Functions Of lncRNAs Research Articles

Integrated analysis of long non-coding RNAs and mRNAs associated with condyloma acuminatum.

Condyloma acuminatum (CA) is a prevalent sexually transmitted disease caused by low-risk human papillomavirus infection, characterized by high transmission and recurrence rates. Long non-coding RNAs (lncRNAs) play a crucial role in regulating gene transcription and are involved in various biological processes. Although recent studies have demonstrated the involvement of lncRNAs in cervical cancer, their expression profile and function in CA remain poorly understood. In this study, we aimed to identify messenger RNA (mRNA) and lncRNA expression patterns in CA using high-throughput lncRNA sequencing. We found that 3033 differentially expressed genes (DEGs) and 1090 differentially expressed lncRNAs (DELs) were significantly altered in CA compared to healthy controls. The results from quantitative reverse transcription polymerase chain reaction and immunohistochemical staining are in accordance with the observed trends in the sequencing data. Functional enrichment analysis revealed that upregulated DEGs in CA were involved in biological processes such as virus response, immune response, cell cycle regulation, the tumor necrosis factor signaling pathway, and the P53 signaling pathway. Co-expression network analysis identified potential target genes of DELs, with enrichment in biological processes such as cell differentiation, the intrinsic apoptotic signaling pathway, and pathways such as virus infection, pathways in cancer, T helper 17 cell differentiation, the mitogen-activated protein kinase signaling pathway, and the Wnt signaling pathway. Collectively, our findings indicate significant changes in the transcriptome profile, including mRNAs and lncRNAs, in CA compared to healthy controls. Our study provides new insights into the potential functions of lncRNAs in the pathogenesis of CA and identifies potential therapeutic targets for this disease.

Bioinformatics-Based Screening of Key LncRNAs for Modulating the Transcriptome Associated with Glaucoma in Human Trabecular Meshwork Cells.

The morphology and functions of the human trabecular meshwork (HTM) are dysregulated in glaucoma, and the molecular mechanisms of this dysregulation remain unknown. According to an established in vitro model, whose function was to study the regulatory networks sustaining the response of HTM cells to the increased substrate stiffness, we systematically analyzed the expression pattern of long noncoding RNAs (lncRNAs), the important regulatory RNAs in cells. Bioinformatics analysis was performed to identify the dysregulated lncRNAs in response to increased substrate stiffness using transcriptome sequencing data (RNA-seq). Then we interfered with the expression of several dysregulated lncRNAs in HTM cells to explore their molecular targets. The cross-linking immunoprecipitation and sequencing method (CLIP-seq) was used to identify enhancer of zeste homolog 2 (EZH2)-targeted RNAs in HTM cells. The chromatin IP and sequencing method (ChIP-seq) was used to identify the targets of EZH2 and histone H3 at lysine 27 (H3K27me3). The response of thousands of dysregulated lncRNAs to increased substrate stiffness was identified through RNA-seq. Functional prediction of these lncRNAs revealed that they potentially regulated key biological processes, including extracellular matrix (ECM) organization. By interfering with the expression of lncRNA SHNG8, ZFHX4-AS1, and RP11-552M11.4, the results demonstrated that those lncRNAs extensively regulated the expression levels of ECM-associated genes. Moreover, we found that EZH2 expression was significantly decreased at high substrate stiffness. Using CLIP-seq to identify EZH2-targeted RNAs in HTM cells, we found that SNHG8 was bound by EZH2. According to the CLIP-seq data of EZH2, we found that EZH2 binding sites were observed in the transcripts of SNHG8-regulated genes, but not in the ChIP-seq results of EZH2 and H3K27me3. Our results suggest that SNHG8 and EZH2 may cooperate to regulate the expression of a subset of genes by influencing their RNA abundance, explaining how they support HTM cell morphology and high density. This study contributes to the understanding of the alteration of HTM during the progression of glaucoma by identifying functional lncRNAs, especially SNHG8, and suggests novel therapeutic targets to treat glaucoma.

