The lncRNA UCA1 Enhances Pancreatic Cancer EMT by Regulating miR-708-5p and miR-135b-5p: A Bioinformatics Approach.

Background: Pancreatic cancer (PC) is an exceedingly malignant ailment that is not only characterized by its insidious onset and rapid progression but also by its poor therapeutic effects. Recently, emerging evidence has shed light on the significant role that non-coding RNAs (ncRNAs), particularly long ncRNAs (lncRNAs) and microRNAs (miRNAs), play in the pathogenesis of PC. This investigation aimed to construct a network of interactions between miRNAs, lncRNAs, and mRNAs, as well as to perform correlation analyses in the context of PC. Methods: This study carried out in Kerman City, southeastern Iran in 2023. We utilized the GSE119794 dataset from the Gene Expression Omnibus (GEO) to analyze differentially expressed lncRNAs (DE-lncRNAs), miRNAs (DE-miRNAs), and mRNAs (DE-mRNAs). Following the identification of the DE-lncRNAs, DE-mRNAs, and DE-miRNAs, we proceeded to examine differentially expressed epithelialmesenchymal transition (EMT) genes. Subsequently, we utilized the RNAInter database to predict interactions among lncRNAs, miRNAs, and mRNAs. Finally, we employed Cytoscape to visualize and analyze the constructed network. Results: 14 DE-lncRNAs, 14 DE-miRNAs, 545 DE-mRNAs, and 65 DE-EMT from pancreatic cancer and its adjacent tissue RNA-Seq data were identified. 1184 EMT genes from dbEMT were obtained, among which 65 DE-EMT were assigned as EMT genes and correlated with tumor progression. One functional lncRNA (UCA1) was identified as a key functional lncRNA. The area under the ROC curve (AUC) of UCA1 and miR-708-5p were 0.79 and 0.86, respectively. Thus, it is reasonable to believe that this prognostic risk model helps predict PC metastasis. Conclusion: UCA1 is a new lncRNA linked with EMT in PC and contributes to a better knowledge of the regulatory mechanisms related to lncRNAs in PC.

Plasma-derived exosomal long noncoding RNAs of pancreatic cancer patients as novel blood-based biomarkers of disease.

BACKGROUND: Pancreatic cancer (PaCa) is one of the most intractable and fatal malignancies and is associated with the dysregulation of long noncoding RNAs (lncRNAs), which are a large class of noncoding RNAs larger than 200 nt that act as competing endogenous RNAs or sponges for miRNAs to induce tumour biological behaviours. However, their clinical value in treating pancreatic cancer has been poorly explained, but they are essential for improving the prognosis of PaCa patients. METHODS: We analysed the plasma-derived exosomal lncRNA profiles of PaCa patients by using whole-transcriptome sequencing analysis and identified significantly differentially expressed lncRNAs, including LINC01268, LINC02802, AC124854.1, and AL132657.1. In the current study, the expression levels of four plasma-derived exosomal lncRNAs in PaCa plasma were validated via quantitative real-time polymerase chain reaction (qRT‒PCR). The relationship between the expression of the four lncRNAs and the clinicopathological features of patients with PaCa was also evaluated. RESULTS: We demonstrated that exosomal LINC01268, LINC02802, AC124854.1 and AL132657.1 were highly expressed in PaCa plasma compared with those in normal controls; moreover, they were positively correlated with the serum expression of carbohydrate antigen 19-9 (CA19-9). The receiver operating characteristic curves (AUCs) of the four lncRNAs were 0.8421, 0.6544, 0.7190, and 0.6321, and the AUC value of the combination of the four exosomal lncRNAs increased to 0.8476, with a sensitivity of 0.72 and specificity of 0.89. These results suggested that the plasma-derived exosomal genes LINC01268, LINC02802, AC124854.1, and AL132657.1 may be novel diagnostic markers for PaCa. CONCLUSIONS: Our research demonstrated that the plasma-derived exosomal lncRNAs of PaCa patients are novel blood-based biomarkers of disease.

Xist RNA binds select autosomal genes and depends on Repeat B to regulate their expression.

