Prognostic significance of CHCHD2P9 and ZNF204P in breast cancer: exploring their expression patterns and associations with malignancy-related genes.

BACKGROUND: Non-coding RNAs (ncRNAs) have a crucial impact on diverse cellular processes, influencing the progression of breast cancer (BC). The objective of this study was to identify novel ncRNAs in BC with potential effects on patient survival and disease progression. METHODS: We utilized the cancer genome atlas data to identify ncRNAs associated with BC pathogenesis. We explored the association between these ncRNA expressions and survival rates. A risk model was developed using candidate ncRNA expression and beta coefficients obtained from a multivariate Cox regression analysis. Co-expression networks were constructed to determine potential relationships between these ncRNAs and molecular pathways. For validation, we employed BC samples and the RT-qPCR method. RESULTS: Our findings revealed a noteworthy increase in the expression of AC093850.2 and CHCHD2P9 in BC, which was correlated with a poor prognosis. In contrast, ADAMTS9-AS1 and ZNF204P displayed significant downregulation and were associated with a favorable prognosis. The risk model, incorporating these four ncRNAs, robustly predicted patient survival. The co-expression network showed an effective association between levels of AC093850.2, CHCHD2P9, ADAMTS9-AS1, and ZNF204P and genes involved in pathways like metastasis, angiogenesis, metabolism, and DNA repair. The RT-qPCR results verified notable alterations in the expression of CHCHD2P9 and ZNF204P in BC samples. Pan-cancer analyses revealed alterations in the expression of these two ncRNAs across various cancer types. CONCLUSION: This study presents a groundbreaking discovery, highlighting the substantial dysregulation of CHCHD2P9 and ZNF204P in BC and other cancers, with implications for patient survival.

Recent advances in the reciprocal regulation of m6A modification with non-coding RNAs and its therapeutic application in acute myeloid leukemia.

N6-methyladenosine (m6A) is one of the most common modifications of RNA in eukaryotic cells and is involved in mRNA metabolism, including stability, translation, maturation, splicing, and export. m6A also participates in the modification of multiple types of non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, thereby affecting their metabolism and functions. Increasing evidence has revealed that m6A regulators, such as writers, erasers, and readers, perform m6A-dependent modification of ncRNAs, thus affecting cancer progression. Moreover, ncRNAs modulate m6A regulators to affect cancer development and progression. In this review, we summarize recent advances in understanding m6A modification and ncRNAs and provide insights into the interaction between m6A modification and ncRNAs in cancer. We also discuss the potential clinical applications of the mechanisms underlying the interplay between m6A modifications and ncRNAs in acute myeloid leukemia (AML). Therefore, clarifying the mutual regulation between m6A modifications and ncRNAs is of great significance to identify novel therapeutic targets for AML and has great clinical application prospects.

A candidate sex determination locus in amphibians which evolved by structural variation between X- and Y-chromosomes.

Most vertebrates develop distinct females and males, where sex is determined by repeatedly evolved environmental or genetic triggers. Undifferentiated sex chromosomes and large genomes have caused major knowledge gaps in amphibians. Only a single master sex-determining gene, the dmrt1-paralogue (dm-w) of female-heterogametic clawed frogs (Xenopus; ZW♀/ZZ♂), is known across >8740 species of amphibians. In this study, by combining chromosome-scale female and male genomes of a non-model amphibian, the European green toad, Bufo(tes) viridis, with ddRAD- and whole genome pool-sequencing, we reveal a candidate master locus, governing a male-heterogametic system (XX♀/XY♂). Targeted sequencing across multiple taxa uncovered structural X/Y-variation in the 5'-regulatory region of the gene bod1l, where a Y-specific non-coding RNA (ncRNA-Y), only expressed in males, suggests that this locus initiates sex-specific differentiation. Developmental transcriptomes and RNA in-situ hybridization show timely and spatially relevant sex-specific ncRNA-Y and bod1l-gene expression in primordial gonads. This coincided with differential H3K4me-methylation in pre-granulosa/pre-Sertoli cells, pointing to a specific mechanism of amphibian sex determination.

Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy.

BACKGROUND: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. METHODS: To identify DMRs, we employed the bump hunter method in samples from young (9-16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28-33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. RESULTS: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity. CONCLUSIONS: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.

Evolutionary Structure Conservation and Covariance Scores.

Effective homology search for non-coding RNAs is frequently not possible via sequence similarity alone. Current methods leverage evolutionary information like structure conservation or covariance scores to identify homologs in organisms that are phylogenetically more distant. In this chapter, we introduce the theoretical background of evolutionary structure conservation and covariance score, and we show hands-on how current methods in the field are applied on example datasets.

