Role Of lncRNAs Research Articles

Transcriptomic analysis reveals role of lncRNA LOC100257036 to regulate AGAMOUS during cluster compactness of Vitis vinifera cv. sistan yaghooti.

Yaghooti grape, as the earliest grape variety in Iran, is considered as more resistant to heat, drought, and salinity than other cultivars. Cluster compactness is regarded as an inappropriate feature for the productivity of Yaghooti grape as a critical commercial and nutritional product. In plants, lncRNAs play a critical role in regulating biological processes related to growth and development. However, the potential role of lncRNAs was not assessed in cluster compactness. Totally, 1549 lncRNAs were identified by RNA-Seq data analysis in three steps of cluster formation, berry formation, and final cluster size after a thorough screening process. In addition, 229 lncRNAs were differentially expressed in the cluster development steps. Based on the functional analysis, lncRNAs are related to AG and MYB, bHLH, LBD, NAC, and WRKY TFs. Further, the target genes enrichment analysis revealed a relationship between lncRNAs with grape growth and development, as well as resistance to abiotic stresses such as heat and drought, plant defense against pathogens, and early grapes ripening. The study identified four lncRNAs as precursors of miRNAs, predicting that 112 other lncRNAs could potentially be targeted by 166 miRNAs. The results provide new insights into the regulatory functions of lncRNAs in Yaghooti grape to improve overall understanding of the molecular mechanisms related to grape compactness.

Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells

Abstract Objective Dysregulation of chondrogenic differentiation is associated with osteoarthritis (OA). The myokine irisin is beneficial in OA treatment; yet, the underlying mechanism is not fully understood. Long noncoding RNAs (lncRNAs) act as important regulators of chondrocyte differentiation. This study was conducted to address the role of lncRNAs in mediating irisin-induced chondrocyte differentiation. Methods We investigated the irisin-regulated lncRNA profile change in human mesenchymal stem cells (MSCs) using published whole transcriptome sequencing data. We predicted their potential targets and competitive endogenous RNA (ceRNA) prediction and analyzed their molecular functions using functional enrichment analysis. Results More differentially expressed lncRNAs (DElncRNAs) were observed in irisin-treated samples. The top irisin-induced lncRNAs were associated with OA or chondrogenic differentiation, including XIST, PAX8-AS1, CASC15, LINC01618, and DLX6-AS1. The DEGs co-expressed with DElncRNAs were enriched in skeletal system development, extracellular matrix (ECM) organization, cell adhesion, and inflammation associated pathways. Several lncRNAs likely acted as ceRNAs to regulate downstream mRNAs including ROR2 and SORBS1 in in OA or chondrogenic differentiation. Conclusions We demonstrate the global regulation of lncRNAs by irisin during chondrogenic differentiation of human MSCs. Further study is required to characterize the key irisin-regulated lncRNAs in chondrogenic differentiation

Abstract I001: Long noncoding RNAs at the intersection of cancer pathways

Abstract There are thousands of long noncoding RNAs (lncRNAs) in mammalian genomes. Yet, their functional significance in health and disease states remains poorly understood. We investigate the intersection of lncRNAs and cancer biology. On the one hand, we dissect the molecular and cellular mechanisms by which lncRNAs modulate cancer pathways. On the other hand, we develop mouse models to interrogate the roles of lncRNAs in tumorigenesis at the organismal level. Our work has uncovered insights into the transcriptional regulatory roles of lncRNAs during the cellular response to genotoxic and oncogenic stress. In parallel, we have elucidated roles of lncRNAs as drivers of tumor progression and metastatic dissemination. The combined functional and mechanistic studies have revealed the importance of lncRNAs in cancer and suggest therapeutic approaches to target lncRNAs or their downstream effectors in cancer. Citation Format: Nadya Dimitrova. Long noncoding RNAs at the intersection of cancer pathways [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr I001.

Expression pattern of long non-coding RNAs in treatment-naïve and medicated schizophrenia patients.

