Function Of Non-coding RNAs Research Articles

Long noncoding RNA mediates enzalutamide resistance and transformation in neuroendocrine prostate cancer

Prostate cancer is a malignant tumor caused by the malignant proliferation of epithelial cells, which is highly heterogeneous and drug-resistant, and neuroendocrine prostate cancer (NEPC) is an essential cause of drug resistance in its late stage. Elucidating the evolution of NEPC and the resistance process of enzalutamide, a novel antiandrogen, will be of great help in improving the prognosis of patients. As a research hotspot in the field of molecular biology in recent years, the wide range of biological functions of long noncoding RNAs (lncRNAs) has demonstrated their position in the therapeutic process of many diseases, and a large number of studies have revealed their critical roles in tumor progression and drug resistance. Therefore, elucidating the involvement of lncRNAs in the formation of NEPCs and their interrelationship with enzalutamide resistance may provide new ideas for a deeper understanding of the development of this disease and the occurrence of enzalutamide resistance and give a new direction for reversing the therapeutic dilemma of advanced prostate cancer. This article focuses on lncRNAs that regulate enzalutamide resistance and the neuroendocrine transition of prostate cancer through epigenetic, androgen receptor (AR) signaling, and non-AR pathways that act as “molecular sponges” interacting with miRNAs. Some insights into these mechanisms are used to provide some help for subsequent research in this area.

The role of disulfidptosis-associated LncRNA-LINC01137 in Osteosarcoma Biology and its regulatory effects on macrophage polarization.

The objective of this research is to investigate the function of long non-coding RNA (lncRNA) associated with disulfidptosis, particularly LINC01137, in osteosarcoma (OS), and its impact on macrophage polarization and the tumor immune microenvironment (TME), with the goal of identifying new prognostic biomarkers and therapeutic targets. Utilizing the OS transcriptome dataset from the TARGET database, differentially expressed lncRNAs related to disulfidptosis were identified. The functional mechanisms of LINC01137, which affect cell proliferation, migration, invasiveness, programmed cell death, and macrophage orientation, were explored using the full suite of analyses provided by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), alongside a diverse array of laboratory experiments, including an in vivo osteosarcoma xenograft model in BALB/c nude mice to assess the impact of LINC01137 knockdown on tumor growth. Among three lncRNAs identified that were distinctly linked to disulfidptosis, LINC01137 showed a notable increase in expression within OS cell lines. Silencing LINC01137 led to a marked decrease in the abilities of cell proliferation, migration, and invasiveness, simultaneously enhancing programmed cell death and facilitating the process of epithelial-mesenchymal transition (EMT). In vivo experiments further confirmed that LINC01137 knockdown significantly suppressed tumor growth in osteosarcoma xenograft models, aligning with the in vitro findings. Associated with disulfidptosis, LINC01137 is pivotal in osteosarcoma development through its enhancement of tumor cell proliferation, migration, and invasiveness, as well as its modification of macrophage orientation within the TME. Given its significance, LINC01137 merits exploration as a prognostic indicator, necessitating detailed studies on its regulatory functions and potential in therapy.

Regulation and functions of long non-coding RNAs during Meloidogyne incognita parasitism of tomato.

