondrocyte model. (3) Chondrocytes from the knee joint of Sprague-Dawley rats were isolated and cultured. Passage 2 chondrocytes were obtained and divided into blank group (blank serum), and model group (interleukin-1β+blank serum), treatment group (interleukin1β+Rongjin Niantong Fang-containing serum), and control group (interleukin-1β+glucosamine hydrochloride capsule-containing serum). After 48 hours of intervention, the gene and protein expressions of LncRNA GAS5, miR-21, tissue inhibitor of metalloproteinases 3 (TIMP-3), matrix metalloproteinase (MMP)- 3, MMP-9, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) were detected by real-time PCR and western blot, respectively. (4) Chondrocytes were transfected with LncRNA GAS5 overexpression lentiviral vector. Then, the transfected cells were divided into LncRNA GAS5 empty vector + blank serum group, LncRNA GAS5 empty vector + Rongjin Niantong Fang-containing serum group, LncRNA GAS5 overexpression + blank serum group, and LncRNA GAS5 overexpression + Rongjin Niantong Fang-containing serum group. The gene expressions of LncRNA GAS5, miR-21, TIMP-3, MMP-9, MMP-13, and ADAMTS-5 were detected using real-time PCR. RESULTS AND CONCLUSION: Culture with the serum containing 10% Rongjin Niantong Fang and 15% glucosamine hydrochloride capsule for 48 hours significantly increased the activity of chondrocytes. Compared with the model group, Rongjin Niantong Fang-containing serum and glucosamine hydrochloride capsule-containing serum could inhibit the gene expression of LncRNA GAS5, MMP-3, MMP-9, MMP-13, and ADAMTS-5 (P < 0.05) and promote the gene and protein expression of miR-21 and TIMP-3 (P < 0.05). Compared with the blank group, the gene expression of LncRNA GAS5, MMP-3, MMP-9, MMP-13, and ADAMTS-5 in the LncRNA GAS5 overexpression group increased significantly (P < 0.05), while the gene expression of miR-21 and TIMP-3 decreased significantly (P < 0.05). Compared with the LncRNA GAS5 overexpression+blank serum group, the gene expression of MMP-9, MMP-13, and ADAMTS-5 was significantly decreased in the LncRNA GAS5 overexpression+Rongjin Niantong Fang-containing serum group (P < 0.05), while the gene expression of miR-21 and TIMP-3 were significantly increased (P < 0.05). To conclude, Rongjin Niantong Fang could delay the degradation of cartilage extracellular matrix by promoting TIMP-3 expression and inhibiting the expression of MMP-3, MMP-9, MMP-13 and ADAMTS-5 through regulating LncRNA GAS5/miR-21, thereby preventing and treating knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: This study explores the association between growth arrest-specific 5 (GAS5) rs145204276, nuclear paraspeckle assembly transcript 1 (NEAT1) rs512715, and Maternally Expressed 3 (MEG3) rs4081134 polymorphisms and their impact on susceptibility to papillary thyroid carcinoma (PTC), considering differential expression of long noncoding RNAs (lncRNAs) in PTC. Methods: A case-control study involving 125 papillary thyroid carcinoma (PTC) patients and 125 controls was conducted. Genotyping of polymorphisms was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. Results: No significant association was found between the two groups regarding genotypes and allelic frequencies of GAS-5 145204276 and MEG3 rs4081134 polymorphisms. Genetic models also showed the same results. Regarding NEAT1 rs512715, The PTC group had more GC genotypes and over-dominant models of NEAT1 rs512715 than controls, while controls showed a higher frequency of recessive models. Conclusion: GAS5 rs145204276 and MEG3 rs4081134 polymorphisms showed no significant association with papillary thyroid carcinoma (PTC) risk. In contrast, NEAT1 rs512715 exhibited a significant impact on PTC development. [ABSTRACT FROM AUTHOR]