Schizophrenia is a disabling mental disorder that affects 1% of people over their lifetime. The etiology and mechanism of schizophrenia are very complex, and many genes are involved in many different signaling pathways in the etiology of this disease. According to recent studies, one of the important mechanisms altered in this disorder is the regulation of immune system and the inflammation mechanism. In the present study, we evaluated the peripheral blood expression pattern of four lncRNAs and three protein-coding genes in the treatment- naïve patients, and medicated patients compared with sex and age-matched controls. In the medicated-patients, expression levels of IFNG, IL18RAP, AC007278.2 were significantly up-regulated (P < 0.05); and the expression level of IFNG-AS1-001 was significantly down-regulated compared to healthy controls (P < 0.05). However, levels of IL18R1, AC007278.3 and IFNG-AS1-003 were not different between these groups. In the treatment-naïve patients, IFNG, IL18R1, IL18RAP, IFNG-AS1-001, AC007278.2, and AC007278.3 were significantly up-regulated compared to controls. On the other hand, IFNG-AS1-003 was significantly down-regulated in the treatment-naïve patients compared to controls. Based on the Spearman correlation matrix, there was a significant correlation between genes in the treatment-naïve patients. We also showed the high sensitivity and specificity of IFNG-AS1-003, IFNG, IL18R1, and AC007278.3 in the identification of treatment-naïve patients from controls. The current study contributes further evidence to the understanding of the role of lncRNAs in the pathogenesis of schizophrenia. Future research is necessary to establish the validity of lncRNAs as peripheral markers for this condition.

Uncovering functional lncRNAs by scRNA-seq with ELATUS

Long non-coding RNAs (lncRNAs) play fundamental roles in cellular processes and pathologies, regulating gene expression at multiple levels. Despite being highly cell type-specific, their study at single-cell (sc) level is challenging due to their less accurate annotation and low expression compared to protein-coding genes. Here, we systematically benchmark different preprocessing methods and develop a computational framework, named ELATUS, based on the combination of the pseudoaligner Kallisto with selective functional filtering. ELATUS enhances the detection of functional lncRNAs from scRNA-seq data, detecting their expression with higher concordance than standard methods with the ATAC-seq profiles in single-cell multiome data. Interestingly, the better results of ELATUS are due to its advanced performance with an inaccurate reference annotation such as that of lncRNAs. We independently confirm the expression patterns of cell type-specific lncRNAs exclusively detected with ELATUS and unveil biologically important lncRNAs, such as AL121895.1, a previously undocumented cis-repressor lncRNA, whose role in breast cancer progression is unnoticed by traditional methodologies. Our results emphasize the necessity for an alternative scRNA-seq workflow tailored to lncRNAs that sheds light on the multifaceted roles of lncRNAs.

Deciphering the role of LncRNA in alcoholic liver disease: Mechanisms and therapeutic potential.

Alcoholic liver disease (ALD) is a spectrum of liver damage caused by chronic alcohol consumption. The disease progresses in stages, starting with simple fatty liver, progressing to alcoholic hepatitis and potentially leading to fibrosis and cirrhosis. The pathophysiology of ALD is complex and involves several cellular and molecular mechanisms. Recent research has highlighted the role of long non-coding RNAs (LncRNAs) as critical regulators in the development and progression of ALD. This article reviews the current understanding of LncRNAs in ALD, focusing on their functions in key pathological processes and their potential as diagnostic markers and therapeutic targets.

The long non-coding RNA lncRNA-DRNR enhances infectious bronchitis virus replication by targeting chicken JMJD6 and modulating interferon-stimulated genes expression via the JAK-STAT signalling pathway.

Infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis (IB), a severe disease that primarily affects young chickens and poses a significant challenge to the global poultry industry. Understanding the complex interaction between the virus and its host is vital for developing innovative antiviral strategies. Long non-coding RNA (lncRNA) plays a crucial role in regulating host antiviral immune responses. Our previous studies have shown that IBV infection disrupts the stability of lncRNA in host cells, indicating a potential regulatory role for lncRNA in IBV pathogenesis. It is still not clear how lncRNA precisely modulates IBV replication. In this study, we observed down-regulation ofMSTRG.26120.58 (named lncRNA-DRNR) expression in various chicken cell lines upon IBV infection. We demonstrated that silencing lncRNA-DRNR using siRNA enhances intracellular replication of IBV. Through exploring genes encoding proteins upstream and downstream of lncRNA-DRNR within a 100kb range, we identified chJMJD6 (chicken JMJD6) as a potential target gene negatively regulated by lncRNA-DRNR expression levels. Furthermore, chJMJD6 inhibits STAT1 methylation, thereby affecting the induction of interferon-stimulated genes (ISGs) through the activation of the IFN-β-mediated JAK-STAT signalling pathway, ultimately promoting the intracellular replication of IBV. In summary, our findings reveal the critical role played by lncRNA-DRNR during IBV infection, providing novel insights into mechanisms underlying coronavirus-induced disruption in lncRNA stability.