Long non-coding RNAs (lncRNAs) are emerging as important regulators of various aspects of immune response and plant-pathogen interactions. However, the regulatory function of lncRNAs during plant-nematode interaction remain largely elusive. In this study, we investigated the differential regulation and function of lncRNAs during two different stages of tomato infection by the root-knot nematode Meloidogyne incognita. At the early stage of infection, 2218 and 2827 lncRNAs were regulated locally in the M. incognita-induced galls and systemically in the neighboring root cells, respectively. However, at the later stage of infection, the number of M. incognita-regulated lncRNAs was dramatically reduced with only 49 lncRNA being identified as differentially expressed. Differentially expressed lncRNAs were predicted to encode peptides with functionally annotated domains, providing insights into the potential roles of these peptides in regulating gene expression, RNA stability and splicing, and protein-protein-interactions. Among the differentially expressed lcRNAs, 55 were found to contain putative binding sites for 56 miRNAs. Overexpressing 5 of these lncRNAs significantly increased tomato resistance to M. incognita, supporting the functional importance of lncRNAs for establishing tomato-M. incognita interaction. Functional analysis of the target mimicry of lncRNAs towards miRNAs resulted in the identification of two novel regulatory modules involving miR47 and miR156e-5p and their targeted genes that regulate tomato responses to M. incognita parasitism. Taken together, our data provide novel insights into the transcriptional and post-transcriptional regulatory functions of lncRNA, and open a new avenue to engineer crop plants with enhanced nematode resistance by leveraging the regulatory potential of lncRNAs.

Function of noncoding RNA in regulating cancer cell plasticity

Recent advances have brought non-coding RNAs (ncRNAs) into the spotlight, revealing their critical regulatory roles in cancer cell plasticity. ncRNAs, such as microRNAs (miRNAs), transfer RNAs (tRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are now recognized as key players in cellular processes such as chromatin remodeling, mRNA stability, and translation. This review delves into the diverse functions of ncRNAs in stem cells and cancer stem cells (CSCs) biology, emphasizing their impact on maintaining and modulating cellular states. We explore the mechanisms by which ncRNAs influence stem cell self-renewal and differentiation, including their roles in establishing pluripotency and directing differentiation. In the context of cancer, ncRNAs are pivotal in driving processes like epithelial-mesenchymal transition (EMT), which underlies metastasis and therapy resistance. By regulating gene expression and epigenetic landscapes, ncRNAs sustain the dynamic nature of CSCs, facilitating tumor growth and heterogeneity. The review also highlights the potential clinical applications of ncRNAs as biomarkers and therapeutic targets. Advances in ncRNA detection and manipulation have opened new avenues for developing diagnostic tools and innovative treatments. Liquid biopsies, which utilize ncRNAs from biological fluids, provide a minimally invasive approach to monitor tumor dynamics and progression. Uncovering the intricate networks regulated by ncRNAs makes it evident that these molecules play central roles in understanding cancer cell plasticity. Insights into their functions offer promising strategies for targeted cancer therapies, aiming to disrupt the adaptability of cancer cells and improve treatment outcomes.

Bacterial small RNA makes a big impact for gut colonization

The functions of non-coding small RNAs (sRNAs) within the human microbiome remain largely unexplored. In this Cell Host & Microbe issue, El Mouali etal. identify Segatella RNA colonization factor (SrcF), a sRNA from a prevalent gut bacterium Segatella copri. SrcF promotes colonization of S.copri by regulating bacterial degradation of complex dietary carbohydrates.

The TCONS_00046732/chi-miR-135b-5p/PRLR regulatory axis promotes endometrial epithelial cells growth through the PI3K-Akt signaling pathway

Non-coding RNAs are considered key regulatory factors in biological and reproductive physiological processes in mammals. However, the molecular functions of long noncoding RNAs (lncRNAs) in regulating dynamic uterine development and reproductive capacity during sexual maturation remain unclear. This study analyzed the expression characteristics and molecular functions of lncRNAs in uterine tissues from 20 goats at four specific time points during sexual maturation: day 1 after birth (D1), 2 months (M2), 4 months (M4), and 6 months (M6), finding that stage-specific DE lncRNAs may regulate cell proliferation, apoptosis, hormone secretion, metabolism, and immune response through multiple action modes. Within the lncRNA-miRNA-mRNA network, a novel lncRNA, TCONS_00046732, associated with uterine development, exhibited significantly higher expression during sexual maturity compared to the prepubertal stage, correlating positively with PRLR and negatively with chi-miR-135b-5p. FISH and IF analyses revealed significant co-localization and distinct expression patterns of TCONS_00046732, chi-miR-135b-5p, and PRLR in the endometrial epithelium. Further experiments confirmed that TCONS_00046732 competitively binds to chi-miR-135b-5p to upregulate PRLR, thereby activating the PI3K-Akt signaling pathway, promoting primary endometrial epithelial cell proliferation, G1-to-S phase transition, and inhibiting apoptosis. These findings enhance our understanding of uterine molecular regulation and provide key insights into the molecular basis of goat sexual development.

