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The pathogenesis of cardiovascular diseases (CVDs) is intricate, with liquid-liquid phase separation (LLPS) considered a crucial regulatory mechanism. Epigenetics is closely intertwined with cardiovascular diseases, involving mechanisms such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) that play pivotal roles in cardiovascular disease progression and regression. It is known that specific proteins and mRNAs associated with epigenetic modifications exhibit LLPS characteristics, influencing cardiovascular diseases. Consequently, targeting epigenetic modifications to modulate LLPS emerges as a promising strategy for cardiovascular diseases treatment. This review delves into the regulatory impact of liquid-liquid phase separation on cardiovascular diseases, with a specific focus on the epigenetic landscape. The current study sought to investigate the relationship between epigenetic landscape and phase separation in cardiovascular diseases development, as well as their therapeutic implications.

Plant memory plays an important role in the efficient and rapid acclimation to a swiftly changing environment. In addition, since plant memory can be inherited, it is also of adaptive and evolutionary importance. The ability of a plant to store, retain, retrieve and delete information on acquired experience is based on cellular, biochemical and molecular networks in the plants. This review offers an up-to-date overview on the formation, types, checkpoints of plant memory based on our current knowledge and focusing on its transcriptional aspects, the transcriptional memory. Roles of long and small non-coding RNAs are summarized in the regulation, formation and the cooperation between the different layers of the plant memory, i.e. in the establishment of epigenetic changes associated with memory formation in plants. The RNA interference mechanisms at the RNA and DNA level and the interplays between them are also presented. Furthermore, this review gives an insight of how exploitation of plant transcriptional memory may provide new opportunities for elaborating promising cost-efficient, and effective strategies to cope with the ever-changing environmental perturbations, caused by climate change. The potentials of plant memory-based methods, such as crop priming, cross acclimatization, memory modification by miRNAs and associative use of plant memory, in the future’s agriculture are also discussed.

Life expectancy in cancer patients has been extended in recent years, thanks to major breakthroughs in therapeutic developments. However, this also unmasked an increased incidence of cardiovascular diseases in cancer survivors, which is in part attributable to cancer therapy‐related cardiovascular toxicity. Non‐coding RNAs (ncRNAs) have received much appreciation due to their impact on gene expression. NcRNAs, which include microRNAs, long ncRNAs and circular RNAs, are non‐protein‐coding transcripts that are involved in the regulation of various biological processes, hence shaping cell identity and behaviour. They have also been implicated in disease development, including cardiovascular diseases, cancer and, more recently, cancer therapy‐associated cardiotoxicity. This review outlines key features of cancer therapy‐associated cardiotoxicity, what is known about the roles of ncRNAs in these processes and how ncRNAs could be exploited as therapeutic targets for cardioprotection. [ABSTRACT FROM AUTHOR]

Background: Unlike Transposable Elements (TEs) and gene/genome duplication, the role of the so-called nuclear plastid DNA sequences (NUPTs) in shaping the evolution of genome architecture and function remains poorly studied. We investigate here the functional and evolutionary fate of NUPTs in the orphan crop Moringa oleifera (moringa), featured by the highest fraction of plastid DNA found so far in any plant genome, focusing on (i) any potential biases in their distribution in relation to specific nuclear genomic features, (ii) their contribution to the emergence of new genes and gene regions, and (iii) their impact on the expression of target nuclear genes. Results: In agreement with their potential mutagenic effect, NUPTs are underrepresented among structural genes, although their overall transcription levels and broadness were only lower when involved exonic regions; the occurrence of plastid DNA generally did not result in a broader expression, except among those affected in introns by older NUPTs. In contrast, we found a strong enrichment of NUPTs among specific superfamilies of retrotransposons and several classes of RNA genes, including those participating in the protein biosynthetic machinery (i.e., rRNA and tRNA genes) and a specific class of regulatory RNAs. A significant fraction of NUPT RNA genes was found to be functionally expressed, thus potentially contributing to the nuclear pool. Conclusions: Our results complete our view of the molecular factors driving the evolution of nuclear genome architecture and function, and support plastid DNA in moringa as a major source of (i) genome complexity and (ii) the nuclear pool of RNA genes. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) and non-coding RNAs (ncRNAs) are emerging contributors to Alzheimer's disease (AD) pathophysiology. Differential abundance of ncRNAs carried by EVs may provide valuable insights into underlying disease mechanisms. Brain tissue-derived EVs (bdEVs) are particularly relevant, as they may offer valuable insights about the tissue of origin. However, there is limited research on diverse ncRNA species in bdEVs in AD. Objective: This study explored whether the non-coding RNA composition of EVs isolated from post-mortem brain tissue is related to AD pathogenesis. Methods: bdEVs from age-matched late-stage AD patients (n = 23) and controls (n = 10) that had been separated and characterized in our previous study were used for RNA extraction, small RNA sequencing, and qPCR verification. Results: Significant differences of non-coding RNAs between AD and controls were found, especially for miRNAs and tRNAs. AD pathology-related miRNA and tRNA differences of bdEVs partially matched expression differences in source brain tissues. AD pathology had a more prominent association than biological sex with bdEV miRNA and tRNA components in late-stage AD brains. Conclusions: Our study provides further evidence that EV non-coding RNAs from human brain tissue, including but not limited to miRNAs, may be altered and contribute to AD pathogenesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common form of dementia. There are two main types of AD: familial and sporadic. Familial AD is linked to mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2). On the other hand, sporadic AD is the more common form of the disease and has genetic, epigenetic, and environmental components that influence disease onset and progression. Investigating the epigenetic mechanisms associated with AD is essential for increasing understanding of pathology and identifying biomarkers for diagnosis and treatment. Chemical covalent modifications on DNA and RNA can epigenetically regulate gene expression at transcriptional and posttranscriptional levels and play protective or pathological roles in AD and other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