Long non-coding RNAs as prognostic biomarkers in non-muscle invasive bladder cancer: A systematic review

Traditional prognostic tools for non-muscle invasive bladder cancer (NMIBC) often overestimate progression and recurrence risks, underscoring the need for more precise biomarkers. While long non-coding ribonucleic acids (lncRNAs) have been reviewed in bladder cancer, no review has focused on NMIBC. The aim of this study was to address this gap by investigating the role of lncRNAs in predicting NMIBC survival and progression. A systematic review was conducted using PubMed, Scopus, and Cochrane databases as of July 31, 2024. Prognostic studies investigating the association between lncRNA expression and survival outcomes, such as cancer-specific survival, disease-free survival, recurrence-free survival, or overall survival, using Kaplan-Meier curves or hazard ratios, were included. A total of three studies were analyzed, involving 279 NMIBC patients and focusing on three lncRNAs: urothelial cancer associated 1 (UCA1), growth arrest-specific 5 (GAS5), and up-regulated in non-muscle invasive bladder cancer (UNMIBC). Increased UCA1 expression was strongly associated with poor disease-free survival (hazard ratio (HR): 1.974; 95%CI: 1.061–3.673; p=0.032) and progression-free survival (HR: 3.476; 95%CI: 1.187–10.18; p=0.023). Reduced GAS5 expression was significantly associated with poor disease-free survival (HR: 2.659; 95%CI: 1.348–5.576; p=0.005) and progression-free survival (HR: 6.628; 95%CI: 1.494–29.40; p=0.013). Higher level of UNMIBC was strongly associated with poor recurrence-free survival (HR: 2.362; 95%CI: 1.504–4.837; p=0.007). In conclusion, lncRNAs have potential as prognostic biomarkers in NMIBC, with UCA1 and UNMIBC overexpression and GAS5 underexpression being significant in predicting disease recurrence and progression, highlighting the clinical relevance of monitoring these lncRNAs to improve prognosis and guide treatment decisions.

Long Noncoding RNAs Expressed in Mouse Pituitary Development and Mature Hormone-Producing Cells.

Mammalian genomes contain thousands of genes for long noncoding RNA (lncRNAs), some of which have been shown to affect protein coding gene expression through diverse mechanisms. The lncRNA transcripts are longer than 200 nucleotides and are often capped, spliced, and polyadenylated, but not translated into protein. Nuclear lncRNAs can modify chromatin structure and transcription in trans or cis by interacting with the DNA, forming R-loops, and recruiting regulatory proteins. Not much is known about the role of lncRNA in pituitary gland differentiation and function. We mined transcriptome data from mouse pituitary glands collected at embryonic days 12.5 and 14.5 and identified over 200 different lncRNA transcripts. To develop a research resource for the study of lncRNA, we used pituitary cre transgenes to tag pituitary cell types in adult mice with fluorescent markers, and enriched for thyrotropes, gonadotropes, and somatotropes using fluorescence-activated cell sorting. We determined the transcriptome of each cell population using RNA sequencing and mined the data for lncRNA. We detected hundreds of lncRNAs in adult pituitary cells; a few were located immediately nearby genes that encode pituitary hormones or lineage-specific transcription factors. The location of these lncRNAs suggests the possibility of a cis-acting regulatory role in pituitary development or function, and we observe coordinated expression of 2 of them with their putative target genes in transgenic mice. This research resource sets the foundation for examining the actions of lncRNAs on their putative target genes and determining whether they have roles during development and in response to physiological demand.