First person – Kyoung-Min Choi

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Kyoung-Min Choi is co-first author on ‘ Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release’, published in JCS. Kyoung-Min is an Associate Research Scholar in the lab of Je-Hyun Yoon at the College of Medicine, University of Oklahoma, investigating the functions of noncoding RNAs in metabolic disorders.

Transcriptome-wide association study discovers functional long non-coding RNAs in coronary artery disease

Abstract Genetically regulated long non-coding RNAs (lncRNAs) in coronary artery disease (CAD) have not been investigated. To discover CAD-relevant lncRNAs, we performed the transcriptome-wide association study (TWAS) using a subset genomic data of CARDIoGRAMplusC4D Consortium and transcriptomic data of nine CAD-relevant tissue types from Genotyped Tissue Expression (GTEx) and Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) projects. We identified 20 lncRNAs associated with CAD in a tissue-specific fashion. The eQTL-GWAS colocalization analysis associated 15 lncRNAs with cardiometabolic traits which could bridge the lncRNA to CAD risk. The co-expression analysis identified co-expressed protein-coding genes of 16 lncRNAs and suggested their involved biological pathways. Four antisense lncRNAs from the same locus, CDH13-AS2, CDH13-AS1, CEDORA, and CTD-3253I12.1, not only shared cardiometabolic traits but also exclusively co-expressed with the host gene, CDH13. Our biological experiments using dRfxCas13d-based RNA immunoprecipitation, CRISPR/Cas9 gene knockdown, and dCas9-VP64-based transcriptional activation in endothelial cells, elucidated CDH13-AS2 as a stabilizer of CDH13 mRNA and suggested therapeutic potential of CDH13-AS2 overexpression.

Altered expression of long noncoding RNAs regulating neutrophilic inflammation in peripheral blood was associated with symptom severity in patients with house dust mite-induced allergic rhinitis.

Long noncoding RNAs (lncRNAs) have been implicated in a diverse array of human immune diseases; however, a comprehensive understanding of the expression and function of lncRNAs in the peripheral blood leukocytes of individuals suffering from house dust mite (HDM)-induced allergic rhinitis (AR) remains elusive. To explore the potential roles and functions of long noncoding RNAs (lncRNAs) in the pathogenesis of AR. Sequencing analysis was performed on peripheral blood leukocytes collected from patients with HDM-induced AR and healthy controls (HCs) to elucidate the expression patterns of lncRNAs. Differentially expressed (DE) lncRNAs were identified and validated, and further correlation analyses were conducted to explore their associations with visual analog scale (VAS) scores and cytokine levels in the serum and nasal secretions. Additionally, bioinformatics analyses were performed to predict the potential pathways influenced by DE lncRNAs. Finally, the diagnostic potential of these lncRNAs in AR was assessed via receiver operating characteristic (ROC) curve analysis. Significant differences in the expression profiles of lncRNAs and mRNAs were detected between AR patients and HCs. Four lncRNAs were markedly upregulated in AR patients. AC011524.2 was positively correlated with nasal pruritus (r = 0.4492, P = 0.0411). AL133371.3 was positively correlated with runny nose (r = 0.4889, P = 0.0245). AC011524.2 was positively correlated with CXCL8 (r = 0.4504, P = 0.0035). AL133371.3 was significantly positively correlated with only IL-17 (r = 0.4028, P = 0.0100). IL-4 in the serum was positively related to IL-17 in the serum (r = 0.4163, P = 0.0002). CXCL5 in the serum was positively correlated with IFN-γ (r = 0.3336, P = 0.0354) in nasal secretions. The area under the curve (AUC) of the ROC curve resulting from the integration of the 4 lncRNAs exhibited a remarkable value of 0.940 for AR diagnosis. Our results identified several lncRNAs associated with AR symptoms and inflammatory cytokines. Specifically, AC011524.2 and AL133371.3 exhibited strong correlations with diverse AR manifestations and serum cytokines, suggesting their pivotal role in the pathogenesis of AR, likely via neutrophil- and Th17-related pathways. However, the precise underlying mechanisms are still elusive, necessitating further exploration.