Low birthweight rats due to fetal undernutrition sustain higher corticosterone levels when exposed to stress. This is due to the upregulated expression of the pituitary-specific Gas5, a long noncoding RNA (lncRNA) that acts as a glucocorticoid receptor decoy and then competitively inhibiting the binding of glucocorticoids to DNA. However, the mechanism of Gas5 lncRNA upregulation remains unclear. Therefore, using the fetal undernourished model, we identified the factors that regulated Gas5 lncRNA expression and examined their effect on subsequent generations. We found that the expression levels of miR-23 was significantly lower in low birth-weight rats compared with controls. The expression of miR-23 was significantly lower and the expression levels of Gas5 lncRNA were significantly higher in the pituitary gland of low birth-weight offspring of the F2 and F3 generations compared with controls. The methyl modulator intervention in lactating F0 maternal rats restored miR-23 and Gas5 lncRNA expressions not only in F1, F2 and F3 offspring. Moreover, the intervention reduced circulating corticosterone levels and gene expressions in the pituitary gland after restraint stress exposure. In conclusion, miR-23-mediated alterations of the stress response are inherited and restored by methyl modulator intervention during lactation. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) patients suffer from severe disability and premature death because of failure in prognosis, diagnosis, and treatment. Although neural mechanisms of bipolar have not been fully discovered, studies have shown long noncoding RNAs (lncRNAs) can play an important role in signaling pathways such as PI3K/AKT pathway. There has been little study on deregulated lncRNAs and the lncRNAs' mode of action in the BD. Hence, we aimed to investigate the expression of PI3K/AKT pathway-related lncRNAs named TUG1, GAS5, and FOXD3-AS1 lncRNAs in the PMBC in 50 bipolar patients and 50 healthy controls. Our results showed that FOXD3-AS1 and GAS5 under-expressed significantly in bipolar patients compared to healthy controls (P = 0.0028 and P < 0.0001 respectively). Moreover, after adjustment, all P values remained significant (q value < 0.0001). According to the ROC curve, AUC (area under the curve), specificity, and sensitivity of these lncRNAs, GAS5 and FOXD3-AS1 might work as BD candidate diagnostic biomarkers. Taken together, the current results highlight that the dysregulation of FOXD3-AS1 and GAS5 may be associated with an increased risk of BD. [ABSTRACT FROM AUTHOR]

Previous studies indicated long non-coding RNAs (lncRNAs) participated in the pathogenesis of atrial fibrillation (AF). However, little is known about the role of lncRNAs in AF-induced electrical remodeling. This study aimed to investigate the regulatory effect of lncRNA GAS5 (GAS5) on the electrical remodeling of neonatal rat cardiomyocytes (NRCMs) induced by rapid pacing (RP). RNA microarray analysis yielded reduced GAS5 level in NRCMs after RP. RT-qPCR, western blot, and immunofluorescence yielded downregulated levels of Nav1.5, Kv4.2, and Cav1.2 after RP, and whole-cell patch-clamp yielded decreased sodium, potassium, and calcium current. Overexpression of GAS5 attenuated electrical remodeling. Bioinformatics tool prediction analysis and dual luciferase reporter assay confirmed a direct negative regulatory effect for miR-27a-3p on lncRNA-GAS5 and HOXa10. Further analysis demonstrated that either miR-27a-3p overexpression or the knockdown of HOXa10 further downregulated Nav1.5, Kv4.2, and Cav1.2 expression. GAS5 overexpression antagonized such effects in Nav1.5 and Kv4.2 but not in Cav1.2. These results indicate that, in RP-treated NRCMs, GAS5 could restore Nav1.5 and Kv4.2 expression via the miR-27a-3p/HOXa10 pathway. However, the mechanism of GAS5 restoring Cav1.2 level remains unclear. Our study suggested that GAS5 regulated cardiac ion channels via the GAS5/miR-27a-3p/HOXa10 pathway and might be a potential therapeutic target for AF. [ABSTRACT FROM AUTHOR]

