Intergenic RNA Research Articles

LincROR promotes tumor growth of colorectal cancer through the miR-145/WNT2B/WNT10A/Wnt/β-catenin regulatory axis.

Colorectal cancer (CRC) is a prevalent form of malignant tumor, and the current clinical treatments are far from satisfactory. Identifying new therapeutic targets is therefore essential for clinical practices. The long intergenic non-protein coding RNA lincROR has been shown to play a significant role in the tumorigenesis of various cancers. However, the molecular mechanism underlying lincROR-mediated CRC tumorigenesis remains unclear. In the present study, we found that knockdown of lincROR significantly inhibited cell viability in vitro, while its overexpression promoted tumor growth in vivo. Mechanistically, lincROR acted as a miRNA sponge for miR-145, thereby elevating the expression of the target genes WNT2B and WNT10A. The overexpression of WNT2B and WNT10A definitely activated the Wnt/β-catenin pathway, thus led to promoting tumorigenesis in CRC. In summary, our findings identified lincROR as a novel activator of the Wnt/β-catenin pathway by serving as a miRNA sponge for miR-145 and facilitating tumorigenesis, which suggests that lincROR may be a potential therapeutic target for CRC patients.

Sequencing CURLY LEAF-associated RNAs in Arabidopsis revealed prevalent intergenic RNAs from the nuclear mitochondrial sequence

Polycomb Group (PcG) proteins play key roles in development by repressing thousands of targets through histone modifications. However, how PcG is recruited to specific targets is poorly understood. In Arabidopsis, certain noncoding RNAs are necessary for recruiting the PcG protein CURLY LEAF (CLF) to its target sites. However, RNAs associated with CLF have not been analyzed on a genomic scale, thus it is unknown whether long noncoding RNA (lncRNA)-mediated PcG recruitment is a widespread mechanism. Here, we systematically searched for CLF-associated RNAs by RNA immunoprecipitation followed by deep sequencing. We identified 1299 genic and 138 intergenic regions that produced CLF-associated mRNAs and putative lncRNAs, respectively. The genes producing CLF-associated RNAs are depleted in PcG targets, carry active chromatin marks, and are highly expressed, suggesting that CLF may have a non-specific or promiscuous RNA-binding affinity, similar to animal PcG proteins. Notably, a significant portion of the CLF-associated lncRNAs is derived from the nuclear mitochondrial sequence, which is extensively marked by H3K27me3. These findings indicate that while CLF-RNA interactions are widespread, they may not always correlate with PcG target sites, highlighting the complexity of PcG recruitment mechanisms in Arabidopsis.

LncRNA HOTAIR and Cardiovascular diseases.

Cardiovascular diseases (CVDs) a major contributor to global mortality rates, with a steadily rising prevalence observed across the world. Understanding the molecular mechanisms that underlie the signaling pathways implicated in the pathogenesis of CVDs represents a salient and advantageous avenue toward the development of precision and targeted therapeutics. A recent development in CVDs research is the discovery of long non-coding RNAs (lncRNAs), which are now understood to have crucial roles in the onset and development of several pathophysiological processes. The distinct expression patterns exhibited by lncRNAs in various CVDs contexts, present a significant opportunity for their utilization as both biomarkers and targets for therapeutic intervention. Among the various identified lncRNAs, HOX antisense intergenic RNA (HOTAIR) functions as signaling molecules that are significantly implicated in the pathogenesis of cardiovascular disorders in response to risk factors. HOTAIR has been observed to circulate within the bloodstream and possesses an integral epigenetic regulatory function in the transcriptional pathways of many diseases. Recent studies have suggested that HOTAIR offers promise as a biomarker for the detection and treatment of CVDs. The investigation on HOTAIR's role in CVDs, however, is still in its early phases. The goal of the current study is to give a thorough overview of recent developments in the field of analyzing the molecular mechanism of HOTAIR in controlling the pathophysiological processes of CVDs as well as its possible therapeutic uses.