Xist, a pivotal player in X chromosome inactivation (XCI), has long been perceived as a cis-acting long noncoding RNA that binds exclusively to the inactive X chromosome (Xi). However, Xist's ability to diffuse under select circumstances has also been documented, leading us to suspect that Xist RNA may have targets and functions beyond the Xi. Here, using female mouse embryonic stem cells (ES) and mouse embryonic fibroblasts (MEF) as models, we demonstrate that Xist RNA indeed can localize beyond the Xi. However, its binding is limited to ~100 genes in cells undergoing XCI (ES cells) and in post-XCI cells (MEFs). The target genes are diverse in function but are unified by their active chromatin status. Xist binds discretely to promoters of target genes in neighborhoods relatively depleted for Polycomb marks, contrasting with the broad, Polycomb-enriched domains reported for human XIST RNA. We find that Xist binding is associated with down-modulation of autosomal gene expression. However, unlike on the Xi, Xist binding does not lead to full silencing and also does not spread beyond the target gene. Over-expressing Xist in transgenic ES cells similarly lead to autosomal gene suppression, while deleting Xist's Repeat B motif reduces autosomal binding and perturbs autosomal down-regulation. Furthermore, treating female ES cells with the Xist inhibitor, X1, leads to loss of autosomal suppression. Altogether, our findings reveal Xist targets ~100 genes beyond the Xi, identify Repeat B as a crucial domain for its in-trans function in mice, and indicate that autosomal targeting can be disrupted by the X1 small molecule inhibitor.

Long non-coding RNA NEAT1 induced by BHLHE40 activates Wnt/ß-catenin signaling and potentiates colorectal cancer progression.

BACKGROUND: Nuclear-enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), has been implicated in the colorectal cancer (CRC) progression. However, its upstream mechanism has not been well studied. In the present study, the functions and mechanisms of NEAT1 in CRC were investigated. METHODS: The NEAT1 expression in CRC tissues and CRC cells was analyzed by RT-qPCR. The genes co-expressed with NEAT1 in CRC were obtained from UALCAN, which were intersected with the transcription factors targeting NEAT1 from hTFtarget. Dual-luciferase assay, RT-qPCR, and ChIP were conducted to analyze the transcriptional regulatory relationship between BHLHE40 and NEAT1. LoVo and HCT-15 cells knocking down BHLHE40 and overexpressing NEAT1 were subjected to MTT, Transwell, Western blot, and flow cytometry to examine the malignant aggressiveness of CRC cells. The effects of knocking down BHLHE40 and overexpressing NEAT1 on tumor and lung metastasis were investigated in mice using HE and immunohistochemical analyses. RESULTS: NEAT1 and BHLHE40 were significantly overexpressed in CRC tissues and cells. BHLHE40 has a binding relationship with the NEAT1 promoter. Knockdown of BHLHE40 resulted in a reverted malignant phenotype in vitro and slowed tumor growth and metastasis dissemination in vivo, which were reversed by NEAT1 overexpression. Overexpression of BHLHE40 increased Wnt/ß-catenin pathway activity, but knockdown of NEAT1 decreased Wnt/ß-catenin pathway activity. CONCLUSIONS: BHLHE40 mediates the transcriptional activation of NEAT1, which activates the Wnt/ß-catenin pathway and promotes the CRC progression.

LincRNA-p21/AIF-1/CMPK2/NLRP3 pathway promoted inflammation, autophagy and apoptosis of human tubular epithelial cell induced by urate via exosomes.

Urate nephropathy, a common complication of hyperuricemia, has garnered increasing attention worldwide. However, the exact pathogenesis of this condition remains unclear. Currently, inflammation is widely accepted as the key factor in urate nephropathy. Therefore, the aim of this study was to elucidate the interaction of lincRNA-p21/AIF-1/CMPK2/NLRP3 via exosomes in urate nephropathy. This study evaluated the effect of lincRNA-p21/AIF-1/CMPK2/NLRP3 using clinical data collected from patients with urate nephropathy and human renal tubular epithelial cells (HK2) cultured with different concentrations of urate. In clinical research section, the level of lincRNA-p21/AIF-1 in exosomes of urine in patients with hyperuricemia or urate nephropathy was found to be increased, particularly in patients with urate nephropathy. In vitro study section, the level of exosomes, inflammation, autophagy, and apoptosis was increased in HK2 cells induced by urate. Additionally, the expression of lincRNA-p21, AIF-1, CMPK2, and NLRP3 was upregulated in exosomes and HK2 cells. Furthermore, manipulating the activity of lincRNA-p21, AIF-1, CMPK2, and NLRP3 through overexpression or interference vectors regulated the level of inflammation, autophagy, and apoptosis in HK2 cells. In conclusion, the pathway of lincRNA-p21/AIF-1/CMPK2/NLRP3 contributed to inflammation, autophagy, and apoptosis of human renal tubular epithelial cell induced by urate via exosomes. Additionally, the specific exosomes in urine might serve as novel biomarkers for urate nephropathy.