Distinct Hippocampal Expression Profiles of lncRNAs in Obese Type 2 Diabetes Mice Exhibiting Cognitive Impairment.

Cognitive dysfunction has been accepted as a possible complication of type 2 diabetes (T2D), but few studies revealed the potential roles of Long non‑coding RNAs (lncRNAs) in cognitive dysfunction in T2D. The current research aims to demonstrate the specific expression patterns of lncRNA-mRNA in the hippocampi of T2D db/db mice exhibiting cognitive impairment. In this study, the results from behavioral tests showed that T2D db/db mice displayed short-term and spatial working memory deficits compared to db/m mice. Furthermore, western blot analysis demonstrated that compared with db/m mice, p-GSK3β (ser9) protein levels were markedly elevated in T2D db/db mice (P < 0.01). In addition, though not statistically significant, the ratio of p-Tau (Ser396) to Tau 46, α-Synuclein expression, and p-GSK3α (ser21) expression were also relatively higher in T2D db/db mice than in db/m mice. The microarray profiling revealed that 75 lncRNAs and 26 mRNAs were dysregulated in T2D db/db mice (> 2.0 fold change, P < 0.05). GO analysis demonstrated that the differentially expressed mRNAs participated in immune response, extracellular membrane-bounded organelle, and extracellular region. KEGG analysis revealed that the differentially expressed mRNAs were mainly involved in one carbon pool by folate, glyoxylate and dicarboxylate metabolism, autophagy, glycine, serine and threonine metabolism, and B cell receptor signaling pathway. A lncRNA‑mRNA coexpression network containing 71 lncRNAs and 26 mRNAs was built to investigate the interaction between lncRNA and mRNA. Collectively, these results revealed the differential hippocampal expression profiles of lncRNAs in T2D mice with cognitive dysfunction, and the findings from this study provide new clues for exploring the potential roles of lncRNAs in the pathogenesis of cognitive dysfunction in T2D.

Aortic valve stenosis augments long noncoding RNA H19 to govern angiogenic responses and phenotypes of valvular endothelial cell through endothelial to mesenchymal transition

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as important regulators of cardiovascular disease, including aortic valve stenosis (AVS). Although several recent studies have reported that lncRNAs are dysregulated and might play a crucial role in (Endothelial to mesenchymal transition) EndMT, no specific role of lncRNA was reported in AVS pathogenesis. Here, we sought to investigate the role of H19 in EndMT during the pathogenesis of AVS. Methods and results High-throughput lncRNA sequencing of human aortic valve tissue explanted from patients with AVS due to severe stenosis during surgical aortic valve replacement (SAVR) demonstrated that certain lncRNAs [H19, AGAP2-AS1 (PUNISHER), GAS5, MALAT1] are significantly dysregulated compared to patients without AVS. To validate the RNA-seq data, 60 patients with AVS (n=30) or without AVS (n=30) were prospectively investigated. Among these, H19 (p=0.002), AGAP2-AS1 (p=0.002), and GAS5 (0.02) were significantly upregulated in patients with AVS, compared to non-AVS patients. Aortic valvular endothelial cells (VECs) were isolated from explanted valve tissue from AVS patients or obtained commercially. In vitro EndMT-promoting stimuli (TNFα or TGFß+IL1ß) were used for VEC stimulation for 5 days. RT-qPCR was used to quantify the expression of EndMT markers (EC markers, vWF, and NOS3, and mesenchymal markers, αSMA, SM22, Vimentin, and SNAI2). Loss of H19 led to dysregulation of the EC gene network and protein expression patterns that were analyzed by qRT-PCR, immunoblotting, and immunofluorescence, respectively. Further experiments show that silencing of H19 affects migration and proliferation, and promotes EndMT in EC. Functional assays suggested that H19 is a critical regulator of angiogenic properties. The molecular signature of angiogenesis was investigated using a RT-qPCR-based angiogenesis array to identify the regulation of angiogenesis with 84-angiogenesis-related genes. Mechanistically, the angiogenesis array revealed that H19 regulates Jagged Canonical Notch Ligand 1 (JAG1) (4.43-fold vs. control EC), an important regulator of NOTCH1 signaling, and pro-angiogenic factor in EC. Accordingly, EndMT marker expressions were dysregulated upon H19 depletion. A high-throughput luciferase reporter array demonstrated STAT3 activation upon H19 knockdown. Depletion of H19 increased the phosphorylation of STAT3 at TYR705 and pharmacological inhibition of STAT3 activation abolished the effects of H19 silencing on EndMT marker expression as well as on angiogenesis. Overexpression of H19 in VEC abrogated the H19-mediated promotion of JAG1- and VEGFA gene- and protein expression. Our data suggest that H19 might play a role in EC angiogenic gene expression and EndMT. The data reveal a pivotal role of H19 in controlling EndMT in AVS via regulation of the JAG1-NOTCH axis, which could potentially be therapeutically targeted to halt EndMT during AVS.