LINC00665 aggravates the malignant phenotypes in chondrosarcoma cells through miR-665/FGF9 pathway

Long non-coding RNAs (lncRNAs) have been demonstrated to participate in a variety of physiological and pathological processes, including tumor initiation and development. Nevertheless, few of them have been investigated in chondrosarcoma. Here, we were intended to unveil the role of long intergenic non-protein coding RNA 665 (LINC00665) in chondrosarcoma. RT-qPCR was adopted for gene expression detection. The biological processes in chondrosarcoma cells were detected by CCK-8, EdU, TUNEL, Transwell and wound healing assays. The relationships between genes in chondrosarcoma cells were evaluated by a series of mechanism experiments including RIP, luciferase reporter assays and so on.LINC00665 expressed at a high level in chondrosarcoma cell lines. LINC00665 interference suppressed cell proliferation, migration and invasion in chondrosarcoma. Besides, LINC00665 interacted with microRNA-665 (miR-665), which was then verified to be down-regulated in chondrosarcoma cells. Additionally, LINC00665 and miR-665 were mutually inhibited by each other in chondrosarcoma cells. Importantly, LINC00665 stimulated fibroblast growth factor 9 (FGF9) expression in chondrosarcoma cells via sponging miR-665. Furthermore, FGF9 participated in the regulation of LINC00665-promoted chondrosarcoma development. ConclusionLINC00665 facilitates chondrosarcoma progression via miR-665/FGF9 axis, which might indicate a new path for the treatment of chondrosarcoma.

Clinical relevance of long non-coding RNA in acute myeloid leukemia: A systematic review with meta-analysis

BackgroundLong noncoding RNAs (lncRNAs) may function as prognostic biomarkers in acute myeloid leukaemia (AML). However, it is still unknown exactly how significant lncRNAs are for the prognosis of AML. With a focus on their prognostic and therapeutic potential, the study aimed to provide a comprehensive review of the literature regarding the role of lncRNAs in AML. MethodPub Med, The Cochrane Library, Embase, Science Direct, Web of science, Scopus, and Google scholar were searched until November, 2023. Original publications of any type exploring the prognostic and therapeutic potential of lncRNAs in AML patients were included. Heterogeneity and publication bias were examined using the I2 test and a funnel plot, respectively. To quantify the relationship between various lncRNA expression in AML patient survival, odds ratios (ORs) or hazards ratios (HRs) with 95 % confidence intervals (CIs) were pooled. Quality of studies was assessed using the Critical Appraisal Checklists for Studies created by the Joanna Briggs Institute (JBI). ResultsTwenty-seven studies including 5665 subjects were selected for the final analysis. In patients with AML, abnormal lncRNA expression has been associated with significant worse overall survival (pooled HR = 2.05, 95 % CI = 1.79–2.30, P <0.001), shorter disease-free survival (pooled HR = 2.17, 95 % CI = 1.13–3.22, P< 0.001), and lower complete remission rate (pooled HR = 0.27, 95 % CI = 0.11–0.43, P< 0.001). Poor prognoses have been attributed to increased expression of HOX transcript antisense intergenic RNA (HOTAIR), Promoter Of CDKN1A Antisense DNA Damage Activated RNA (PANDAR), Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1), RP11–222K16.2, Taurine Upregulated Gene 1 (TUG1), Small Nucleolar RNA Host Gene 5 (SNHG5), Growth Arrest Specific 5 (GAS5), and H19 and decreased expression of IGF1R Antisense Imprinted Non-Protein Coding RNA (IRAIN). ConclusionThe prognoses of AML patients are significantly associated with abnormally expressed lncRNAs, which may be used as prognostic indicators for predicting the patient outcomes.

LINC01503 promotes the cell proliferation, migration and invasion of triple-negative breast cancer as a ceRNA to elevate SPNS2 expression by sponging miR-335–5p