A novel lncRNA GM47544 modulates triglyceride metabolism by inducing ubiquitination-dependent protein degradation of APOC3.

OBJECTIVE: Emerging evidence highlights the pivotal roles of long non-coding RNAs (lncRNAs) in lipid metabolism. Apoprotein C3 (ApoC3) is a well-established therapeutic target for hypertriglyceridemia and exhibits a strong association with cardiovascular disease. However, the exact mechanisms via which the lncRNAs control ApoC3 expression remain unclear. METHODS: We identified a novel long noncoding RNA (lncRNA), GM47544, within the ApoA1/C3/A4/A5 gene cluster. Subsequently, the effect of GM47544 on intracellular triglyceride metabolism was analyzed. The diet-induced mouse models of hyperlipidemia and atherosclerosis were established to explore the effect of GM47544 on dyslipidemia and plaque formation in vivo. The molecular mechanism was explored through RNA sequencing, immunoprecipitation, RNA pull-down assay, and RNA immunoprecipitation. RESULTS: GM47544 was overexpressed under high-fat stimulation. GM47544 effectively improved hepatic steatosis, reduced blood lipid levels, and alleviated atherosclerosis in vitro and in vivo. Mechanistically, GM47544 directly bound to ApoC3 and facilitated the ubiquitination at lysine 79 in ApoC3, thereby facilitating ApoC3 degradation via the ubiquitin-proteasome pathway. Moreover, we identified AP006216.5 as the human GM47544 transcript, which fulfills a comparable function in human hepatocytes. CONCLUSIONS: The identification of GM47544 as a lncRNA modulator of ApoC3 reveals a novel mechanism of post-translational modification, with significant clinical implications for the treatment of hypertriglyceridemia and atherosclerosis.

LncRNA NPTN-IT1-201 Ameliorates Depressive-like Behavior by Targeting miR-142-5p and Regulating Inflammation and Apoptosis via BDNF.

OBJECTIVE: Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are widely expressed in the brain and are associated with the development of neurological and neurodegenerative diseases. However, their roles and molecular mechanisms in major depressive disorder (MDD) remain largely unknown. This study aimed to identify lncRNAs and miRNAs involved in the development of MDD and elucidate their molecular mechanisms. METHODS: Transcriptome and bioinformatic analyses were performed to identify miRNAs and lncRNAs related to MDD. C57 mice were subjected to chronic unpredictable mild stress (CUMS) to establish a depression model. Lentiviruses containing either lncRNA NPTN-IT1-201 or miR-142-5p were microinjected into the hippocampal region of these mice. Behavioral tests including the sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST) were conducted to evaluate depressive-like behaviors. RESULTS: The results revealed that overexpression of lncRNA NPTN-IT1-201 or inhibition of miR-142-5p significantly ameliorated depressive-like behaviors in CUMS-treated mice. Dual-luciferase reporter assays confirmed interactions between miR-142-5p with both brain-derived neurotrophic factor (BDNF) and NPTN-IT1-201. ELISA analysis revealed significant alterations in relevant biomarkers in the blood samples of MDD patients compared to healthy controls. Histological analyses, including HE and Nissl staining, showed marked structural changes in brain tissues following CUMS treatment, which were partially reversed by lncRNA NPTN-IT1-201 overexpression or miR-142-5p inhibition. Immunofluorescence imaging demonstrated significant differences in the levels of BAX, Bcl2, p65, Iba1 among different treatment groups. TUNEL assays confirmed reduced apoptosis in brain tissues following these interventions. Western blotting showed the significant differences in BDNF, BAX, and Bcl2 protein levels among different treatment groups. CONCLUSION: NPTN-IT1-201 regulates inflammation and apoptosis in MDD by targeting BDNF via miR-142-5p, making it a potential therapeutic target for MDD.