Roles of lncRNAs related to the p53 network in breast cancer progression.

The p53 is a crucial tumor suppressor and transcription factor that participates in apoptosis and senescence. It can be activated upon DNA damage to regulate the expression of a series of genes. Previous studies have demonstrated that some specific lncRNAs are part of the TP53 regulatory network. To enhance our understanding of the relationship between lncRNAs and P53 in cancers, we review the localization, structure, and function of some lncRNAs that are related to the mechanisms of the p53 pathway or serve as p53 transcriptional targets.

M1 macrophages deliver CASC19 via exosomes to inhibit the proliferation and migration of colon cancer cells.

Colorectal cancer (CRC) continues to be one of the leading causes of cancer-related death worldwide. Exosomes have been established to play an important role in intercellular communication and that long non-coding RNA (lncRNA) CASC19 is enriched within M1 macrophage-derived exosomes (M1-exo). However, the biological functions and underlying molecular mechanisms of exosomal CASC19 from macrophages on CRC remain unknown. Cell proliferation and migration were evaluated by MTS and transwell assays. The exosomes were characterized by western blot, nanoparticle tracking analysis (NTA) and electron microscope imaging. The expression levels of CASC19 and its putative target miR-410-3p were quantified by reverse-transcription polymerase chain reaction (RT-qPCR). The interaction between CASC19 and miR-410-3p was detected by the pull-down assay. We found that the non-contact inhibition of M1 macrophages on the proliferation of colon cancer cells is largely dependent on the CASC19 released from M1 exosomes. M1 exosomes successfully delivered CASC19 to colon cancer cells, exerting an inhibitory effect on cell proliferation and migration. The exosomes secreted by M1 cells with CASC19 knockdown showed less inhibition effect on cell proliferation and migration. Mechanically, CASC19 exerted an inhibitory effect on colon cancer cells by sponging miR-410-3p via tube morphogenesis and TGF-β signaling pathway. We first proved that CASC19 in M1 macrophages is delivered into colon cancer cells via exosomes, exerting an inhibitory effect on their proliferation and migration by sponging miR-410-3p. The study may provide mechanistic insights into the roles of lncRNAs in CRC progression and a potential therapeutic target for the treatment of CRC.

Long Non-coding RNAs: Potential Diagnostic and Treatment Targets for Non-small Cell Lung Cancer

Abstract: Lung cancer is the leading cause of cancer-related deaths globally, necessitating ongoing scientific research to understand its detection, treatment, and prevention. Long non-coding RNAs (lncRNAs) are a diverse group of non-coding RNAs that play crucial roles in regulating tumorigenic processes, such as cell proliferation, invasion, and metastasis in non-small cell lung cancer (NSCLC). Despite not encoding proteins, lncRNAs have significant impacts on the development and progression of NSCLC. Recent evidence suggests that lncRNAs may serve as valuable biomarkers for diagnosing and prognosticating NSCLC through tissue or blood analysis, and as potential therapeutic targets. This review provides a comprehensive overview of recent advancements in lncRNA research for NSCLC, offering new insights into their mechanisms of action and potential therapeutic applications. It also explores promising avenues for therapeutic development. By elucidating the complex roles of lncRNAs in NSCLC, this article aims to contribute to the development of innovative diagnostic and therapeutic strategies that can significantly enhance patient outcomes. Understanding the multifaceted functions of lncRNAs in lung cancer has the potential to lead to substantial progress in early disease detection, targeted treatments, and personalized medicine, ultimately improving the prognosis and quality of life for individuals affected by this devastating disease.