Introduction: Myocardial hypoxia is an important factor causing myocardial infarction (MI). Interestingly, many unknown factors in the molecular mechanism of MI remain unclear. Our study explored the role of lncRNA growth arrest‐specific 5 (GAS5) in cell injury under hypoxia. Methods: AS5 expression was assessed in MI and human cardiomyocytes under hypoxia through RT‐qPCR assay. Methyl thiazolyl tetrazolium assay, flow cytometry assay, and transwell assay was carried out for cell viability, cell apoptosis, cell migration, and invasion, respectively. The regulatory target of GAS5 was explored through a dual‐luciferase reporter assay. Results: Our findings indicated that the upregulation of GAS5 was related to hypoxia. Downregulation of GAS5 expression could decrease hypoxia‐induced cell apoptosis and increase cell migration and invasion. Moreover, GAS 5 targeted miR‐21, which regulated the phosphatase and tension homology deleted on chromosome ten gene (PTEN) expression. Furthermore, the knockdown of miR‐21 eliminated the effect of GAS5 silencing on cell injury. Conclusion: These results indicated that lncRNA GAS5 silencing decreased cardiomyocyte injury by hypoxia‐induced through regulating miR‐21/PTEN. [ABSTRACT FROM AUTHOR]

Background: Sepsis induces GAS5 expression in the vascular endothelium, but the molecular mechanism is unclear, as is the role of GAS5 in sepsis. Methods and results: We observed that GAS5 expression in the endothelium was significantly upregulated in a sepsis mouse model. ChIP-PCR and EMSA confirmed that the oxidative stress (OS)-activated MiT–TFE transcription factor (MITF, TFE3, and TFEB)-mediated GAS5 transcription. In vitro, GAS5 overexpression attenuated OS and inflammation in endothelial cells (ECs) while maintaining the structural and functional integrity of mitochondria. In vivo, GAS5 reduced tissue ROS levels, maintained vascular barrier function to reduce leakage, and ultimately attenuated sepsis-induced lung injury. Luciferase reporter assays revealed that GAS5 protected MITF from degradation by sponging miR-23, thereby forming a positive feedback loop consisting of MITF, GAS5, and miR-23. Despite the fact that the OS-activated MITF–GAS5–miR-23 loop boosted MITF-mediated p62 transcription, ECs do not need to increase mitophagy to exert mitochondrial quality control since MITF-mediated Nrf2 transcription exists. Compared to mitophagy, MITF-transcribed p62 prefers to facilitate the autophagic degradation of Keap1 through a direct interaction, thereby relieving the inhibition of Nrf2 by Keap1, indicating that MITF can upregulate Nrf2 at both the transcriptional and posttranscriptional levels. Following this, ChIP-PCR demonstrated that Nrf2 can also transcribe MITF, revealing that there is a reciprocal positive regulatory association between MITF and Nrf2. Conclusion: In sepsis, the ROS-activated MITF–GAS5–miR-23 loop integrated the antioxidant and autophagy systems through MITF-mediated transcription of Nrf2 and p62, which dynamically regulate the level and type of autophagy, as well as exert antioxidant and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Background/Aim. Prostate carcinoma (PCa) is second occurring carcinoma that affects the male population. Although PCa incidence rates are high, most cases have a favorable prognosis, with comfortable long-term life quality. The aim of the study was to compare long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) plasma levels between healthy individuals and patients with PCa, and also between PCa patients with different prognostic scores. Methods. The present study included a total of 40 patients with PCa and a control group of 20 healthy individuals. PCa patients were divided into two subgroups (20 patients each) based on the prognostic criteria of the American Joint Committee on Cancer. The patient data were collected and analyzed; lncRNA GAS5 levels were quantified using the real-time polymerase chain reaction method. Statistical analysis was conducted using the IBM SPSS Statistics 26.0 computer program (IBM, USA, 2019). Results. The relative quantification of lncRNA GAS5 expression levels showed downregulation in PCa patients compared to healthy individuals; however, the difference was marginally statistically significant (p = 0.056). With further analysis of the given results, we concluded that the expression level of lncRNA GAS5 was not significantly different in the first patient subgroup and the healthy individuals (p = 0.268). Patients from the second subgroup had significantly lower plasma levels of lncRNA GAS5 than healthy individuals (p = 0.033). The difference in the level of lncRNA GAS5 expression between patients with favorable prognoses (Group 1) and the ones with worse prognostic scores (Group 2) did not indicate statistical significance (p = 0.275). In both Group 1 (p = 0.805) and Group 2 (p = 0.454), the plasma levels of lncRNA GAS5 were not significantly different in comparison to the age (≤ 65 vs. > 65 years). Conclusion. One of the main objectives of PCa research is identifying novel and more efficient biomarkers. Conducted research provides strong evidence about the significance of lncRNAs GAS5 in PCa, as well as the correlation between decreased expression of lncRNA GAS5 and poor prognosis in various tumors. [ABSTRACT FROM AUTHOR]

In recent years, researchers have begun to realize the importance of the role of non-coding RNAs in the treatment of cancer and cardiovascular and neurological diseases. LncRNAs and miRNAs are important non-coding RNAs, which regulate gene expression and activate mRNA translation through binding to diverse target sites. Their involvement in the regulation of protein function and the modulation of physiological and pathological conditions continues to be investigated. Sirtuins, especially Sirt1, have a critical function in regulating a variety of physiological processes such as oxidative stress, inflammation, apoptosis, and autophagy. The lncRNAs/miRNAs/Sirt1 axis may be a novel regulatory mechanism, which is involved in the progression and/or prevention of numerous diseases. This review focuses on recent findings on the crosstalk between non-coding RNAs and Sirt1 in myocardial and cerebral injuries and may provide some insight into the development of novel approaches in the treatment of these disorders. Abbreviation: BMECs, brain microvascular endothelial cells; C2dat1, calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D)-associated transcript 1; EPCs, endothelial progenitor cells; FOXOs, forkhead transcription factors; GAS5, growth arrest-specific 5; HAECs, human aortic endothelial cells; HAND2-AS1, HAND2 Antisense RNA 1; HIF-1α, hypoxia-inducible factor-1α; ILF3-AS1, interleukin enhancer-binding factor 3-antisense RNA 1; KLF3-AS1, KLF3 antisense RNA 1; LncRNA, long noncoding RNA; LUADT1, Lung Adenocarcinoma Associated Transcript 1; MALAT1, Metastasis-associated lung adenocarcinoma transcript 1; miRNA, microRNA; NEAT1, nuclear enriched abundant transcript 1; NF-κB, nuclear factor kappa B; OIP5-AS1, Opa-interacting protein 5-antisense transcript 1; Sirt1-AS, Sirt1 Antisense RNA; SNHG7, small nucleolar RNA host gene 7; SNHG8, small nucleolar RNA host gene 8; SNHG12, small nucleolar RNA host gene 12; SNHG15, small nucleolar RNA host gene 15; STAT3, signal transducers and activators of transcription 3; TUG1, taurine up-regulated gene 1; VSMCs, vascular smooth muscle cells; XIST, X inactive specific transcript; ZFAS1, ZNFX1 Antisense RNA 1. [ABSTRACT FROM AUTHOR]

Asthma is a heterogeneous entity encompassing distinct endotypes and varying phenotypes, characterized by common clinical manifestations, such as shortness of breath, wheezing, and variable airflow obstruction. Two major asthma endotypes based on molecular patterns are described: type 2 endotype (allergic-asthma) and T2 low endotype (obesity-related asthma). Long noncoding RNAs (lncRNAs) are transcripts of more than 200 nucleotides in length, currently involved in many diverse biological functions, such as chromatin remodeling, gene transcription, protein transport, and microRNA processing. Despite the efforts to accurately classify and discriminate all the asthma endotypes and phenotypes, if long noncoding RNAs could play a role as biomarkers in allergic asthmatic and adolescent obesity-related asthma, adolescents remain unknown. To compare expression levels of lncRNAs: HOTAIRM1, OIP5-AS1, MZF1-AS1, and GAS5 from whole blood of Healthy Adolescents (HA), Obese adolescents (O), allergic asthmatic adolescents (AA) and Obesity-related asthma