LincR-PPP2R5C Deficiency Alleviates Airway Remodeling by Inhibiting Epithelial-Mesenchymal Transition Through the PP2A/TGF-ß1 Signaling Pathway in Chronic Experimental Allergic Asthma.

Airway remodeling is a key characteristic of allergic asthma. Epithelial-mesenchymal transition (EMT) induced by various factors, particularly transforming growth factor (TGF)-ß1, orchestrates airway remodeling. Protein phosphatase 2A (PP2A), an important serine-threonine phosphatase, is involved in TGF-ß1 production and EMT. Long noncoding RNAs (lncRNAs) have emerged as novel players in regulating EMT. Here, we aimed to explore the effects and mechanisms of action of lincR-PPP2R5C, a lncRNA that affects PP2A activity, on airway remodeling in a mouse model of chronic allergic asthma. LincR-PPP2R5C knockout (KO) alleviated inflammatory responses in house dust mite (HDM)-induced chronic allergic asthma. Moreover, airway remodeling and EMT were reduced in lung tissues of lincR-PPP2R5C KO mice. HDM extract induced EMT in airway epithelial cells, which was decreased following lincR-PPP2R5C KO. Mechanistically, lincR-PPP2R5C deficiency enhanced PP2A activity, which inhibited TGF-ß1 production in epithelial cells. In conclusion, lincR-PPP2R5C deficiency prevented HDM-induced airway remodeling in mice by reversing EMT, which was mediated by the PP2A/TGF-ß1 signaling pathway. Thus, lncRNAs, i.e., lincR-PPP2R5C, may be potential targets to prevent airway remodeling in allergic asthma.

Phosphate deficiency alters transcript isoforms via alternative transcription start sites.

Alternative transcription start sites (TSS) are widespread in eukaryotes and can alter the 5' UTR length and coding potential of transcripts. Here we show that inorganic phosphate (Pi) availability regulates the usage of several alternative TSS in Arabidopsis (Arabidopsis thaliana). In comparison to phytohormone treatment, Pi had a pronounced and specific effect on the usage of many alternative TSS. By combining short-read RNA sequencing with long-read sequencing of full-length mRNAs, we identified a set of 45 genes showing alternative TSS under Pi deficiency. Alternative TSS affected several processes, such as translation via the exclusion of upstream open reading frames present in the 5' UTR of RETICULAN LIKE PROTEIN B1 mRNA, and subcellular localization via removal of the plastid transit peptide coding region from the mRNAs of HEME OXYGENASE 1 and SULFOQUINOVOSYLDIACYLGLYCEROL 2. Several alternative TSS also generated shorter transcripts lacking the coding potential for important domains. For example, the EVOLUTIONARILY CONSERVED C-TERMINAL REGION 4 (ECT4) locus, which encodes an N6-methyladenosine (m6A) reader, strongly expressed under Pi deficiency a short noncoding transcript (named ALTECT4) ~550 nt long with a TSS in the penultimate intron. The specific and robust induction of ALTECT4 production by Pi deficiency led to the identification of a role for m6A readers in primary root growth in response to low phosphate that is dependent on iron and is involved in modulating cell division in the root meristem. Our results identify alternative TSS usage as an important process in the plant response to Pi deficiency.

ncRNA-mediated SOX4 overexpression correlates with unfavorable outcomes and immune infiltration in hepatocellular carcinoma.