METTL3-induced lncARSR aggravates neuroblastoma tumorigenic properties through stabilizing PHOX2B

Neuroblastoma (NB), the most common extracranial solid tumor in pediatric patients, manifests with considerable variability across multiple primary sites. Despite this, the extent of genetic heterogeneity within these tumor foci and the identification of consistent oncogenic drivers remains largely unexplored. Of particular interest, genetic mutations in PHOX2B have been linked to familial cases of NB, yet the underlying molecular mechanisms are not fully delineated. In our research, we focus on unraveling the role of a novel functional long non-coding RNA (lncRNA) associated with PHOX2B in the context of NB. Using NB cell models with overexpressed PHOX2B, combined with lncRNA microarray analysis, we discovered that lncARSR is significantly upregulated in response to PHOX2B overexpression. Subsequent biological assays demonstrated that lncARSR promotes both the proliferation and metastasis of NB cells. Further molecular investigations revealed that lncARSR plays a crucial role in stabilizing PHOX2B expression within NB cells. Moreover, we identified that the expression of lncARSR is regulated by methylation through methyltransferase-like 3 (METTL3), which itself is positively correlated with PHOX2B expression. Rescue experiments underscored the functional importance of METTL3, lncARSR, and PHOX2B in NB cells. In summary, our findings provide new insights into the molecular functions of PHOX2B in the progression of neuroblastoma and propose a novel therapeutic target for this aggressive malignancy.

Identification of a Plasma Exosomal lncRNA- and circRNA-Based ceRNA Regulatory Network in Patients With Lung Adenocarcinoma.

Exosomes have been established to be enriched with various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) that exert various biological effects. However, the lncRNA- and circRNA-mediated coexpression competing endogenous RNA (ceRNA) regulatory network in exosomes derived from the plasma of patients with lung adenocarcinoma (LUAD) remains elusive. This study enrolled nine patients with lung adenocarcinoma and three healthy individuals, and the differential expression of messenger RNAs (mRNAs), lncRNAs, and circRNAs was detected using microarray analysis, while microRNAs (miRNAs) were detected through RNA sequencing. Additionally, bioinformatics algorithms were applied to evaluate the lncRNA-miRNA-mRNAs/circRNA-miRNA-mRNA network. Differentially expressed cicRNAs were identified via quantitative reverse transcription polymerase chain reaction (RT-qPCR). A total of 1016 lncRNAs, 1396 circRNAs, 45 miRNAs, and 699 mRNAs were differentially expressed in the plasma exosomes of patients with LUAD compared with healthy controls. Among them, 881 lncRNAs were upregulated and 135 were downregulated, 916 circRNAs were upregulated while 480 were downregulated, 45 miRNAs were upregulated while none were downregulated, and 591 mRNAs were upregulated while 108 were downregulated (p ≤ 0.05, and fold change ≥ 2). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the biological functions of differentially expressed RNAs. Meanwhile, the RNA networks displayed the regulatory relationship between dysregulated RNAs. Finally, RT-qPCR validated that the expression of circ-0033861, circ-0043273, and circ-0011959 was upregulated in the plasma exosome of patients with LUAD compared to healthy controls (p = 0.0327, p = 0.0002, p = 0.0437, respectively). This study proposed a newly discovered ncRNA-miRNA-mRNA/circRNA-miRNA-mRNA ceRNA network and identified that the expression of circulating circ-0033861, circ-0043273, and circ-0011959 was up-regulated in the plasma exosomes of patients with LUAD, offering valuable insights for exploring the potential function of exosomal noncoding RNA and identifying potential biomarkers for LUAD.