Senataxin deficiency disrupts proteostasis through nucleolar ncRNA-driven protein aggregation.

Senataxin is an evolutionarily conserved RNA-DNA helicase involved in DNA repair and transcription termination that is associated with human neurodegenerative disorders. Here, we investigated whether Senataxin loss affects protein homeostasis based on previous work showing R-loop-driven accumulation of DNA damage and protein aggregates in human cells. We find that Senataxin loss results in the accumulation of insoluble proteins, including many factors known to be prone to aggregation in neurodegenerative disorders. These aggregates are located primarily in the nucleolus and are promoted by upregulation of non-coding RNAs expressed from the intergenic spacer region of ribosomal DNA. We also map sites of R-loop accumulation in human cells lacking Senataxin and find higher RNA-DNA hybrids within the ribosomal DNA, peri-centromeric regions, and other intergenic sites but not at annotated protein-coding genes. These findings indicate that Senataxin loss affects the solubility of the proteome through the regulation of transcription-dependent lesions in the nucleus and the nucleolus.

Molecular and Therapeutic Roles of Non-Coding RNAs in Oral Cancer-A Review.

Oral cancer (OC) is among the most common malignancies in the world. Despite advances in therapy, the worst-case scenario for OC remains metastasis, with a 50% survival rate. Therefore, it is critical to comprehend the pathophysiology of the condition and to create diagnostic and treatment plans for OC. The development of high-throughput genome sequencing has revealed that over 90% of the human genome encodes non-coding transcripts, or transcripts that do not code for any proteins. This paper describes the function of these different kinds of non-coding RNAs (ncRNAs) in OC as well as their intriguing therapeutic potential. The onset and development of OC, as well as treatment resistance, are linked to dysregulated ncRNA expression. These ncRNAs' potentially significant roles in diagnosis and prognosis have been suggested by their differing expression in blood or saliva. We have outlined every promising feature of ncRNAs in the treatment of OC in this study.

[Research progress of the role of non-coding RNA in hyperoxia-induced acute lung injury].

Hyperoxia-induced acute lung injury (HALI) is an important complication of clinical oxygen therapy, which is mainly characterized by acute respiratory distress syndrome (ARDS) in adults and broncho-pulmonary dysplasia (BPD) in infants. HALI seriously affects the prognosis and quality of life of patients, so it has received more and more attention. However, the pathogenesis of HALI is complex and unclear, and there is no clear treatment method at present. Non-coding RNA (ncRNA) is an important type of functional RNA transcriptome. Due to the lack of effective open reading frame, ncRNA does not have the function of coding proteins. However, ncRNA can still regulate gene expression at multiple levels and affect the occurrence and development of many diseases. In recent years, a large number of in vitro and in vivo studies have shown that ncRNA is involved in the pathogenesis of HALI and is of great significance. This article reviews the expression and significance of ncRNA in HALI, in order to provide new diagnosis and treatment ideas for the prevention and treatment of HALI.

Comparative RNA Genomics.

Over the last quarter of a century it has become clear that RNA is much more than just a boring intermediate in protein expression. Ancient RNAs still appear in the core information metabolism and comprise a surprisingly large component in bacterial gene regulation. A common theme with these types of mostly small RNAs is their reliance of conserved secondary structures. Large-scale sequencing projects, on the other hand, have profoundly changed our understanding of eukaryotic genomes. Pervasively transcribed, they give rise to a plethora of large and evolutionarily extremely flexible non-coding RNAs that exert a vastly diverse array of molecule functions. In this chapter we provide a-necessarily incomplete-overview of the current state of comparative analysis of non-coding RNAs, emphasizing computational approaches as a means to gain a global picture of the modern RNA world.

Deciphering the Epigenetic Symphony of Cancer: Insights and Epigenetic Therapies Implications.

Epigenetic machinery is a cornerstone in normal cell development, orchestrating tissue-specific gene expression in mammalian cells. Aberrations in this intricate landscape drive substantial changes in gene function, emerging as a linchpin in cancer etiology and progression. While cancer was conventionally perceived as solely a genetic disorder, its contemporary definition encompasses genetic alterations intertwined with disruptive epigenetic abnormalities. This review explores the profound impact of DNA methylation, histone modifications, and noncoding RNAs on fundamental cellular processes. When these pivotal epigenetic mechanisms undergo disruption, they intricately guide the acquisition of the 6 hallmark characteristics of cancer within seemingly normal cells. Leveraging the latest advancements in decoding these epigenetic intricacies holds immense promise, heralding a new era in developing targeted and more efficacious treatment modalities against cancers driven by aberrant epigenetic modifications.

Noncoding RNAs in regulation of plant secondary metabolism.