BACKGROUND: The activity and number of immune cells in the tumor microenvironment are closely related to the overall survival of patients with hepatocellular carcinoma (HCC). The sex-determining region Y-box 4 (SOX4) gene is abnormally expressed in various tumor tissues and is critical for tumor development. However, the correlation between SOX4 expression in HCC and tumor immunity is unclear. METHODS: SOX4 expression was explored using data from The Cancer Genome Atlas, and UALCAN databases. Real-time reverse transcription quantitative and western blotting were used to analyze SOX4 expression in several liver cancer cell lines. Additionally, correlations among SOX4 expression, cancer immune characteristics, and infiltrated immune cell gene marker sets in patients with HCC were analyzed using data from the Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, and Tumor-Immune System Interactions databases. Moreover, we evaluated SOX4 expression in HCC tissues and the correlation of SOX4 expression with survival rate. Subsequently, noncoding RNAs (ncRNAs) responsible for SOX4 overexpression were identified using expression, correlation, and survival analyses. RESULTS: SOX4 expression was significantly upregulated in HCC and correlated with a poor prognosis. Additionally, SOX4 upregulation in HCC positively correlated with immune cell infiltration, several biomarkers of immune cells, and immune checkpoint expression. Finally, the MCM3AP-AS1/hsa-miR-204-5p axis was identified as the most likely upstream ncRNA-related pathway for SOX4 in HCC. These results indicated that ncRNA-mediated upregulation of SOX4 correlated with the immune infiltration level and poor prognosis in HCC. Our findings provide new directions for the development of novel immunotherapeutic targets for HCC.

ATR/Chk1 interacting lncRNA modulates DNA damage response to induce breast cancer chemoresistance.

The ATR-Chk1 pathway is essential in cellular responses to DNA damage and replication stress, whereas the role of long noncoding RNAs (lncRNAs) in regulating this pathway remains largely unknown. In this study, we identify an ATR and Chk1 interacting lncRNA (ACIL, also known as LRRC75A-AS1 or SNHG29), which promotes the phosphorylation of Chk1 by ATR upon DNA damages. High ACIL levels are associated with chemoresistance to DNA damaging agents and poor outcome of breast cancer patients. ACIL knockdown sensitizes breast cancer cells to DNA damaging drugs in vitro and in vivo. ACIL protects cancer cells against DNA damages by inducing cell cycle arrest, stabilizing replication forks and inhibiting unscheduled origin firing, thereby guarding against replication catastrophe and contributing to DNA damage repair. These findings demonstrate a lncRNA-dependent mechanism of activating the ATR-Chk1 pathway and highlight the potential of utilizing ACIL as a predictive biomarker for chemotherapy sensitivity, as well as targeting ACIL to reverse chemoresistance in breast cancer.

LncRNA BC200 promotes the development of EBV-associated nasopharyngeal carcinoma by competitively binding to miR-6834-5p to upregulate TYMS expression.

Nasopharyngeal carcinoma (NPC) is closely related to Epstein-Barr virus (EBV) infection. Long noncoding RNAs (lncRNAs) play important roles in cancers. However, the molecular mechanism underlying the roles of lncRNAs in EBV-associated NPC remains largely unclear. In this study, we confirmed that the expression of the lncRNA brain cytoplasmic 200 (BC200) was significantly increased in EBV-infected NPC cells and tissues. BC200 facilitated the growth and migration of NPC cells, suggesting that it participated in NPC progression by functioning as an oncogene. Mechanistically, BC200 was found to act as a ceRNA by sponging and inhibiting miR-6834-5p. Thymidylate synthetase (TYMS), whose high expression was reported to be an independent indicator of poor prognosis in NPC via an unknown mechanism, was identified as a target gene of miR-6834-5p in the present study. BC200 upregulated TYMS expression in a manner that depends on miR-6834-5p. TYMS was abnormally upregulated in EBV-positive NPC cells and tissues, and the ectopic expression contributed to the proliferation and migration of NPC cells. This study highlights the role of lncRNA BC200, which is upregulated by EBV, in promoting the development of NPC, suggesting that BC200-mediated ceRNA network may be valuable biomarkers for the diagnosis and treatment of EBV-associated NPC.

Role of Extracellular Vesicle-Derived Noncoding RNAs in Diabetic Kidney Disease.