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

BackgroundLong non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns render them attractive biomarkers and therapeutic targets. Yet, the functional roles of most lncRNAs remain enigmatic. To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with other genetic features to generate a machine learning model, which we have called INFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Resources).MethodsINFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) screens across seven cell lines, and the algorithm was based on 71 genetic features. To validate the predictions, we selected candidate lncRNAs in the human K562 leukemia cell line and determined the impact of their knockdown (KD) on cell proliferation and chemotherapeutic drug response. We further performed transcriptomic analysis for candidate genes. Based on these findings, we assessed the lncRNA small nucleolar RNA host gene 6 (SNHG6) for its role in myeloid differentiation. Finally, we established a mouse K562 leukemia xenograft model to determine whether SNHG6 KD attenuates tumor growth in vivo.ResultsThe INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nearly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. In this respect, our cell-based and transcriptomic analyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation, SNHG6 transcription is regulated by hematopoiesis-associated transcription factors. SNHG6 KD reduced the proliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte differentiation. Using a xenograft mouse model, we demonstrate that SNHG6 KD attenuated tumor growth in vivo.ConclusionsOur approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell type-specific manner, but also identified new lncRNAs with roles in hematopoiesis and leukemia. Such approaches can be readily applied to identify novel targets for precision medicine.

Potential Intersections between lncRNA, Vascular Cognitive Impairment, and Immunization Strategies: Insights and Future Directions.

Vascular cognitive impairment (VCI) encompasses a wide range of cognitive disorders stemming from cerebrovascular issues, such as strokes or small vessel disease. These conditions often pose challenges to traditional diagnostic approaches due to their multifactorial nature and varied clinical presentations. Recently, next-generation sequencing (NGS) technologies have provided detailed analyses of long non-coding RNAs (lncRNAs) in the molecular pathobiology of VCI. These new findings help with molecular-based diagnostics and treatments of VCI. Within this realm, the concept of immune modulation, especially through specific vaccinations, emerges as a promising therapeutic strategy in VCI mitigation. In this review, we comprehensively elucidate the function of lncRNAs in VCI, emphasizing the advanced understanding of VCI's molecular underpinnings made possible through NGS technologies. Significant focus is placed on the immune system's role in VCI, particularly the neuroinflammatory processes which are consequential to cerebrovascular abnormalities. We believe that lncRNAs participate in regulating these immunological pathways, potentially guiding the development of vaccines targeting VCI. In this context, we propose a novel perspective: using knowledge about lncRNA profiles and functions to guide vaccine development, we can potentially exploit the body's immune response to mitigate or prevent VCI. This approach has the potential to revolutionize VCI management by introducing targeted immunization strategies informed by molecular signatures, a concept that remains largely unexplored in current research endeavors. In addition, we summarize current progress and propose future directions, advocating for robust, interdisciplinary studies to validate the potential intersections between lncRNA landscapes, VCI pathology, and immunology. This review aims to spur innovative research and promote the development of lncRNA-informed vaccine strategies as proactive interventions against the cognitive consequences of VCI.

Conceptual breakthroughs of the long noncoding RNA functional system and its endogenous regulatory role in the cancerous regime.

Long noncoding RNAs (lncRNAs) derived from noncoding regions in the human genome were once regarded as junks with no biological significance, but recent studies have shown that these molecules are highly functional, prompting an explosion of studies on their biology. However, these recent efforts have only begun to recognize the biological significance of a small fraction (< 1%) of the lncRNAs. The basic concept of these lncRNA functions remains controversial. This controversy arises primarily from conventional biased observations based on limited datasets. Fortunately, emerging big data provides a promising path to circumvent conventional bias to understand an unbiased big picture of lncRNA biology and advance the fundamental principles of lncRNA biology. This review focuses on big data studies that break through the critical concepts of the lncRNA functional system and its endogenous regulatory roles in all cancers. lncRNAs have unique functional systems distinct from proteins, such as transcriptional initiation and regulation, and they abundantly interact with mitochondria and consume less energy. lncRNAs, rather than proteins as traditionally thought, function as the most critical endogenous regulators of all cancers. lncRNAs regulate the cancer regulatory regime by governing the endogenous regulatory network of all cancers. This is accomplished by dominating the regulatory network module and serving as a key hub and top inducer. These critical conceptual breakthroughs lay a blueprint for a comprehensive functional picture of the human genome. They also lay a blueprint for combating human diseases that are regulated by lncRNAs.