Schistosoma japonicum infection-mediated downregulation of lncRNA Malat1 contributes to schistosomiasis hepatic fibrosis by the Malat1/miR-96/Smad7 pathway

BackgroundSchistosoma japonicum infection causes hepatic fibrosis, a primary cause of morbidity and mortality associated with the disease, and effective treatments are still lacking. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenic process of various tissue fibroses. However, the role of lncRNAs in schistosomiasis hepatic fibrosis (HF) is poorly understood. Understanding the role of lncRNAs in schistosomiasis HF will enhance knowledge of disease processes and aid in the discovery of therapeutic targets and diagnostic biomarkers.MethodsDifferentially expressed lncRNA profiles in primary hepatic stellate cells (HSCs) of mice infected with S. japonicum were identified using high-throughput lncRNA sequencing. Primary HSCs were isolated from infected mice using collagenase digestion and density-gradient centrifugation, cultured in DMEM with 10% fetal bovine serum. Dual-luciferase reporter assays, nuclear cytoplasm fractionation and RIP assays were employed to assess the relationship between Malat1 and miRNA-96. Malat1 lentivirus and ASO-Malat1 were constructed for forced expression and downregulated expression of Malat1. The Malat1-KO mouse was constructed by CRISPR/Cas9 technology. Pathological features of the liver were evaluated by hematoxylin-eosin (HE), Masson’s trichrome staining and immunohistochemistry (IHC). The expression levels of fibrosis-related genes were determined by quantitative real-time PCR (qRT-PCR) and Western blot.ResultsA total of 1561 differentially expressed lncRNAs were identified between infected and uninfected primary HSCs. Among the top altered lncRNAs, the downregulated Malat1 was observed in infected HSCs and verified by qPCR. Treatment of infected mice with praziquantel (PZQ) significantly increased the Malat1 expression. Elevated Malat1 expression in infected primary HSC reduced the expressions of profibrogenic genes, whereas Malat1 knockdown had the opposite effect. Moreover, Malat1 was found to interact with miR-96, a profibrotic miRNA, by targeting Smad7. Forced Malat1 expression reduced miR-96 levels in infected primary HSCs, attenuating fibrogenesis and showing negative correlation between Malat1 expression and the expression levels of miR-96 and profibrogenic genes α-SMA and Col1α1. Notably, in Malat1-KO mice, knockout of Malat1 aggravates schistosomiasis HF, while restored Malat1 expression in the infected HSCs reduced the expression of profibrogenic genes.ConclusionsWe demonstrate that lncRNA is involved in regulation of schistosomiasis HF. Elevated lncRNA Malat1 expression in infected HSCs reduces fibrosis via the Malat1/miR-96/Smad7 pathway, thus providing a novel therapeutic target for schistosomiasis HF. Furthermore, Malat1 expression is sensitive to PZQ treatment, thus offering a potential biomarker for assessing the response to chemotherapy.Graphical abstract

Dendritic cell-derived lncRNAs in patients with acute coronary syndrome.

Long non-coding RNAs (lncRNAs) and dendritic cells (DC) play crucial roles in the development of acute coronary syndrome (ACS); however, the mechanisms remain unclear. To investigate this, we analysed the differentially expressed lncRNAs in monocyte-derived DCs (moDCs) from patients with ACS. Peripheral blood mononuclear cells were transformed into moDCs. Cellular morphology and expression levels of moDC-specific markers (CD80, CD86, CD11c, CD14 and HLA-DR) were analysed using electron microscopy (EM) and flow cytometry (FCM), respectively. Differentially expressed lncRNAs and their functions were predicted using gene sequencing, gene ontology and the Kyoto Encyclopedia of Genes and Genomes. The expression levels of markers, signalling pathway molecules (p-PI3K and p-AKT), inflammatory cytokines (IL-6 and IL-12p70) and target gene (C-C motif chemokine ligand (CCL) 15 and CCL14) were analysed by overexpression or silencing of candidate lncRNAs. EM revealed the cells to be suspended in dendritic pseudopodia. CD11c and HLA-DR were upregulated, while CD80 and CD86 were downregulated. Comparison between the UA versus ST group showed the highest number of differentially expressed lncRNAs (n = 113), followed by UA versus NST (n = 115), CON versus NST (n = 49) and CON versus ST (n = 35); however, the number was low for CON versus UA and ST versus NST groups. moDC-specific marker expression, signalling pathway molecules, inflammatory cytokines and CCL14 were upregulated following lentiviral overexpression of smart silencer-CCL15-CCL14; however, expression levels decreased following transfection with siRNA. The morphology, function and lncRNA expression of moDCs differ depending on the type of ACS. The differentially expressed lncRNAs, particularly CCL15-CCL14, regulate the function of moDCs. Thus, our study provides new insights regarding the role of lncRNAs in ACS and indicates the potential use of CCL15-CCL14 as a novel diagnostic marker and therapeutic target.