Plant secondary metabolites (PSMs) are a large class of structurally diverse molecules, mainly consisting of terpenoids, phenolic compounds, and nitrogen-containing compounds, which play active roles in plant development and stress responses. The biosynthetic processes of PSMs are governed by a sophisticated regulatory network at multiple levels. Noncoding RNAs (ncRNAs) such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) may serve as post-transcriptional regulators for plant secondary metabolism through acting on genes encoding either transcription factors or participating enzymes in relevant metabolic pathways. High-throughput sequencing technologies have facilitated the large-scale identifications of ncRNAs potentially involved in plant secondary metabolism in model plant species as well as certain species with enriched production of specific types of PSMs. Moreover, a series of miRNA-target modules have been functionally characterized to be responsible for regulating PSM biosynthesis and accumulation in plants under abiotic or biotic stresses. In this review, we will provide an overview of current findings on the ncRNA-mediated regulation of plant secondary metabolism with special attention to its participation in plant stress responses, and discuss possible issues to be addressed in future fundamental research and breeding practice.

Role of melatonin in carcinogenesis and metastasis: From mechanistic insights to intermeshed networks of noncoding RNAs.

In recent years, seminal studies have been devoted to unraveling the puzzling mysteries associated with the cancer preventive/inhibitory role of melatonin. Our current knowledge of the translational mechanisms and the detailed structural insights have highlighted the characteristically exclusive role of melatonin in the inhibition of carcinogenesis and metastatic dissemination. This mini-review outlines recent discoveries related to mechanistic role of melatonin in prevention of carcinogenesis and metastasis. Moreover, another exciting facet of this mini-review is related to phenomenal breakthroughs linked with regulation of noncoding RNAs by melatonin in wide variety of cancers.

Competing endogenous RNA networks and ferroptosis in cancer: novel therapeutic targets.

As a newly identified regulated cell death, ferroptosis is a metabolically driven process that relies on iron and is associated with polyunsaturated fatty acyl peroxidation, elevated levels of reactive oxygen species (ROS), and mitochondrial damage. This distinct regulated cell death is dysregulated in various cancers; activating ferroptosis in malignant cells increases cancer immunotherapy and chemoradiotherapy responses across different malignancies. Over the last decade, accumulating research has provided evidence of cross-talk between non-coding RNAs (ncRNAs) and competing endogenous RNA (ceRNA) networks and highlighted their significance in developing and progressing malignancies. Aside from pharmaceutical agents to regulate ferroptosis, recent studies have shed light on the potential of restoring dysregulated ferroptosis-related ceRNA networks in cancer treatment. The present study provides a comprehensive and up-to-date review of the ferroptosis significance, ferroptosis pathways, the role of ferroptosis in cancer immunotherapy and chemoradiotherapy, ceRNA biogenesis, and ferroptosis-regulating ceRNA networks in different cancers. The provided insights can offer the authorship with state-of-the-art findings and future perspectives regarding the ferroptosis and ferroptosis-related ceRNA networks and their implication in the treatment and determining the prognosis of affected patients.

The mechanistic view of non-coding RNAs as a regulator of inflammatory pathogenesis of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. Emerging evidence suggests that inflammation plays a crucial role in the pathogenesis of PD, with the NLRP3 inflammasome implicated as a key mediator. Nfon-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have recently garnered attention for their regulatory roles in various biological processes, including inflammation. This review aims to provide a mechanistic insight into how ncRNAs function as regulators of inflammatory pathways in PD, with a specific focus on the NLRP3 inflammasome. We discuss the dysregulation of miRNAs and lncRNAs in PD pathogenesis and their impact on neuroinflammation through modulation of NLRP3 activation, cytokine production, and microglial activation. Additionally, we explore the crosstalk between ncRNAs, alpha-synuclein pathology, and mitochondrial dysfunction, further elucidating the intricate network underlying PD-associated inflammation. Understanding the mechanistic roles of ncRNAs in regulating inflammatory pathways may offer novel therapeutic targets for the treatment of PD and provide insights into the broader implications of ncRNA-mediated regulation in neuroinflammatory diseases.

Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis.

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.

From oncogenes to tumor suppressors: The dual role of ncRNAs in fibrosarcoma.