Genome-scale pan-cancer interrogation of lncRNA dependencies using CasRx

Although long noncoding RNAs (lncRNAs) dominate the transcriptome, their functions are largely unexplored. The extensive overlap of lncRNAs with coding and regulatory sequences restricts their systematic interrogation by DNA-directed perturbation. Here we developed genome-scale lncRNA transcriptome screening using Cas13d/CasRx. We show that RNA targeting overcomes limitations inherent to other screening methods, thereby considerably expanding the explorable space of the lncRNAome. By evolving the screening system toward pan-cancer applicability, it supports molecular and phenotypic data integration to contextualize screening hits or infer lncRNA function. We thereby addressed challenges posed by the enormous transcriptome size and tissue specificity through a size-reduced multiplexed gRNA library termed Albarossa, targeting 24,171 lncRNA genes. Its rational design incorporates target prioritization based on expression, evolutionary conservation and tissue specificity, thereby reconciling high discovery power and pan-cancer representation with scalable experimental throughput. Applied across entities, the screening platform identified numerous context-specific and common essential lncRNAs. Our work sets the stage for systematic exploration of lncRNA biology in health and disease.

Roles of lncRNAs in NF-κB-Mediated Macrophage Inflammation and Their Implications in the Pathogenesis of Human Diseases.

Over the past century, molecular biology's focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types, including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity. It orchestrates gene expression related to immune responses, inflammation, cell survival, and proliferation. Consequently, its malfunction is a key contributor to the onset and development of these diseases. This review aims to summarize the function of lncRNAs in regulating NF-κB activity in macrophage activation and inflammation, with a particular emphasis on their relevance to human diseases and their potential as therapeutic targets. The insights gained from studies on macrophage lncRNAs, as discussed in this review, could provide valuable knowledge for the development of treatments for various pathological conditions involving macrophages.

Denaturing purifications demonstrate that PRC2 and other widely reported chromatin proteins do not appear to bind directly to RNA in vivo

Polycomb repressive complex 2 (PRC2) is reported to bind to many RNAs and has become a central player in reports of how long non-coding RNAs (lncRNAs) regulate gene expression. Yet, there is a growing discrepancy between the biochemical evidence supporting specific lncRNA-PRC2 interactions and functional evidence demonstrating that PRC2 is often dispensable for lncRNA function. Here, we revisit the evidence supporting RNA binding by PRC2 and show that many reported interactions may not occur invivo. Using denaturing purification of invivo crosslinked RNA-protein complexes in human and mouse cell lines, we observe a loss of detectable RNA binding to PRC2 and chromatin-associated proteins previously reported to bind RNA (CTCF, YY1, and others), despite accurately mapping bona fide RNA-binding sites across others (SPEN, TET2, and others). Taken together, these results argue for a critical re-evaluation of the broad role of RNA binding to orchestrate various chromatin regulatory mechanisms.

Interaction between lncRNAs and RNA-binding proteins (RBPs) influences DNA damage response in cancer chemoresistance.

The DNA damage response (DDR) is a crucial cellular signaling pathway activated in response to DNA damage, including damage caused by chemotherapy. Chemoresistance, which refers to the resistance of cancer cells to the effects of chemotherapy, poses a significant challenge in cancer treatment. Understanding the relationship between DDR and chemoresistance is vital for devising strategies to overcome this resistance and improve treatment outcomes. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that do not code for proteins but play important roles in various biological processes, including cancer development and chemoresistance. RNA-binding proteins (RBPs) are a group of proteins that bind to RNA molecules and regulate their functions. The interaction between lncRNAs and RBPs has been found to regulate gene expression at the post-transcriptional level, thereby influencing various cellular processes, including DDR signaling pathways. Multiple studies have demonstrated that lncRNAs can interact with RBPs to modulate the expression of genes involved in cancer chemoresistance by impacting DDR signaling pathways. Conversely, RBPs can regulate the expression and function of lncRNAs involved in DDR. Exploring these interactions can provide valuable insights for the development of innovative therapeutic approaches to overcome chemoresistance in cancer patients. This review article aims to summarize recent research on the interaction between lncRNAs and RBPs during cancer chemotherapy, with a specific focus on DDR pathways.