adolescents (OA). We measured and compared expression levels from the whole blood of the groups mentioned above through RT-q-PCR. We found differentially expressed levels of these lncRNAs between the groups of interest. In addition, we found a discriminative value of previously mentioned lncRNAs between studied groups. Finally, we generated an interaction network through bioinformatics. Expression levels of OIP5-AS1, MZF1-AS1, HOTAIRM1, and GAS5 in whole blood from the healthy adolescent population, obese adolescents, allergic asthma adolescents, and obesity-related asthma adolescents are differently expressed. Moreover, these lncRNAs could act as molecular biomarkers that help to discriminate between all studied groups, probably through molecular mechanisms with several genes and miRNAs implicated. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a worldwide disease with rapidly increasing prevalence. This complex disorder caused by interplay between genetic predisposition factors, early developmental elements, diet and inactive lifestyle. Several researches have shown impact of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the pathogenesis of this disorder. Several miRNAs such as miR-126, miR-222-3p, miR-182, let-7b-5p, and miR-1-3p have been down-regulated in different biological sources of patients with T2DM. Some other miRNAs including miR-21, miR-30d, miR-148a-3p, miR-146b and miR-486 have the opposite trends. In addition, a number of lncRNAs such as LY86-AS, HCG27_201, VIM‐AS1, CTBP1‐AS2, CASC2, GAS5, LINC-PINT, and MALAT1 have been altered in the peripheral blood, serum samples or tissues obtained from patients with T2DM. Taken together, both miRNAs and lncRNAs contribute to the development of T2DM and might be applied as markers or therapeutic molecules for this disorder. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of neurodegenerative diseases. It has also been hypothesized that plasma exosomal lncRNAs may be used as Alzheimer's disease (AD) biomarkers. In this systematic review, we compiled all studies on the subject to evaluate the accuracy of lncRNAs in identifying AD cases through meta-analysis. Methods: A PRISMA-compliant systematic search was conducted in PubMed/MEDLINE, EMBASE, and Web of Science databases for English publications till September 2022. We included all observational studies published which investigated the sensitivity and specificity of various lncRNAs in plasma samples of AD diagnosis. Our search strategy included lncRNA and all the related spelling and abbreviation variations combined with the keyword Alzheimer's disease. Methodological quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-II) tool. The meta-analysis was carried out using the area under the Receiver Operator Characteristic (ROC) curves (AUC) and sensitivity and specificity values to assess the accuracy of the identified lncRNAs in AD diagnosis. To account for the predicted heterogeneity of the study, a random-effects model was used. All the statistical analyses and visualizations were conducted using Stata 17.0 software. Results: A total of seven studies (AD patients = 553, healthy controls = 513) were included in the meta-analysis. Three lncRNAs were upregulated (RNA BACE-AS1, RNA NEAT1, RNA GAS5), and one lncRNA (MALAT1) was downregulated in plasma samples of AD patients. RNA 51A and RNA BC200 were reported to have variable expression patterns. A lncRNA (RNA 17A) was not significantly different between AD and control groups. The pooled sensitivity, specificity, and AUC values of lncRNAs in identifying AD were (0.74; 95% CI [0.63, 0.82], I2 = 79.2%), (0.88; 95% CI [0.75, 0.94], I2 = 88.9%), and 0.86; 95% CI [0.82, 0.88], respectively. In addition, the pooled diagnostic odds ratio (DOR) of the five individual lncRNAs in AD diagnosis was 20. Conclusion: lncRNAs had high accuracy in identifying AD and must be seen as a promising diagnostic biomarker of the disease. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a condition that may cause persistent pulmonary damage. The transformation of pericytes into myofibroblasts has been recognized as a key player during IPF progression. This study aimed to investigate the functions of lncRNA growth arrest-specific transcript 5 (GAS5) in myofibroblast transformation during IPF progression. Methods: We created a mouse model of pulmonary fibrosis (PF) via intratracheal administration of bleomycin. Pericytes were challenged with exogenous transforming growth factor-β1 (TGF-β1). To determine the expression of target molecules, we employed quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical and immunofluorescence staining. The pathological changes in the lungs were evaluated via H&E and Masson staining. Furthermore, the subcellular distribution of GAS5 was examined using FISH. Dual-luciferase reporter assay, ChIP, RNA pull-down, and RIP experiments were conducted to determine the molecular interaction. Results: GAS5 expression decreased whereas PDGFRα/β expression increased in the lungs of IPF patients and mice with bleomycin-induced PF. The in vitro overexpression of GAS5 or silencing of PDGFRα/β inhibited the TGF-β1-induced differentiation of pericytes to myofibroblasts, as evidenced by the upregulation of pericyte markers NG2 and desmin as well as downregulation of myofibroblast markers α-SMA and collagen I. Further mechanistic analysis revealed that GAS5 recruited KDM5B to promote H3K4me2/3 demethylation, thereby suppressing PDGFRα/β expression. In addition, KDM5B overexpression inhibited pericyte–myofibroblast transformation and counteracted the promotional effect of GAS5 knockdown on pericyte–myofibroblast transformation. Lung fibrosis in mice was attenuated by GAS5 overexpression but promoted by GAS5 deficiency. Conclusion: GAS5 represses pericyte–myofibroblast transformation by inhibiting PDGFRα/β expression via KDM5B-mediated H3K4me2/3 demethylation in IPF, identifying GAS5 as an intervention target for IPF. [ABSTRACT FROM AUTHOR]

Stroke has become the most common cause of death among residents in China, among which ischemic stroke accounts for the vast majority reaching 70% to 80%. It is of great importance to actively investigate the protective mechanism of cerebral ischemia injury after IS (ischemic stroke). We constructed cerebral ischemia injury models in vivo MACO rat and in vitro (oxygen-glucose deprivation cell model) and set up different interference groups. RT-PCR (reverse transcription PCR) was conducted to detect the expression of lncRNA in neuronal cells, brain tissue, and plasma of different groups, and ELISA (enzyme-linked immunosorbent assay) and western blot were used to detect the expression of the protein in neuronal cells, brain tissue, and plasma of different groups. Cell activity was detected by the CCK-8 assay, while cell apoptosis was examined by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. In the rats' neuronal cells and brain tissue, curcumin can inhibit the expression of lncRNA GAS5 (long noncoding RNA growth arrest-specific 5). In oxygen-glucose-deprived neuronal cells in vitro, curcumin and low-expressed lncRNA GAS5 can enhance cell activity and decline cell apoptosis, but the addition of curcumin and overexpressed lncRNA GAS5 can make this phenomenon disappear. In neuronal cells, plasma, and brain tissue, curcumin and the low-expressed lncRNA GAS5 can inhibit the expression of IL-1β (interleukin 1 beta), TNF-α (tumor necrosis factor alpha), IL-6 (interleukin 6), Sox2 (SRY-box transcription factor 2), Nanog, and Oct4 (octamer-binding transcription factor 4). However, overexpressed lncRNA GAS5 and curcumin made the inhibitory effect disappear. In conclusion, this study demonstrated that curcumin could inhibit the expression of lncRNA GAS5, thereby inhibiting the expression of inflammation-related factors IL-1β, TNF-α, and IL-6, and ultimately achieve the purpose of attenuating cerebral ischemic cell damage. However, curcumin and lncRNA GAS5 may not alleviate cerebral ischemic cell damage by affecting stem cell differentiation. [ABSTRACT FROM AUTHOR]