Background: Diabetic kidney disease (DKD), a metabolism-related syndrome characterized by abnormal glomerular filtration rate, proteinuria, and renal microangiopathy, is one of the most common forms of chronic kidney disease, whereas extracellular vesicles (EVs) have been recently evidenced as a novel cell communication player in DKD occurrence and progress via releasing various bioactive molecules, including proteins, lipids, and especially RNA, among which noncoding RNAs (including miRNAs, lncRNAs, and circRNAs) are the major regulators. However, the functional relevance of EV-derived ncRNAs in DKD is to be elucidated. Summary: Studies have reported that EV-derived ncRNAs regulate gene expression via a diverse range of regulatory mechanisms, contributing to diverse phenotypes related to DKD progression. Furthermore, there are already many potential clinical diagnostic and therapeutic studies based on these ncRNAs, which can be expected to have potential applications in clinical practice for EV-derived ncRNAs. Key Messages: In the current review, we summarized the mechanistic role of EVs in DKD according to biological function classifications, including inflammation and oxidative stress, epithelial-mesenchymal transition, cell death, and extracellular matrix deposition. In addition, we comprehensively discussed the potential applications of EV-derived ncRNAs as diagnostic biomarkers and therapeutic targets in DKD.

MicroRNA expression profile in the basal plate of human placenta associates with spontaneous preterm birth.

INTRODUCTION: MicroRNAs regulate post-transcriptional gene expression. Their expression has been linked to many pregnancy complications, including preterm birth. Placental microRNA levels differ between preterm and term pregnancies. Not much is known about the targets that are affected by these differences in microRNA expression. We investigated associations between microRNA expression levels in the basal plate of the placenta and their targets and the onset of preterm birth. METHODS: MiRNAomes of spontaneous preterm (n = 6) and term (n = 6) placentas were characterized using RNA sequencing. MicroRNA target and enrichment analyses were performed to explore potential gene targets and pathways. Selected findings were validated using qPCR (n = 41). MicroRNA mimic transfection and luciferase reporter assays were performed to test if certain microRNAs regulate their predicted target, SLIT2, the expression of which has been shown to associate with preterm birth. RESULTS: We identified 39 differentially expressed microRNAs from the preterm placentas compared to term. Many downregulated microRNAs were from the placenta-specific C14MC microRNA cluster. Target gene and pathway analyses showed that microRNAs that associate with preterm birth target transcription related factors and genes linked with protein binding and invasive pathways. Eight of the identified microRNAs putatively target SLIT2, including miR-766-3p and miR-489-3p. Luciferase reporter assay suggested that these microRNAs regulate SLIT2 expression. DISCUSSION: MicroRNA expression changes are associated with spontaneous preterm birth. A group of microRNAs targeting the same gene or genes belonging to the same pathway can have a significant effect on the critical processes maintaining pregnancy and placental functions.

An experimental study to estimate the early postmortem interval based on the degradation of lncRNAs in rat brain tissue.

To study the degradation of lncRNAs in EPMI in rat brain tissue, this study provides a new direction for the estimation of EPMI. LncRNA high-throughput sequencing was performed on the brain tissues of hemorrhagic shock model rats at 0 h and 24 h, and the target lncRNAs were screened. Samples at 0, 1, 3, 6, 12, 18 and 24 h after death were collected, and miRNA-9 and miRNA-125b were used as reference genes. The relative expression levels of lncRNAs at each PMI were detected by RT-qPCR, and a functional model involving lncRNAs and EPMI was established. Samples were collected at 6, 9, 15, and 21 h after death for functional model verification. The expression of several lncRNAs decreased with the prolongation of EPMI, and the mathematical model established by several lncRNA indices exhibited good fit. The verification results of the multi-index joint function model are significantly better than those of the single-index function model, and the established model is more practical. There is a linear relationship between lncRNAs and EPMI, and the multi-index function model is significantly better than the single-index function model, which is important for EPMI inference in forensic pathology practice.

Antisense Oligonucleotide Embedded Context Responsive Nanoparticles Derived from Synthetic Ionizable Lipids for lncRNA Targeted Therapy of Breast Cancer.

The long noncoding RNAs (lncRNA) are primarily associated with several essential gene regulations but are also connected to cancer metabolism and progression. HOTAIR and MALAT1 are two such lncRNAs that are detected in malignancies of various origins and are responsible for the poor prognosis of cancer patients. Due to these factors, the lncRNAs have emerged as prime targets for the development of anticancer therapeutics. However, nonviral delivery of lncRNA-targeted antisense oligonucleotides (ASOs) still remains a critical challenge while maintaining their structural and functional integrity. Herein, we have designed and synthesized a new series of ionizable lipids with variations in their head groups to prepare lipid nanoparticle (LNP) formulation along with cholesterol-based twin cationic lipid and amphiphilic zwitterionic lipid. The context responsiveness of these formulations in delivering the ASOs has been thoroughly investigated by various bioanalytical techniques, and an optimum formulation has been identified. The LNPs are utilized to deliver the ASOs targeting HOTAIR lncRNA in human cancer cell lines and MALAT1 lncRNA in mouse models. This study thus standardizes an advanced nanomaterial system for nonviral gene delivery that has been validated by a considerable reduction in the target lncRNA level under in vitro and a significant reduction in tumor volume under in vivo settings.