Screening lncRNAs essential for cardiomyocyte proliferation by integrative profiling of lncRNAs and mRNAs associated with heart development

BackgroundThe proliferation potential of mammalian cardiomyocytes declines markedly shortly after birth. Both long non-coding RNAs (lncRNAs) and mRNAs demonstrate altered expression patterns during cardiac development. However, the role of lncRNAs in the cell cycle arrest of cardiomyocytes remains inadequately understood. MethodThe expression pattern of lncRNAs and mRNAs was analyzed in mouse hearts exhibiting varying regenerative potentials on postnatal days (P) 1, 7, and 28. Weighted correlation network analysis (WGCNA) was employed to elucidate the co-expression relationship between lncRNAs and mRNAs. Protein-protein interaction (PPI) network was built using the STRING database, and hub lncRNAs were identified by CytoHubba. Molecular Complex Detection (MCODE) was used to screen core modules of the PPI network in Cytoscape. Upstream lncRNAs and miRNAs which may regulate mRNAs were predicted using miRTarBase and AnnoLnc2, respectively. Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery. ResultsCompared with the P1 heart, 618 mRNAs and 414 lncRNAs displayed.transcriptional changes in the P7 heart, while 2358 mRNAs and 1290 lncRNAs showed from P7 to P28. Gene Ontology (GO) analysis revealed that module 1 in the both comparisons was enriched in the mitotic cell cycle process. 2810408I11Rik and 2010110K18Rik were identified as hub lncRNAs and their effects on the proliferation of cardiomyocytes were verified in vitro. Additionally, four lncRNA-miRNA-mRNA regulatory axes were predicted to explain the mechanism by which 2810408I11Rik and 2010110K18Rik regulate cardiomyocyte proliferation. Notably, the overexpression of 2810408I11Rik enhances cardiomyocyte proliferation and heart regeneration in the adult heart following MI. ConclusionThis study systematically analyzed the landscape of lncRNAs and mRNAs at P1, P7, and P28. These findings may enhance our understanding of the framework for heart development and could have significant implications for heart regeneration.

Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence.

Anticancer chemotherapy (ACT) remains a cornerstone in cancer treatment, despite significant advances in pharmacology over recent decades. However, its associated side effect toxicity continues to pose a major concern for both oncology clinicians and patients, significantly impacting treatment protocols and patient quality of life. Current clinical strategies to mitigate ACT-induced toxicity have proven largely unsatisfactory, leaving a critical unmet need to block toxicity mechanisms without diminishing ACT's therapeutic efficacy. This review aims to document the molecular mechanisms underlying ACT toxicity and highlight research efforts exploring the protective effects of trace elements (TEs) and their nanoparticles (NPs) against these mechanisms. Our literature review reveals that the primary driver of ACT toxicity is redox imbalance, which triggers oxidative inflammation, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, autophagy, and dysregulation of signaling pathways such as PI3K/mTOR/Akt. Studies suggest that TEs, including zinc, selenium, boron, manganese, and molybdenum, and their NPs, can potentially counteract ACT-induced toxicity by inhibiting oxidative stress-mediated pathways, including NF-κB/TLR4/MAPK/NLRP3, STAT-3/NLRP3, Bcl-2/Bid/p53/caspases, and LC3/Beclin-1/CHOP/ATG6, while also upregulating protective signaling pathways like Sirt1/PPAR-γ/PGC-1α/FOXO-3 and Nrf2/HO-1/ARE. However, evidence regarding the roles of lncRNA and the Wnt/β-catenin pathway in ACT toxicity remains inconsistent, and the impact of TEs and NPs on ACT efficacy is not fully understood. Further research is needed to confirm the protective effects of TEs and their NPs against ACT toxicity in cancer patients. In summary, TEs and their NPs present a promising avenue as adjuvant agents for preventing non-target organ toxicity induced by ACT.