Introduction: Globally, one of the major causes of cancer related deaths in women is breast cancer. Although metabolic pattern is altered in cancer patients, robust metabolic biomarkers with a potential to improve the screening and disease monitoring are lacking. A complete metabolome profiling of breast cancer patients may lead to the identification of diagnostic/prognostic markers and potential targets. Objectives: The aim of this study was to analyze the metabolic profile in the serum from 43 breast cancer patients and 13 healthy individuals. Materials & methods: We used 1H NMR spectroscopy for the identification and quantification of metabolites. q-RT-PCR was used to examine the relative expression of lncRNAs. Results: Metabolites such as amino acids, lipids, membrane metabolites, lipoproteins, and energy metabolites were observed in the serum from both patients and healthy individuals. Using unsupervised PCA, supervised PLS-DA, supervised OPLS-DA, and random forest classification, we observed that more than 25 metabolites were altered in the breast cancer patients. Metabolites with AUC value > 0.9 were selected for further analysis that revealed significant elevation of lactate, LPR and glycerol, while the level of glucose, succinate, and isobutyrate was reduced in breast cancer patients in comparison to healthy control. The level of these metabolites (except LPR) was altered in advanced-stage breast cancer patients in comparison to early-stage breast cancer patients. The altered metabolites were also associated with over 25 signaling pathways related to metabolism. Further, lncRNAs such as H19, MEG3 and GAS5 were dysregulated in the breast tumor tissue in comparison to normal adjacent tissue. Conclusion: The study provides insights into metabolic alteration in breast cancer patients. It also provides an avenue to examine the association of lncRNAs with metabolic patterns in patients. [ABSTRACT FROM AUTHOR]

Although the imbalance of circulating levels of Thyroid Hormones (THs) affects female fertility in vertebrates, its involvement in the promotion of Premature Ovarian Aging (POA) is debated. Therefore, altered synthesis of THs in both thyroid and ovary can be a trait of POA. We investigated the relationship between abnormal TH signaling, dysthyroidism, and POA in evolutionary distant vertebrates: from zebrafish to humans. Ovarian T3 signaling/metabolism was evaluated by measuring T3 levels, T3 responsive transcript, and protein levels along with transcripts governing T3 availability (deiodinases) and signaling (TH receptors) in distinct models of POA depending on genetic background and environmental exposures (e.g., diets, pesticides). Expression levels of well-known (Amh, Gdf9, and Inhibins) and novel (miR143/145 and Gas5) biomarkers of POA were assessed. Ovarian dysthyroidism was slightly influenced by genetics since very few differences were found between C57BL/6J and FVB/NJ females. However, diets exacerbated it in a strain-dependent manner. Similar findings were observed in zebrafish and mouse models of POA induced by developmental and long-life exposure to low-dose chlorpyrifos (CPF). Lastly, the T3 decrease in follicular fluids from women affected by diminished ovarian reserve, as well as of the transcripts modulating T3 signaling/availability in the cumulus cells, confirmed ovarian dysthyroidism as a common and evolutionary conserved trait of POA. [ABSTRACT FROM AUTHOR]

In this report, changes in the levels of various long non-coding RNAs (lncRNAs) were demonstrated for the first time in fibroblasts derived from patients suffering from 11 types/subtypes of mucopolysaccharidosis (MPS). Some kinds of lncRNA (SNHG5, LINC01705, LINC00856, CYTOR, MEG3, and GAS5) were present at especially elevated levels (an over six-fold change relative to the control cells) in several types of MPS. Some potential target genes for these lncRNAs were identified, and correlations between changed levels of specific lncRNAs and modulations in the abundance of mRNA transcripts of these genes (HNRNPC, FXR1, TP53, TARDBP, and MATR3) were found. Interestingly, the affected genes code for proteins involved in various regulatory processes, especially gene expression control through interactions with DNA or RNA regions. In conclusion, the results presented in this report suggest that changes in the levels of lncRNAs can considerably influence the pathomechanism of MPS through the dysregulation of the expression of certain genes, especially those involved in the control of the activities of other genes. [ABSTRACT FROM AUTHOR]