Nanomaterials-Based Targeting of Long Non-Coding RNAs in Cancer: A Cutting-Edge Review of Current Trends.

This review article spotlights the burgeoning potential of using nanotherapeutic strategies to target long non-coding RNAs (lncRNAs) in cancer cells. This updated discourse underlines the prominent role of lncRNAs in instigating cancer, facilitating its progression, and metastasis, validating lncRNAs' potential for being effective diagnostic biomarkers and therapeutic targets. The manuscript offers an in-depth examination of different strategies presently employed to modulate lncRNA expression and function for therapeutic purposes. Among these strategies, Antisense Oligonucleotides (ASOs), RNA interference (RNAi) technologies, and the innovative clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing tools garner noteworthy mention. A significant section of the review is dedicated to nanocarriers and their crucial role in drug delivery. These nanocarriers' efficiency in targeting lncRNAs in varied types of cancers is elaborated upon, validating the importance of targeted therapy. The manuscript culminates by reaffirming the promising prospects of targeting lncRNAs to enhance the accuracy of cancer diagnosis and improve treatment efficacy. Consequently, new paths are opened to more research and innovation in employing nanotherapeutic approaches against lncRNAs in cancer cells. Thus, this comprehensive manuscript serves as a valuable resource that underscores the vital role of lncRNAs and the various nano-strategies for targeting them in cancer treatment. Future research should also focus on unraveling the complex regulatory networks involving lncRNAs and identifying fundamental functional interactions to refine therapeutic strategies targeting lncRNAs in cancer.

Long Non-Coding RNAs: New Insights in Neurodegenerative Diseases.

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are gradually becoming a burden to society. The adverse effects and mortality/morbidity rates associated with these NDDs are a cause of many healthcare concerns. The pathologic alterations of NDDs are related to mitochondrial dysfunction, oxidative stress, and inflammation, which further stimulate the progression of NDDs. Recently, long non-coding RNAs (lncRNAs) have attracted ample attention as critical mediators in the pathology of NDDs. However, there is a significant gap in understanding the biological function, molecular mechanisms, and potential importance of lncRNAs in NDDs. This review documents the current research on lncRNAs and their implications in NDDs. We further summarize the potential implication of lncRNAs to serve as novel therapeutic targets and biomarkers for patients with NDDs.

Unveiling Polysomal Long Non-Coding RNA Expression on the First Day of Adipogenesis and Osteogenesis in Human Adipose-Derived Stem Cells.

Understanding the intricate molecular mechanisms governing the fate of human adipose-derived stem cells (hASCs) is essential for elucidating the delicate balance between adipogenic and osteogenic differentiation in both healthy and pathological conditions. Long non-coding RNAs (lncRNAs) have emerged as key regulators involved in lineage commitment and differentiation of stem cells, operating at various levels of gene regulation, including transcriptional, post-transcriptional, and post-translational processes. To gain deeper insights into the role of lncRNAs' in hASCs' differentiation, we conducted a comprehensive analysis of the lncRNA transcriptome (RNA-seq) and translatome (polysomal-RNA-seq) during a 24 h period of adipogenesis and osteogenesis. Our findings revealed distinct expression patterns between the transcriptome and translatome during both differentiation processes, highlighting 90 lncRNAs that are exclusively regulated in the polysomal fraction. These findings underscore the significance of investigating lncRNAs associated with ribosomes, considering their unique expression patterns and potential mechanisms of action, such as translational regulation and potential coding capacity for microproteins. Additionally, we identified specific lncRNA gene expression programs associated with adipogenesis and osteogenesis during the early stages of cell differentiation. By shedding light on the expression and potential functions of these polysome-associated lncRNAs, we aim to deepen our understanding of their involvement in the regulation of adipogenic and osteogenic differentiation, ultimately paving the way for novel therapeutic strategies and insights into regenerative medicine.

Bioinformatics analysis proposes a possible role for long noncoding RNA MIR17HG in retinoblastoma.