Identifying functional cuproptosis-related long non-coding RNAs in patients with bladder cancer.

Bladder cancer is the most common malignancy of the urinary tract and one of the most common cancers in the world. Cuproptosis is a novel type of cell death associated with tumorigenesis. In this study, we assessed the correlation between cuproptosis-related genes and tumorigenesis. Moreover, we constructed a prognostic signature. Pearson correlation analysis and univariate Cox regression were utilized to extract cuproptosis-related long non-coding RNAs (lncRNAs) predicting prognosis in The Cancer Genome Atlas (TCGA) database. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to establish a cuproptosizs-related prognostic signature. A nomogram signature was generated to predict individual survival. We obtained 19 cuproptosis-related genes and 14 prognostic cuproptosis-related lncRNAs. We constructed a seven-prognostic risk signature. Time-dependent receiver operating characteristic (ROC) curves demonstrated good predictive power (1-, 3-, and 5-year survival rates of 0.711, 0.673, and 0.684, respectively). The high-risk group reported a worse prognosis than the low-risk group, and the risk signature was identified as an independent factor. The biological process of risk-related genes primarily involved tumorigenesis and migration. The high-risk group expressed high chemokines and T cell inhibition and low antigen-presenting cells. Cuproptosis-related lncRNAs are central to tumorigenesis, providing a novel therapeutic target for patients with bladder cancer. We constructed an individualized predictive signature based on cuproptosis-related lncRNAs.

Expression patterns of housekeeping genes and tissue-specific genes in black goats across multiple tissues

Black goats are a significant meat breed in southern China. To investigate the expression patterns and biological functions of genes in various tissues of black goats, we analyzed housekeeping genes (HKGs), tissue-specific genes (TSGs), and hub genes (HUBGs) across 23 tissues. Additionally, we analyzed HKGs in 13 tissues under different feeding conditions. We identified 2968 HKGs, including six important ones. Interestingly, HKGs in grazing black goats demonstrated higher and more stable expression levels. We discovered a total of 9912 TSGs, including 134 newly identified ones. The number of TSGs for mRNA and lncRNA were nearly equal, with 127 mRNA TSGs expressed solely in one tissue. Additionally, the predicted functions of tissue-specific long non-coding RNAs (lncRNAs) targeting mRNAs corresponded with the physiological functions of the tissues.Weighted gene co-expression network analysis (WGCNA) constructed 30 modules, where the dark grey module consists almost entirely of HKGs, and TSGs are located in modules most correlated with their respective tissues. Additionally, we identified 289 HUBGs, which are involved in regulating the physiological functions of their respective tissues. Overall, these identified HKGs, TSGs, and HUBGs provide a foundation for studying the molecular mechanisms affecting the genetic and biological processes of complex traits in black goats.

LncRNA-HMG incites colorectal cancer cells to chemoresistance via repressing p53-mediated ferroptosis