Background: Tumor protein p63 (TP63) has been proven to play a role as a tumor suppressor in some human cancers, including non-small cell lung cancer (NSCLC). This study aimed to investigate the mechanism of TP63 and analyze the underlying pathway dysregulating TP63 in NSCLC. Methods: RT-qPCR and Western blotting assays were used to determine gene expression in NSCLC cells. The luciferase reporter assay was performed to explore the transcriptional regulation. Flow cytometry was used to analyze the cell cycle and cell apoptosis. Transwell and CCK-8 assays were performed to test cell invasion and cell proliferation, respectively. Results: GAS5 interacted with miR-221-3p, and its expression was significantly reduced in NSCLC. GAS5, as a molecular sponge, upregulated the mRNA and protein levels of TP63 by inhibiting miR-221-3p in NSCLC cells. The upregulation of GAS5 inhibited cell proliferation, apoptosis, and invasion, which was partially reversed by the knockdown of TP63. Interestingly, we found that GAS5-induced TP63 upregulation promoted tumor chemotherapeutic sensitivity to cisplatin therapy in vivo and in vitro. Conclusion: Our results revealed the mechanism by which GAS5 interacts with miR-221-3p to regulate TP63, and targeting GAS5/miR-221-3p/TP63 may be a potential therapeutic strategy for NSCLC cells. Graphical [ABSTRACT FROM AUTHOR]

The long non-coding RNA Growth Arrest-Specific 5 (GAS5) is pivotal in modulating key signaling pathways by functioning as a molecular sponge for microRNAs (miRNAs). GAS5 is notably recognized for its antitumor properties, primarily through its ability to sequester oncogenic miRNAs, thereby influencing critical pathways such as p53, Wnt/β-catenin, and PI3K/Akt, all of which are integral to cell proliferation, apoptosis, and metastasis. The disruption of GAS5–miRNA interactions has been implicated in various malignancies, reinforcing its potential as both a biomarker and a therapeutic target. This paper delves into the intricate signaling cascades affected by GAS5–miRNA interactions and thoroughly investigates the diagnosis and treatment prospects associated with GAS5. Moreover, it addresses both the challenges and opportunities for translational applicability of these findings in clinical environments. The study emphasizes GAS5’s significance within the cancer molecular landscape and posits that precise modulation of GAS5–miRNA interactions could catalyze transformative developments in cancer diagnostics and therapeutic approaches. This comprehensive review not only highlights the critical role of non-coding RNAs in cancer biology but also aims to lay the groundwork for future investigations aimed at harnessing these insights for therapeutic interventions. [ABSTRACT FROM AUTHOR]

The article "Long noncoding RNA GAS5 promotes proliferation, migration, and invasion by regulation of miR-301a in esophageal cancer" has been retracted from Oncology Research due to concerns about the integrity of the data. Issues were raised regarding the presentation of western blots with possibly anomalous protein bands. Despite attempts to address these concerns with the authors, they did not respond, leading to the retraction of the article. The publisher emphasizes the importance of maintaining the reliability and integrity of published content and apologizes for any inconvenience caused by this situation. [Extracted from the article]

• Aberrant expression of long non-coding RNAs is a common phenomenon in cancer • Long non-coding RNAs are often of young phylogenetic age • Young long non-coding RNAs can regulate old protein coding genes • Regulation of protein-coding genes by long non-coding RNAs can promote ultra-stability [ABSTRACT FROM AUTHOR]