ObjectiveTriple-negative breast cancer (TNBC) is a common cancer with high aggressiveness and high mortality in women. Recently, a plenty of studies have indicated that long non-coding RNAs (lncRNAs) exert the crucial function in human cancers, TNBC is included. The carcinogenicity of lncRNA long intergenic non-protein coding RNA 1503 (LINC01503) has been confirmed in several cancers, nevertheless, its function in TNBC still unclear. Therefore, our study aimed to reveal the underlying mechanism of LINC01503 in TNBC. MethodsIn our study, RT-qPCR was performed to detect the expression of LINC01503 in TNBC cells. The proliferative, invasive, migratory and apoptotic abilities of TNBC cells were detected by functional assay such as CCK-8, clone formation, EdU staining, transwell, and flow cytometry. RIP, RNA pull down, and luciferase assay revealed interactions between LINC01503, miR-335–5p, and sphingolipid transporter protein 2 (SPNS2). Finally, rescue experiments were performed to validate the previous results. ResultsLINC01503 expression was singularly high in TNBC cells. LINC01503 knockdown could restrain cell proliferation, invasion and migration, but accelerated cell apoptosis in TNBC. What’s more, miR-335–5p could be sponged by LINC01503 in TNBC. We also found that overexpressed miR-335–5p could inhibit cell proliferation, migration and invasion and facilitates cell apoptosis. Moreover, SPNS2 was the target gene of miR-335–5p and it functioned as an oncogene in TNBC cells. Finally, we found that overexpressed SPNS2 or inhibited miR-335–5p could reverse the suppressive function of silencing LINC01503 on TNBC progression. ConclusionLINC01503 could facilitate cell proliferation, migration and invasion of TNBC by sponging miR-335–5p to elevate SPNS2 expression.

Identification and Functional Analysis of Novel Long Intergenic RNA in Chicken Macrophages Infected with Avian Pathogenic Escherichia coli.

Avian pathogenic E. coli (APEC), a widespread bacterium, results in serious economic losses to the poultry industry annually, and it poses a threat to human health due to the contaminated retail poultry meat and eggs. Recently, it has been demonstrated that long non-coding RNAs played important roles in regulating gene expression and the animal immune response. This study aimed to systematically explore the function of the novel long intergenic non-coding transcript, lincRNA-73240, upon APEC infection. A bioinformatics analysis indicated that lincRNA-73240 had no coding ability and a relative stable secondary structure with multiple hairpin rings. Moreover, the RT-qPCR results showed that lincRNA-73240 was highly expressed in lungs, heart, liver, spleen, cecum tonsils, thymus, ileum, bursa of Fabricius, harderian gland, and muscles in comparison to the cerebrum. Additionally, overexpression of lincRNA-73240 can promote the expression levels of inflammation, apoptosis, autophagy, and oxidative stress-related genes, as well as the production of reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO) upon APEC infection, which lead to cellular injury and apoptosis. These findings collectively establish a foundation for the study of the biological function of chicken lincRNA-73240 and provide a theoretical basis for further research on the molecular mechanisms of the chicken immune response.

Linc01116 Silencing Inhibits the Proliferation and Invasion, Promotes Apoptosis of Chordoma Cells via Regulating the Expression of Mir-9-5p/PKG1.

Long intergenic non-protein coding RNA 1116 (LINC01116) plays a carcinogenic role in a variety of cancers. The study aims to investigate the roles of LINC01116 and hsa-miR-9-5p (miR-9-5p) and fathom their interaction in chordoma. The predicted binding sites between miR-9-5p with LINC01116 and phosphoglycerate kinase 1 (PGK1) by starBase were confirmed through dual-luciferase reporter assay. The behaviors of chordoma cells undergoing transfection with siLINC01116 or miR-9-5p inhibitor were determined by Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and flow cytometry assays. The glucose consumption, lactate production, and adenosine triphosphate (ATP) production of chordoma cells were examined with specific kits. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to determine relevant gene expressions in chordoma cells. Silencing of LINC01116 facilitated the apoptosis and expressions of Bcl-2- associated X (Bax), cleaved caspase-3 (C caspase-3) and miR-9-5p while repressing the cell cycle, viability, proliferation, invasion, glucose consumption, lactate production, ATP production, and expressions of PGK1 and Bcl-2. Meanwhile, LINC01116 sponged miR-9-5p, which could target PGK1. Moreover, the miR-9-5p inhibitor acted contrarily and reversed the role of siLINC01116 in chordoma cells. Besides, LINC01116 downregulation facilitated apoptosis and attenuated the proliferation and invasion of chordoma cells as well as PGK1 expression by upregulating miR-9-5p expression. LINC01116/miR-9-5p plays a regulatory role in the progression of chordoma cells and is a potential biomarker for chordoma.

LINC00963 Represses Osteogenic Differentiation of hBMSCs via the miR-10b-5p/RAP2A/AKT Axis.

Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is important for human bone formation. Long non-coding RNAs (lncRNAs) are critical regulators in osteogenic differentiation. This study aimed to explore the function and mechanisms of long intergenic non-protein coding RNA 963 (LINC00963) in affecting osteogenesis. Cell differentiation was assessed by alkaline phosphatase (ALP) activity detection and ALP staining assay. Meanwhile, levels of osteogenic marker genes, including RUNX family transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN), were detected by RT-qPCR and western blot. Cell proliferation and apoptosis were measured using CCK-8 assay and flow cytometry analysis. RNA immunoprecipitation (RIP), RNA pull-down and luciferase reporter assays were used to investigate the interaction between genes. LINC00963 expression was down-regulated in hBMSCs treated with osteogenic induction. LINC00963 overexpression inhibited hBMSCs differentiation, proliferation, and elevated apoptosis. LINC00963 acted as a competing endogenous RNA (ceRNA) to interact with miR-10b-5p and thereby regulated the expression level of Ras-related protein Rap-2a (RAP2A). LINC00963 regulated RAP2A to inhibit the level of phosphorylated AKT (p-AKT). LINC00963 inhibited hBMSCs differentiation, proliferation, and elevated apoptosis via the miR-10b-5p/RAP2A/AKT signaling, which might help improve the treatment of osteoporosis.

The lncRNA LINC01605 promotes the progression of pancreatic ductal adenocarcinoma by activating the mTOR signaling pathway

BackgroundThis study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC).MethodsLINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo.ResultsLINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo.ConclusionsOur results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.

LncRNA HOTAIR: A Novel Biomarker for the Diagnosis of Asymptomatic Carotid Artery Stenosis and Prediction of the Onset of Cerebral Ischemic Events

BackgroundCarotid artery stenosis (CAS) is a major cause of cerebral ischemic events (CIE). The purpose of the research was to reveal the diagnostic accuracy of long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) in asymptomatic carotid artery stenosis (ACAS) patients and its predictive significance in CIE incidence.Methods88 patients with ACAS and 80 controls were included. Blood samples were collected and serum HOTAIR levels were detected by qRT-PCR. Logistic regression examined factors associated with the degree of carotid stenosis. The receiver operating characteristic (ROC) curve assessed the diagnostic accuracy of HOTAIR in identifying patients with ACAS. Predictive value of serum HOTAIR levels for the occurrence of CIE was assessed by Kaplan–Meier curves and Cox regression.ResultsSerum HOTAIR was markedly lower in ACAS patients than in controls (P < 0.001). Logistic regressions confirmed that HOTAIR levels correlated with severe carotid artery stenosis (OR = 0.289, 95% CI = 0.107–0.786, P = 0.015). ROC’s AUC was 0.925, indicating high sensitivity and specificity in differentiating between the controls and patients with ACAS. Furthermore, CIE-positive patients had lower HOTAIR levels than CIE-negative, and the degree of carotid stenosis (HR = 4.566, 95% CI = 1.206–17.292, P = 0.025) and HOTAIR levels (HR = 0.244, 95% CI = 0.072–0.824, P = 0.023) were independent risk factors for the development of CIE. Patients with lower HOTAIR were more susceptible to CIE (log-rank P = 0.001).ConclusionsSerum HOTAIR was reduced in patients with ACAS and may be a non-invasive diagnostic biomarker for ACAS and predicts the development of CIE.

Long intergenic non-protein coding RNA 1436 accelerates cell proliferation, migration and adhesion properties of the MUM-2B cell line via microRNA-513a-5p/CUG Triplet repeat-binding protein 1 axis to activate the phosphatidylinositol 3-kinase/Akt signaling pathway

Long intergenic non-protein coding RNA 1436 accelerates cell proliferation, migration and adhesion properties of the MUM-2B cell line via microRNA-513a-5p/CUG Triplet repeat-binding protein 1 axis to activate the phosphatidylinositol 3-kinase/Akt signaling pathway

Long non-coding intergenic RNA, LINC00273 induces cancer metastasis and stemness via miRNA sponging in triple negative breast cancer