Upon chemotherapy, excessive reactive oxygen species (ROS) often lead to the production of massive lipid peroxides in cancer cells and induce cell death, namely ferroptosis. The elimination of ROS is pivotal for tumor cells to escape from ferroptosis and acquire drug resistance. Nevertheless, the precise functions of long non-coding RNAs (lncRNAs) in ROS metabolism and tumor drug-resistance remain elusive. In this study, we identify LncRNA-HMG as a chemoresistance-related lncRNA in colorectal cancer (CRC) by high-throughput screening. Abnormally high expression of LncRNA-HMG predicts poorer prognosis in CRC patients. Concurrently, we found that LncRNA-HMG protects CRC cells from ferroptosis upon chemotherapy, thus enhancing drug resistance of CRC cells. LncRNA-HMG binds to p53 and facilitates MDM2-mediated degradation of p53. Decreased p53 induces upregulation of SLC7A11 and VKORC1L1, which contribute to increase the supply of reducing agents and eliminate excessive ROS. Consequently, CRC cells escape from ferroptosis and acquire chemoresistance. Importantly, inhibition of LncRNA-HMG by anti-sense oligo (ASO) dramatically sensitizes CRC cells to chemotherapy in patient-derived xenograft (PDX) model. LncRNA-HMG is also a transcriptional target of β-catenin/TCF and activated Wnt signals trigger the marked upregulation of LncRNA-HMG. Collectively, these findings demonstrate that LncRNA-HMG promotes CRC chemoresistance and might be a prognostic or therapeutic target for CRC.

Construction of Prognostic ceRNA Network Landscape in Breast Cancer to Explore Impacting Genes on Drug Response by Integrative Bioinformatics Analysis

Background: Breast cancer accounts for 30% of all new female cancers yearly. Bioinformatics serves us to find new biomarkers and facilitate future experimental research. Exploring a distinct network of competing endogenous RNA (ceRNA) that includes potential prognostic, diagnostic, and therapeutic biomarkers is captivating. Methods: Differentially expressed lncRNAs, mRNAs, and miRNAs were collected using Gene Expression Omnibus datasets. DEGs were validated based on TCGA. Functional analysis and pathway activity were also done. Drug sensitivity analyses were done, and IC50 vs. gene expression plots were depicted. Results: A total of 696 mRNAs, 48 lncRNAs, and, 43 miRNAs were identified to have significant differential expression in cancerous breast tissue than normal breast tissue samples. Functional analysis showed significant pathway enrichments in cancer. We found that 13 individual genes, lncRNAs, and miRNAs, CDC6, ERBB2, EZR, HELLS, MAPK13, MCM2, MMP1, SLC7A5, TINCR, TRIP13, hsa-miR-376a, hsa-miR-21, hsa-miR-454 were significantly predictive of poor overall survival and AKAP12, CXCL12, FGF2, IRS2, LINC00342, LINC01140, MEG3, MIR250HG, NAV3, NDRG2, NEAT1, TGFBR3 and, hsa-miR-29c were associated with favorable overall survival. We reached a set of five genes (EGR1, NFIB, TGFBR3, SMARCA4, and MCM2) that exhibit altered expression patterns in breast cancer, resulting in increased susceptibility of cancer cells to certain drug treatments. Conclusion: We successfully made a unique ce-network, providing new clues to understand the regulatory functions of non-coding RNAs (miRNAs and lncRNAs) in the pathogenesis and prognosis of breast cancer and will facilitate further experimental studies to develop new biomarkers in the diagnosis, prognosis and, therapy of breast cancer.

The construction and experimental verification of a 6-LncRNA model based on Lactic acid metabolism in the tumor microenvironment of Wilms tumor

BackgroundLactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear. MethodsGene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified. ResultsThe immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor’s development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells. ConclusionThis study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.

A disulfidptosis-associated long noncoding RNA signature to predict low-grade glioma classification, prognosis, tumor microenvironment, and therapy regimens: Observational study.