Cuproptosis-Related lncRNA Predict Prognosis and Immune Response of LUAD.

Background: Lung cancer is the leading cause of cancer deaths worldwide, primarily due to lung adenocarcinoma (LUAD). However, the heterogeneity of programmed cell death results in varied prognostic and predictive outcomes. This study aimed to develop an LUAD evaluation marker based on cuproptosis-related lncRNAs. Methods: First, transcriptome data and clinical data related to LUAD were downloaded from the Cancer Genome Atlas (TCGA), and cuproptosis-related genes were analyzed to identify cuproptosis-related lncRNAs. Univariate, LASSO, and multivariate Cox regression analyses were conducted to construct cuproptosis-associated lncRNA models. LUAD patients were categorized into high-risk and low-risk groups using prognostic risk values. Kaplan-Meier analysis, PCA, GSEA, and nomograms were employed to evaluate and validate the results. Results: 7 cuproptosis-related lncRNAs were identified, and a risk model was created. High-risk tumors exhibited cuproptosis-related gene alterations in 95.54% of cases, while low-risk tumors showed alterations in 85.65% of cases, mainly involving TP53. The risk value outperformed other clinical variables and tumor mutation burden as a predictor of 1-, 3-, and 5-year overall survival. The cuproptosis-related lncRNA-based risk model demonstrated high validity for LUAD evaluation, potentially influencing individualized treatment approaches. Expression analysis of four candidate cuproptosis-related lncRNAs (AL606834.1, AL161431.1, AC007613.1, and LINC02835) in LUAD tissues and adjacent normal tissues revealed significantly higher expression levels of AL606834.1 and AL161431.1 in LUAD tissues, positively correlating with tumor stage, lymph node metastasis, and histopathological grade. Conversely, AC007613.1 and LINC02835 exhibited lower expression levels, negatively correlating with these factors. High expression of AL606834.1 and AL161431.1 indicated poor prognosis, while low expression of AC007613.1 and LINC02835 was associated with unfavorable outcomes. Univariate and multivariate analyses confirmed these lncRNAs as independent risk factors for LUAD prognosis. Conclusion: The 4 cuproptosis-related (lncRNAsAL606834.1, AL161431.1, AC007613.1, and LINC02835) can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.

LncRNAs are involved in regulating ageing and age-related disease through the adenosine monophosphate-activated protein kinase signalling pathway.

A long noncoding RNA (lncRNA) is longer than 200 bp. It regulates various biological processes mainly by interacting with DNA, RNA, or protein in multiple kinds of biological processes. Adenosine monophosphate-activated protein kinase (AMPK) is activated during nutrient starvation, especially glucose starvation and oxygen deficiency (hypoxia), and exposure to toxins that inhibit mitochondrial respiratory chain complex function. AMPK is an energy switch in organisms that controls cell growth and multiple cellular processes, including lipid and glucose metabolism, thereby maintaining intracellular energy homeostasis by activating catabolism and inhibiting anabolism. The AMPK signalling pathway consists of AMPK and its upstream and downstream targets. AMPK upstream targets include proteins such as the transforming growth factor ß-activated kinase 1 (TAK1), liver kinase B1 (LKB1), and calcium/calmodulin-dependent protein kinase ß (CaMKKß), and its downstream targets include proteins such as the mechanistic/mammalian target of rapamycin (mTOR) complex 1 (mTORC1), hepatocyte nuclear factor 4α (HNF4α), and silencing information regulatory 1 (SIRT1). In general, proteins function relatively independently and cooperate. In this article, a review of the currently known lncRNAs involved in the AMPK signalling pathway is presented and insights into the regulatory mechanisms involved in human ageing and age-related diseases are provided.