LncRNAs and miRNAs, being the master regulators of gene expression, are crucial functional mediators in cancer. Our study unveils the critical regulatory role of the metastatic long non-coding RNA LINC00273 as the master regulator of oncogenes involved in cancer metastasis, stemness, and chemoresistance via its miRNA sponging mechanism. M2 (a salt of bis-Schiff base) mediated G quadruplex (G4) stabilization at the LINC00273 gene promoter remarkably inhibits LINC00273 transcription. Therefore, low-level LINC00273 transcripts are unable to efficiently sponge the miRNAs, which subsequently become available to bind and downregulate their target oncogenes. We have observed significantly different global transcriptomic scenarios in LINC00273 upregulated and downregulated circumstances in MDA-MB-231 triple-negative breast cancer model. Additionally, we have found the G4 sequence in the LINC00273 RNA to play a critical role in miRNA sequestration. miRNAs (miR-6789-5p, miR200b, miR-125b-5p, miR-4268, miR3978) have base pairing complementarity within the G4 region of LINC00273 RNA and the 3′-UTR (untranslated region) of MAPK12, TGF-β1, and SIX-1 transcripts. We have reported TGF-β1, SIX-1, and MAPK12 to be the direct downstream targets of LINC00273. The correlation between abnormal expression of lncRNA LINC00273 and TNBC aggressiveness strongly evidenced in our study shall accelerate the development of lncRNA-based anti-metastatic therapeutics.

The role of HOTAIR in the modulation of resistance to anticancer therapy.

Leading anti-tumour therapeutic strategies typically involve surgery and radiotherapy for locally advanced (non-metastatic) cancers, while hormone therapy, chemotherapy, and molecular targeted therapy are the current treatment options for metastatic cancer. Despite the initially high sensitivity rate to anticancer therapies, a large number of patients develop resistance, leading to a poor prognosis. The mechanisms related to drug resistance are highly complex, and long non-coding RNAs appear to play a crucial role in these processes. Among these, the lncRNA homeobox transcript antisense intergenic RNA (HOTAIR), widely implicated in cancer initiation and progression, likewise plays a significant role in anticancer drug resistance. It can modulate cell activities such as proliferation, apoptosis, hypoxia, autophagy, as well as epithelial-mesenchymal transition, thereby contributing to the development of resistant tumour cells. In this manuscript, we describe different mechanisms of antitumor drug resistance in which HOTAIR is involved and suggest its potential as a therapeutic predictive biomarker for the management of cancer patients.

Abstract 2014: Long Non-coding RNA LINC-PINT Regulates Smooth Muscle Cell Plasticity In Developing Abdominal Aortic Aneurysms

Background: Long noncoding RNAs (lncRNAs) play pivotal roles as molecular regulators in diverse vascular biological processes and diseases. This study utilized multi-transcriptomic profiling to investigate the contribution of lncRNAs in Abdominal Aortic Aneurysm (AAA) disease. Materials &amp; Methods: Utilizing bulk and single-cell RNA sequencing, we identified lncRNA long intergenic non-protein coding RNA, p53 induced transcript (LINC-PINT) as a significantly deregulated transcript in AAA compared to non-dilated aortas. Deconvolution of single-cell and bulk RNA-sequencing via the BayesPrism tool identified plasticity of smooth muscle cells (SMCs) as the predominant shifted condition between dilated vs. non-dilated aortas. Hybridization-based RNA in situ sequencing (HybRISS) confirmed the presence of LINC-PINT in de-differentiating SMCs. Results: Experimental knock-down of LINC-PINT , using site-specific antisense oligonucleotides (LNA-GapmeRs) markedly decreased proliferation rates of cultured human aortic smooth muscle cells (AoSMCs), but also increased their apoptosis, whereas overexpression of LINC-PINT had the opposite effect. Transcriptomic profiling of LINC-PINT -silenced AoSMCs indicated down-regulation of contractility markers, accompanied by an increase of inflammation and extracellular matrix (ECM) degradation. In line with this, LINC-PINT knock-down abolished the transforming growth factor beta (TGF-β)- induced AoSMCs polarization towards a contractile phenotype. Notably, RNA immunoprecipitation (RIP) demonstrated an interaction between LINC-PINT and p65, inhibiting its translocation to the promoter region of inflammatory genes. LINC-PINT knock-down increased p65 binding to its coactivator p50, which was confirmed by Co-immunoprecipitation (CO-IP). Combined in silico prediction and luciferase reporter assays further revealed that LINC-PINT expression was controlled by the ZNF93 and ZNF263 transcription factors. Conclusion: We provide evidence of LINC-PINT being a novel regulator influencing SMC dynamics and fate decisions of central importance to AAA pathophysiology. Currently ongoing in vivo studies in Lncpint -deficient mice explore its relevance in experimental AAA development.