Retinoblastoma (RB) is the most common prevalent intraocular malignancy among infants and children, particularly in underdeveloped countries. With advancements in genomics and transcriptomics, noncoding RNAs have been increasingly utilized to investigate the molecular pathology of diverse diseases. This study aims to establish the competing endogenous RNAs network associated with RB, analyse the function of mRNAs and lncRNAs, and finds the relevant regulatory network. This study establishes a network of competing endogenous RNAs by Spearman correlation analysis and prediction based on RB patients and healthy children. Enrichment analyzes based on Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes are conducted to analyze the potential biological functions of lncRNA and mRNA networks. Weighted gene co-expression network analysis (WGCNA) is employed to identify gene cluster modules exhibiting the strongest correlation with RB. The results indicate a significant correlation between the lncRNA MIR17HG (R = .73, p = .02) and the RB phenotype. ceRNA networks reveal downstream miRNAs (hsa-mir-425-5p and hsa-mir455-5p) and mRNAs (MDM2, IPO11, and ITGA1) associated with MIR17Hg. As an inhibitor of the p53 signaling pathway, MDM2 can suppress the development of RB. In conclusion, lncRNAs play a role in RB, and the MIR17HG/hsa-mir-425-5p/MDM2 pathway may contribute to RB development by inhibiting the p53 signaling pathway.

Computational Methods for Functional Characterization of lncRNAS in Human Diseases: A Focus on Co-Expression Networks

Abstract: Treatment of many human diseases involves small-molecule drugs.Some target proteins, however, are not druggable with traditional strategies. Innovative RNA-targeted therapeutics may overcome such a challenge. Long noncoding RNAs (lncRNAs) are transcribed RNAs that do not translate into proteins. Their ability to interact with DNA, RNA, microRNAs (miRNAs), and proteins makes them an interesting target for regulating gene expression and signaling pathways.In the past decade, a catalog of lncRNAs has been studied in several human diseases. One of the challenges with lncRNA studies include their lack of coding potential, making, it difficult to characterize them in wet-lab experiments functionally. Several computational tools have thus been designed to characterize functions of lncRNAs centered around lncRNA interaction with proteins and RNA, especially miRNAs. This review comprehensively summarizes the methods and tools for lncRNA-RNA interactions and lncRNA-protein interaction prediction.We discuss the tools related to lncRNA interaction prediction using commonlyused models: ensemble-based, machine-learning-based, molecular-docking and network-based computational models. In biology, two or more genes co-expressed tend to have similar functions. Coexpression network analysis is, therefore, one of the most widely-used methods for understanding the function of lncRNAs. A major focus of our study is to compile literature related to the functional prediction of lncRNAs in human diseases using co-expression network analysis. In summary, this article provides relevant information on the use of appropriate computational tools for the functional characterization of lncRNAs that help wet-lab researchers design mechanistic and functional experiments.

Abstract A023: lncRNA-protein interactions that predict response to endocrine therapy in HR+ breast cancer

Abstract Hormone receptor positive (HR+) breast cancer (BCa) is the most frequently diagnosed BCa type accounting for 70% of all breast cancer cases. A large population of HR+ BCa patients (30-40%) are resistant to mainstay endocrine therapy and develop incurable metastatic disease. Hence, it is imperative to identify viable biomarkers that stratify patients as drug responders or non-responders. Emerging scientific literature highlights the essential role of long non-coding RNAs (lncRNA), a class of RNAs over 200 nucleotides in length that do not encode protein, in cancer drug resistance and metastatic transformation. Major biological functions of lncRNA rely on association with select protein interactors. As lncRNA equally bind proteins with and without canonical RNA-binding motifs, it is unclear what facilitates this lncRNA-protein interaction. Our recent studies show that SUMO post-translational modification (or SUMOylation) of target proteins potentiates binding with lncRNA, particularly at the chromatin. SUMOylation of heterochromatin protein 1 α (HP1α) drives interaction with multiple chromatin-associated lncRNA both within and outside canonical heterochromatin foci. Interaction with lncRNA supports SUMOylated HP1α’s unconventional function as a transcriptional repressor at select euchromatic loci. We now report an inverse relationship in which SUMOylated HP1α directs the stability of its lncRNA binding partner. Specifically, SUMO-modified HP1α directs cell-cycle dependent recruitment of the RNA degradation machinery to the chromatin and facilitates clearance of chromatin-bound lncRNA. This dynamic lncRNA degradation process is disturbed with cancer onset and instead favors aberrant cancer cell transformation. Consistently, restoring lncRNA degradation homeostasis decreases metastatic properties of HR+ BCa cells and increases sensitivity to targeted therapeutics currently in clinical trials. Our studies define a fundamental mechanism that dictates lncRNA stability and/or degradation in BCa cells. In addition, we present viable biomarkers that predict sensitivity to ET and alternative targeted therapies. Citation Format: Kacie D Waiters, Maram Quttina, Ashfia F Khan, Samaneh Karami, Anthony Peidl, Funmi Babajide, Tasneem Bawa-Khalfe. lncRNA-protein interactions that predict response to endocrine therapy in HR+ breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A023.