Inhibition of the long non-coding RNA MALAT1 downregulates MAP2K1 to suppress the progression of hypopharyngeal squamous cell carcinoma.

This study aimed to explore the role of lncRNA MALAT1 (Long non-coding RNAs metastasis-associated lung adenocarcinoma transcript), and its underlying mechanisms in Hypopharyngeal Squamous Cell Carcinoma (HSCC). Quantitative real-time PCR (qRT-PCR) was employed to measure lncRNA MALAT1 expression in HSCC and adjacent non-cancerous tissues, along with the expression of the downstream target mitogen-activated protein kinase kinase 1 (MAP2K1). The independent prognostic significance of lncRNA MALAT1 was assessed using Cox regression analysis. Potential downstream targets of MALAT1 were identified through PRM analysis and validated using the TCGA-HNSC database, Western blotting, and immunohistochemistry. CCK-8, flow cytometry, and Transwell assays were conducted to assess the effects of the lncRNA MALAT1/MAP2K1 axis on FaDu cells. Additionally, a nude mouse xenograft model was used to confirm the role of lncRNA MALAT1/MAP2K1 in tumor growth. LncRNA MALAT1 was significantly upregulated in HSCC tissues and closely associated with poor prognosis. Bioinformatics analysis, including parallel reaction monitoring (PRM) screening and TCGA-HNSC data, identified FERMT2, CSNK2A2, and MAP2K1 as potential downstream targets of MALAT1. Validation through qPCR, Western blotting, and immunohistochemistry confirmed MAP2K1 as a downstream target. In vitro and in vivo experiments demonstrated that inhibiting lncRNA MALAT1 suppressed cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT) by downregulating MAP2K1 expression. Additionally, it induced apoptosis, affected the cell cycle, and inhibited tumor growth. Our study uniquely demonstrates that targeting MALAT1 significantly impedes HSCC progression by downregulating its novel downstream target, MAP2K1, offering new insights into potential therapeutic strategies.

Profiling the lncRNA–miRNA–mRNA interaction network in the cold-resistant exercise period of grape (Vitis amurensis Rupr.)

BackgroundGrape is a plant that is sensitive to low temperature and vulnerable to low-temperature damage. However, little is known about the roles of lncRNAs, miRNAs and mRNAs in regulating the hypothermia response mechanism in Vitis amurensis Rupr.MethodsIn this study, the expression and regulatory network of low-temperature response genes were studied in the phloem of grape under different low-temperature stress.ResultsHere, we performed analyses related to RNA-seq and miRNA-seq on grape phloem tissues from five periods of cold resistance campaigns. Three RNAs (lncRNAs, miRNAs and mRNAs) obtained by KEGG and GO analyses were used to identify starch and sucrose metabolism associated with cold resistance, and specific changes in BP, CC, and MF were identified in four comparisons. Venn diagrams, thermograms and pathway maps were used to analyze the differentially expressed genes (DEGs), and their specific gene expression during the cold exercise were obtained. The six DEGs finally selected were used for qRT-PCR to verify the RNA-seq data. In addition, we found that the regulatory networks of miRNAs and lncRNAs correspond to the six DEGs. This study will contribute to further experimental studies to elucidate the cold resistance mechanism of Vitis amurensis Rupr.ConclusionsThe low-temperature response genes of grape are mainly enriched in the starch and sucrose metabolism, and they are regulated by miRNAs and lncRNAs. The conclusions will provide basic information for further understanding of the cold resistance mechanism of grape in the future.Graphical