Effect of prednisolone in a kindling model of epileptic seizures in rats on cytokine and intestinal microbiota diversity

Epilepsy is a neurological disease characterized by spontaneous and recurrent seizures. Epileptic seizures can be initiated and facilitated by inflammatory mechanisms. As the dysregulation of the immune system would be involved in epileptogenesis, it is suggested that anti-inflammatory medications could impact epileptic seizures. These medications could potentially have a side effect by altering the structure and composition of the intestinal microbiota. These changes can disrupt microbial homeostasis, leading to dysbiosis and potentially exacerbating intestinal inflammation. We hypothesize that prednisolone may affect the development of epileptic seizures, potentially influencing the diversity of the intestinal microbiota and the regulation of pro-inflammatory cytokines in intestinal tissue. This study aimed to evaluate the effects of prednisolone treatment on epileptic seizures and investigate the effect of this drug on the bacterial diversity of the intestinal microbiota and markers of inflammatory processes in intestinal tissue. We used Male Wistar rat littermates (n = 31, 90-day-old) divided into four groups: positive control treated with 2 mg/kg of diazepam (n = 6), negative control treated with 0.9 g% sodium chloride (n = 6), and the remaining two groups were subjected to treatment with prednisolone, with one receiving 1 mg/kg (n = 9) and the other 5 mg/kg (n = 10). All administrations were performed intraperitoneally (i.p.) over 14 days. To induce the chronic model of epileptic seizures, we administered pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. Seizure latency (n = 6 – 10) and TNF-α and IL-1β concentrations from intestinal samples were measured by ELISA (n = 6 per group), and intestinal microbiota was evaluated with intergenic ribosomal RNA (rRNA) spacer (RISA) analysis (n = 6 per group). The prednisolone treatment demonstrated an increase in the latency time of epileptic seizures and TNF-α and IL-1β concentrations compared to controls. There was no statistically significant difference in intestinal microbiota diversity between the different treatments. However, there was a strong positive correlation between microbial diversity and TNF-α and IL-1β concentrations. The administration of prednisolone yields comparable results to diazepam on increasing latency between seizures, exhibiting promise for its use in clinical studies. Although there were no changes in intestinal microbial diversity, the increase in the TNF-α and IL-1β cytokines in intestinal tissue may be linked to immune system signaling pathways involving the intestinal microbiota. Additional research is necessary to unravel the intricacies of these pathways and to understand their implications for clinical practice.

The Effect of Melatonin on the Expression of H19, MALAT, HOTAIR, THRIL, and NOS Activity in Leishmania major-Infected Macrophages

Background: Leishmania spp. protozoa cause leishmaniasis by infecting macrophages. Long non-coding RNAs (lncRNAs), such as H19, Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT), HOX Antisense Intergenic RNA (HOTAIR), and TNF and HNRNPL Related Immuno-regulatory lncRNA (THRIL), play a role in macrophage polarization and gene regulation. Additionally, leukocytes can synthesize and respond to melatonin, yet the regulatory role of melatonin in Leishmania major-infected macrophages is not well understood. Objectives: This study aimed to assess the impact of melatonin on the expression of lncRNAs like H19, MALAT, HOTAIR, and THRIL, as well as on nitric oxide synthase (NOS) activity in L. major-infected macrophages. Methods: Leishmania major promastigotes and U937 cell lines were cultured. Macrophages were infected with the promastigotes and subsequently treated with melatonin at concentrations of 3, 10, 30, and 100 nM for durations of 4, 24, and 48 hours. The expression levels of the lncRNAs and NOS activity were measured using quantitative Polymerase Chain Reaction (q-PCR) and spectrophotometry, respectively. Results: Melatonin treatment (100 nM) significantly increased the expression of H19 compared to the control after 48 hours (P = 0.002). There was also a significant upregulation of MALAT and HOTAIR in macrophages treated with 3 nM melatonin compared to controls after 48 hours (P = 0.02 and P = 0.003, respectively). Additionally, THRIL expression significantly increased in the melatonin group (10 nM) compared to the control after 4 hours of treatment (P = 0.003). An increase in NOS activity was observed in the melatonin group (100 nM) compared to the control at 4 hours, 24 hours, and 48 hours (P = 0.034, P = 0.011, and P = 0.014, respectively). Conclusions: The findings suggest that melatonin may enhance the expression of H19, THRIL, MALAT, and HOTAIR, as well as NOS activity in macrophages infected with L. major. The upregulation of these lncRNAs by melatonin could potentially improve the macrophages' ability to combat L. major infection.