Fibrosarcoma is a challenging cancer originating from fibrous tissues, marked by aggressive growth and limited treatment options. The discovery of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs), has opened new pathways for understanding and treating this malignancy. These ncRNAs play crucial roles in gene regulation, cellular processes, and the tumor microenvironment. This review aims to explore the impact of ncRNAs on fibrosarcoma's pathogenesis, progression, and resistance to treatment, focusing on their mechanistic roles and therapeutic potential. A comprehensive review of literature from databases like PubMed and Google Scholar was conducted, focusing on the dysregulation of ncRNAs in fibrosarcoma, their contribution to tumor growth, metastasis, drug resistance, and their cellular pathway interactions. NcRNAs significantly influence fibrosarcoma, affecting cell proliferation, apoptosis, invasion, and angiogenesis. Their function as oncogenes or tumor suppressors makes them promising biomarkers and therapeutic targets. Understanding their interaction with the tumor microenvironment is essential for developing more effective treatments for fibrosarcoma. Targeting ncRNAs emerges as a promising strategy for fibrosarcoma therapy, offering hope to overcome the shortcomings of existing treatments. Further investigation is needed to clarify specific ncRNAs' roles in fibrosarcoma and to develop ncRNA-based therapies, highlighting the significance of ncRNAs in improving patient outcomes in this challenging cancer.

Key interactions of RNA polymerase with 6S RNA and secondary channel factors during pRNA synthesis.

Small non-coding 6S RNA mimics DNA promoters and binds to the σ70 holoenzyme of bacterial RNA polymerase (RNAP) to suppress transcription of various genes mainly during the stationary phase of cell growth or starvation. This inhibition can be relieved upon synthesis of short product RNA (pRNA) performed by RNAP from the 6S RNA template. Here, we have shown that pRNA synthesis depends on specific contacts of 6S RNA with RNAP and interactions of the σ finger with the RNA template in the active site of RNAP, and is also modulated by the secondary channel factors. We have adapted a molecular beacon assay with fluorescently labeled σ70 to analyze 6S RNA release during pRNA synthesis. We found the kinetics of 6S RNA release to be oppositely affected by mutations in the σ finger and in the CRE pocket of core RNAP, similarly to the reported role of these regions in promoter-dependent transcription. Secondary channel factors, DksA and GreB, inhibit pRNA synthesis and 6S RNA release from RNAP, suggesting that they may contribute to the 6S RNA-mediated switch in transcription during stringent response. Our results demonstrate that pRNA synthesis depends on a similar set of contacts between RNAP and 6S RNA as in the case of promoter-dependent transcription initiation and reveal that both processes can be regulated by universal transcription factors acting on RNAP.

Autophagy-associated non-coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis.

BACKGROUND: Parkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy-a crucial cellular process for maintaining protein and organelle integrity. METHODS: This review focuses on the role of non-coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples. RESULTS: Findings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes. CONCLUSION: ncRNAs hold significant therapeutic potential for addressing autophagy-related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy-related ncRNAs and discusses the challenges and prospective directions for developing ncRNA-based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches.

Sarcopenia as a Risk Factor for Alzheimer's Disease: Genetic and Epigenetic Perspectives.

Sarcopenia, defined as the age-associated loss of muscle mass and increased fragility with age, is increasing worldwide. The condition often precedes the development of Alzheimer's disease, thereby decreasing the levels of mobility and physical activity in those affected. Indeed, the loss of muscle mass has, in some studies, been associated with an increased risk of Alzheimer's disease and other dementias. However, a detailed understanding of the interplay between both conditions is not available and needs to be thoroughly addressed. In the following review, we focus on several genes, specifically APOE, BDNF, ACE, FTO, and FNDC5, that have been associated with both conditions. We also discuss the epigenetic regulation of each of these genes along with non-coding RNAs (ncRNAs) that may have a role in the development of both the sarcopenic and Alzheimer's disease phenotypes. Finally, we assert that the application of systems biology will unravel the relationship between sarcopenia and Alzheimer's disease and believe that the prevention of muscle loss in older age will reduce the incidence of debilitating cognitive decline.

Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus.

In recent years, the function of noncoding RNAs (ncRNAs) as regulatory molecules of cell physiology has begun to be better understood. Advances in viral molecular biology have shown that host ncRNAs, cellular factors, and virus-derived ncRNAs and their interplay are strongly disturbed during viral infections. Nevertheless, the folding of RNA virus genomes has also been identified as a critical factor in regulating canonical and non-canonical functions. Due to the influence of host ncRNAs and the structure of RNA viral genomes, complex molecular and cellular processes in infections are modulated. We propose three main categories to organize the current information about RNA-RNA interactions in some well-known human viruses. The first category shows examples of host ncRNAs associated with the immune response triggered in viral infections. Even though miRNAs introduce a standpoint, they are briefly presented to keep researchers moving forward in uncovering other RNAs. The second category outlines interactions between virus-host ncRNAs, while the third describes how the structure of the RNA viral genome serves as a scaffold for processing virus-derived RNAs. Our grouping may provide a comprehensive framework to classify ncRNA-host-cell interactions for emerging viruses and diseases. In this sense, we introduced them to organize DENV-host-cell interactions.