Preferential formation of Z-RNA over intercalated motifs in long noncoding RNA.

Secondary structure is a principal determinant of lncRNA function, predominantly regarding scaffold formation and interfaces with target molecules. Noncanonical secondary structures that form in nucleic acids have known roles in regulating gene expression and include G-quadruplexes (G4s), intercalated motifs (iMs), and R-loops (RLs). In this paper, we used the computational tools G4-iM Grinder and QmRLFS-finder to predict the formation of each of these structures throughout the lncRNA transcriptome in comparison to protein-coding transcripts. The importance of the predicted structures in lncRNAs in biological contexts was assessed by combining our results with publicly available lncRNA tissue expression data followed by pathway analysis. The formation of predicted G4 (pG4) and iM (piM) structures in select lncRNA sequences was confirmed in vitro using biophysical experiments under near-physiological conditions. We find that the majority of the tested pG4s form highly stable G4 structures, and identify many previously unreported G4s in biologically important lncRNAs. In contrast, none of the piM sequences are able to form iM structures, consistent with the idea that RNA is unable to form stable iMs. Unexpectedly, these C-rich sequences instead form Z-RNA structures, which have not been previously observed in regions containing cytosine repeats and represent an interesting and underexplored target for protein-RNA interactions. Our results highlight the prevalence and potential structure-associated functions of noncanonical secondary structures in lncRNAs, and show G4 and Z-RNA structure formation in many lncRNA sequences for the first time, furthering the understanding of the structure-function relationship in lncRNAs.

Recent Insights into the Angioregulatory Role of Long Non-coding RNAs and Circular RNAs in Gliomas: From Signaling Pathways to Clinical Aspects.

The most prevalent and severe malignancy of the central nervous system within the brain is glioma. Glioma is a vascularized cancer, and angiogenesis is necessary for glioma growth, invasion, and recurrence. It is also believed that this factor is this factor to be accountable for therapy resistance in many cancers, including glioma. The process of angiogenesis, which plays a crucial role in both health and disease situations such as cancer, involves the creation of new blood vessels from pre-existing ones. Non-coding RNAs (ncRNAs) are unique molecules that have been found to possess a wide range of abilities to modify the expression of various genes. They carry out their gene-modulating roles at a variety of distinct levels, including post-transcriptional and post-translational levels. Long ncRNAs (lncRNAs) and circular RNAs (circRNAs) are a group of ncRNA that have attracted particular attention and are involved in the angiogenesis mechanism in cancer. Understanding the regulatory mechanisms of these RNAs in the angiogenesis process in gliomas provides unique fundamental information about the process of tumor-associated neovascularization. On the other hand, due to developments in the characterisation of lncRNAs and circRNAs, these novel structures may potentially be used in clinics as possible biomarkers for treatment strategies that target tumor angiogenesis. Throughout the review, new knowledge and views about the angioregulatory function of circRNAs and lncRNAs in gliomas have been presented. Additionally, we talk about the novel idea of ncRNA-based therapeutics for gliomas in the future.