This study aimed to investigate the function of disulfidptosis-associated long noncoding RNAs (DAlncRNAs) in low-grade gliomas (LGG) through bioinformatics analysis and construct a signature to predict the classification, prognosis, tumor microenvironment, and selection of immunotherapy and chemotherapy in LGG. Genomic, clinical, and mutational information of 526 patients with LGG was retrieved from The Cancer Genome Atlas repository. A nonnegative matrix factorization algorithm was applied to classify patients with LGG. Univariate, LASSO regression, and multivariate Cox regression analyses were performed to determine prognostic DAlncRNAs. Following the median risk score, we defined the sample as a high-risk (HR) or low-risk group. Finally, survival, receiver operating characteristic curve, risk curve, principal component, independent prognosis, risk difference, functional enrichment, tumor microenvironment, immune cell infiltration, mutation, and drug sensitivity analyses were performed. Patients were classified into C1 and C2 subtypes associated with disulfidptosis. Eight prognostic DAlncRNAs (AC003035.2, AC010157.2, AC010273.3, AC011444.3, AC092667.1, AL450270.1, AL645608.2, and LINC01571) were identified, and a prognostic signature of LGG was developed. The DAlncRNA-based signature was found to be an independent prognostic factor in patients with LGG, thereby constructing a nomogram. In addition, in the HR group, immune function was more active and the tumor mutation burden was higher. The patients were mainly composed of subtype C2, and their prognosis was worse. Immunotherapy and chemotherapy were predicted in the HR and low-risk groups, respectively. Our study, based on DAlncRNAs, highlights 2 disulfidptosis-associated LGG subtypes with different prognostic and immune characteristics and creates a novel disulfidptosis-associated prognostic signature, which may inform the classification, prognosis, molecular pathogenesis, and therapeutic strategies for patients with LGG.

Unveiling axolotl transcriptome for tissue regeneration with high-resolution annotation via long-read sequencing

Axolotls are known for their remarkable regeneration ability. Exploring their transcriptome provides insight into regenerative mechanisms. However, the current annotation of the axolotl transcriptome is limited, leaving the role of unannotated transcripts in regeneration unknown. To discourse this challenge, we exploited long-read sequencing technology, which enables direct observation of full-length RNA transcripts, greatly enhancing the coverage and accuracy of axolotl transcriptome annotation. By utilizing this method, we identified 222 novel gene loci and 4775 novel transcripts, which were quantified using short-read sequencing data. Through the inclusive analysis, we discovered novel homologs, potential functional proteins, noncoding RNAs, and alternative splicing events in key regeneration pathways. In particular, we identified novel transcripts with high protein-coding potential implicated in cell cycle regulation and musculoskeletal development, and regeneration were identified. Interestingly, alternative splice variants were also detected across diverse pathways critical to regeneration. This specifies that these novel transcripts potentially play vital roles underpinning the robust regenerative capacities of axolotls. Single-cell transcriptomic analysis further revealed these isoforms to predominantly exist in axolotl limb chondrocytes and mature tissue cell populations. Overall, the findings significantly advanced consideration of the axolotl transcriptome and provided a new perspective for understanding the mechanisms of regenerative abilities of axolotls.

Unraveling the influence of LncRNA in gastric cancer pathogenesis: a comprehensive review focus on signaling pathways interplay.

Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/β-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets.

Function and Therapeutic Potential of Non-Coding RNA in Ameloblastoma.

Ameloblastoma (AB) is a common odontogenic tumor that develops in the mouth. Despite its benign nature, AB exhibits significant invasiveness leading to tumor metastasis and high postoperative recurrence rates. Studies have shown a relationship between the occurrence and development of various tumors and non-coding RNA (ncRNA). NcRNA, transcribed from the genomes of mammals and other complex organisms, are often products of alternative splicing and processing into smaller products. MicroRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) are the main types of ncRNA. NcRNA play increasingly significant roles in the pathogenesis of human cancers, regulating their occurrence and progression as oncogenes or tumor suppressors. They are involved in tumor development and progression through alternative splicing of pre-mRNA, transcriptional regulation, mRNA stability, protein translation, and chromatin remodeling and modification. The importance of ncRNA in AB has received significant attention in recent years. However, the biological functions and mechanisms of ncRNA in AB remain largely unknown. In this review, we not only explore the functions and roles of ncRNA in AB, but also describe and envision their potential functional roles as biomarkers in AB diagnosis. In particular, we highlight the potential of miR-29a as a molecular marker for diagnosis and therapy. As promising novel therapeutic targets, the biological functions of ncRNA need further study, which is indispensable.