Role of Long Intergenic Nonprotein-Coding RNA 00511 in Nod-Like Receptor Protein Pyrin Domain 3-Induced Chondrocyte Pyroptosis via the MicroRNA-9-5p/FUT1 Axis.

This study aimed to determine the function of LINC00511 in Nod-Like Receptor Pyrin Domain 3 inflammasome-mediated chondrocyte pyroptosis via the regulation of miR-9-5p and FUT 1. Chondrocyte inflammatory injury was induced by treating chondrocytes with LPS. Afterwards, the levels of IL-1β and IL-18, the expression of NLRP3, ASC, Caspase-1, and GSDMD, cell viability, and LDH activity in chondrocytes were assessed. LINC00511 expression in LPS-treated chondrocytes was detected, and LINC00511 was subsequently silenced to analyse its role in chondrocyte pyroptosis. The subcellular localization of LINC00511 was predicted and verified. Furthermore, the binding relationships between LINC00511 and miR-9-5p and between miR-9-5p and FUT1 were validated. LINC00511 regulated NLRP3 inflammasome-mediated chondrocyte pyroptosis through the miR-9-5p/FUT1 axis. LPS-treated ATDC5 cells exhibited elevated levels of inflammatory injury; increased levels of NLRP3, ASC, Caspase-1, and GSDMD; reduced cell viability; increased LDH activity; and increased LINC00511 expression, while LINC00511 silencing inhibited the NLRP3 inflammasome to restrict LPS-induced chondrocyte pyroptosis. Next, LINC00511 sponged miR-9-5p, which targeted FUT1. Silencing LINC00511 suppressed FUT1 by upregulating miR-9-5p. Additionally, downregulation of miR-9-5p or overexpression of FUT1 neutralized the suppressive effect of LINC00511 knockdown on LPS-induced chondrocyte pyroptosis. Silencing LINC00511 inhibited the NLRP3 inflammasome to quench Caspase-1-dependent chondrocyte pyroptosis in OA by promoting miR-9-5p and downregulating FUT1.

Role of the lncRNA HOX antisense intergenic RNA myeloid 1 in Cancer: A Review

Role of the lncRNA HOX antisense intergenic RNA myeloid 1 in Cancer: A Review

Linc00958 Promotes Lung Cancer Proliferation and Migration Through Regulating microRNA-490-3p

This study aimed to investigate the role of long intergenic non-protein coding RNA 00958 (Linc00958) in lung cancer (LCa) progression and its underlying mechanism. The study assessed Linc00958 expression in LCa tissues and adjacent tissues using qRT-PCR, and its impact on patient prognosis was analyzed through Kaplan-Meier survival analysis. Additionally, Linc00958 expression in LCa and normal lung cell lines was examined in vitro. Functional assays, including CCK-8, EdU, and transwell assays, were conducted to evaluate the effects of Linc00958 knockdown on LCa cells. To uncover the molecular mechanism, a dual-luciferase reporter assay was used to confirm the binding relationship between Linc00958 and microRNA-490-3p, a downstream gene. Co-transfection experiments were performed to elucidate microRNA-490-3p’s role in Linc00958’s impact on LCa cell functions. The results showed that Linc00958 was overexpressed in LCa tissues and cells, and high Linc00958 expression correlated with reduced patient survival. in vitro experiments revealed that Linc00958 promoted tumor proliferation and migration in LCa cells. Both computational predictions and dual-luciferase reporter assays demonstrated binding sites between microRNA-490-3p and Linc00958. Co-transfection experiments confirmed that Linc00958 facilitated LCa cell proliferation and migration through modulating microRNA-490-3p expression. In summary, Linc00958 promotes LCa cell proliferation and migration by regulating microRNA-490-3p.