LncRNAs exhibit subtype-specific expression, survival associations, and cancer-promoting effects in breast cancer

Long non-coding RNAs (lncRNAs) play important roles in cancer progression, influencing processes such as invasion, metastasis, and drug resistance. Their reported cell type-dependent expression patterns suggest the potential for specialized functions in specific contexts. In breast cancer, lncRNA expression has been associated with different subtypes, highlighting their relevance in disease heterogeneity. However, our understanding of lncRNA function within breast cancer subtypes remains limited, warranting further investigation. We conducted a comprehensive analysis using the TANRIC dataset derived from the TCGA-BRCA cohort, profiling the expression, patient survival associations and immune cell type correlations of 12,727 lncRNAs across subtypes. Our findings revealed subtype-specific associations of lncRNAs with patient survival, tumor infiltrating lymphocytes and other immune cells. Targeting of lncRNAs exhibiting subtype-specific survival associations and expression in a panel of breast cancer cells demonstrated a selective reduction in cell proliferation within their associated subtype, supporting subtype-specific functions of certain lncRNAs. Characterization of HER2 + -specific lncRNA LINC01269 and TNBC-specific lncRNA AL078604.2 showed nuclear localization and altered expression of hundreds of genes enriched in cancer-promoting processes, including apoptosis, cell proliferation and immune cell regulation. This work emphasizes the importance of considering the heterogeneity of breast cancer subtypes and the need for subtype-specific analyses to fully uncover the relevance and potential impact of lncRNAs. Collectively, these findings demonstrate the contribution of lncRNAs to the distinct molecular, prognostic, and cellular composition of breast cancer subtypes.

Current perspectives of lncRNAs in abiotic and biotic stress tolerance in plants.

Abiotic/biotic stresses pose a major threat to agriculture and food security by impacting plant growth, productivity and quality. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long non-coding RNAs (lncRNAs) with sizes larger than 200 nucleotides in length, provides an important new perspective on the centrality of RNA in gene regulation. In plants, lncRNAs are widespread and fulfill multiple biological functions in stress response. In this paper, the research advances on the biological function of lncRNA in plant stress response were summarized, like as Natural Antisense Transcripts (NATs), Competing Endogenous RNAs (ceRNAs) and Chromatin Modification etc. And in plants, lncRNAs act as a key regulatory hub of several phytohormone pathways, integrating abscisic acid (ABA), jasmonate (JA), salicylic acid (SA) and redox signaling in response to many abiotic/biotic stresses. Moreover, conserved sequence motifs and structural motifs enriched within stress-responsive lncRNAs may also be responsible for the stress-responsive functions of lncRNAs, it will provide a new focus and strategy for lncRNA research. Taken together, we highlight the unique role of lncRNAs in integrating plant response to adverse environmental conditions with different aspects of plant growth and development. We envisage that an improved understanding of the mechanisms by which lncRNAs regulate plant stress response may further promote the development of unconventional approaches for breeding stress-resistant crops.

Deep Conservation and Unexpected Evolutionary History of Neighboring lncRNAs MALAT1 and NEAT1

Long non-coding RNAs (lncRNAs) have begun to receive overdue attention for their regulatory roles in gene expression and other cellular processes. Although most lncRNAs are lowly expressed and tissue-specific, notable exceptions include MALAT1 and its genomic neighbor NEAT1, two highly and ubiquitously expressed oncogenes with roles in transcriptional regulation and RNA splicing. Previous studies have suggested that NEAT1 is found only in mammals, while MALAT1 is present in all gnathostomes (jawed vertebrates) except birds. Here we show that these assertions are incomplete, likely due to the challenges associated with properly identifying these two lncRNAs. Using phylogenetic analysis and structure-aware annotation of publicly available genomic and RNA-seq coverage data, we show that NEAT1 is a common feature of tetrapod genomes except birds and squamates. Conversely, we identify MALAT1 in representative species of all major gnathostome clades, including birds. Our in-depth examination of MALAT1, NEAT1, and their genomic context in a wide range of vertebrate species allows us to reconstruct the series of events that led to the formation of the locus containing these genes in taxa from cartilaginous fish to mammals. This evolutionary history includes the independent loss of NEAT1 in birds and squamates, since NEAT1 is found in the closest living relatives of both clades (crocodilians and tuataras, respectively). These data clarify the origins and relationships of MALAT1 and NEAT1 and highlight an opportunity to study the change and continuity in lncRNA structure and function over deep evolutionary time.