RNA methylation, the most prevalent type of RNA modification, encompasses more than 60 % of all known RNA modifications. With the advancement of methylation sequencing technologies, a diverse range of biological functions associated with RNA methylation in eukaryotes has been revealed. Specifically, 5-methylcytosine (m5C) modifications have been extensively observed in various RNA molecules, including messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and non-coding RNAs. These m5C modifications have been shown to impact critical RNA processes, such as mRNA translation, rRNA assembly, and tRNA stability. Notably, emerging evidence suggests that m5C modifications play significant roles in the initiation and progression of human cancers. However, a comprehensive understanding of the intricate m5C networks involved in human cancers is yet to be fully realized. In this comprehensive review, we provide an up-to-date summary of the roles and potential mechanisms underlying m5C modification in human cancers. [ABSTRACT FROM AUTHOR]

Summary: Despite the substantial progress in multiple myeloma (MM) therapy nowadays, treatment resistance and disease relapse remain major clinical hindrances. Herein, we have investigated tRNA‐derived fragment (tRF) profiles in MM and precursor stages (smoldering MM/sMM; monoclonal gammopathy of undetermined significance/MGUS), aiming to unveil potential MM‐related tRFs in ameliorating MM prognosis and risk stratification. Small RNA‐seq was performed to profile tRFs in bone marrow CD138+ plasma cells, revealing the significant deregulation of the mitochondrial internal tRFHisGTG (mt‐i‐tRFHisGTG) in MM versus sMM/MGUS. The screening cohort of the study consisted of 147 MM patients, and mt‐i‐tRFHisGTG levels were quantified by RT‐qPCR. Disease progression was assessed as clinical end‐point for survival analysis, while internal validation was performed by bootstrap and decision curve analyses. Screening cohort analysis highlighted the potent association of reduced mt‐i‐tRFHisGTG levels with patients' bone disease (p = 0.010), osteolysis (p = 0.023) and with significantly higher risk for short‐term disease progression following first‐line chemotherapy, independently of patients' clinical data (HR = 1.954; p = 0.036). Additionally, mt‐i‐tRFHisGTG‐fitted multivariate models led to superior risk stratification of MM patients' treatment outcome and prognosis compared to disease‐established markers. Notably, our study highlighted mt‐i‐tRFHisGTG loss as a powerful independent indicator of post‐treatment progression of MM patients, leading to superior risk stratification of patients' treatment outcome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

High mobility group AT-hook 2 (HMGA2) is a member of the non-histone chromosomal high mobility group (HMG) protein family, which participate in embryonic development and other biological processes. HMGA2 overexpression is associated with breast cancer (BC) cell growth, proliferation, metastasis, and drug resistance. Furthermore, HMGA2 expression is positively associated with poor prognosis of patients with BC, and inhibiting HMGA2 signaling can stimulate BC cell progression and metastasis. In this review, we focus on HMGA2 expression changes in BC tissues and multiple BC cell lines. Wnt/β-catenin, STAT3, CNN6, and TRAIL-R2 proteins are upstream mediators of HMGA2 that can induce BC invasion and metastasis. Moreover, microRNAs (miRNAs) can suppress BC cell growth, invasion, and metastasis by inhibiting HMGA2 expression. Furthermore, long noncoding RNAs (LncRNAs) and circular RNAs (CircRNAs) mainly regulate HMGA2 mRNA and protein expression levels by sponging miRNAs, thereby promoting BC development. Additionally, certain small molecule inhibitors can suppress BC drug resistance by reducing HMGA2 expression. Finally, we summarize findings demonstrating that HMGA2 siRNA and HMGA2 siRNA-loaded nanoliposomes can suppress BC progression and metastasis. [ABSTRACT FROM AUTHOR]

Bone homeostasis involves bone formation and resorption mediated by osteoblasts and osteoclasts. The integrity of bone tissue depends on the dynamic balance between the two. Studies have shown that the establishment of bone homeostasis is closely related to genetic factors, in addition to age, gender, and lifestyle. Epigenomics describes a genetic mechanism that controls gene expression without altering the DNA sequence, including DNA methylation, histone modification, and non-coding RNAs. Exercise, as an exogenous stimulus, influences disease progression by interfering with the epigenomic state of genes in a genetic-environmental context. This suggests that exercise serves as a bridge between macro- and micro-stimuli in the regulation of bone homeostasis. Based on this, this paper comprehensively reviews the detailed mechanism of epigenomic regulation of bone homeostasis, explores the potential pathways through which exercise interferes with epigenomic effects on bone homeostasis, and summarizes the complete framework of the genetic-environmental-skeletal interactions, which provides a new perspective for the regulation of bone homeostasis by exercise and the intervention of endogenous factors. [ABSTRACT FROM AUTHOR]

Non-coding RNAs (ncRNAs), which are incapable of encoding proteins, are involved in the progression of numerous tumors by altering transcriptional and post-transcriptional processing. Recent studies have revealed prominent features of ncRNAs in pyroptosis, a type of non-apoptotic programmed cellular destruction linked to an inflammatory reaction. Drug resistance has arisen gradually as a result of anti-apoptotic proteins, therefore strategies based on pyroptotic cell death have attracted increasing attention. We have observed that ncRNAs may exert significant influence on cancer therapy, chemotherapy, radio- therapy, targeted therapy and immunotherapy, by regulating pyroptosis. Literatures were searched (December 2023) for studies on cancer therapy for ncRNAs-mediated pyroptotic cell death. The most universal mechanical strategy for ncRNAs to regulate target genes is competitive endogenous RNAs (ceRNA). Besides, certain ncRNAs could directly interact with proteins and modulate downstream genes to induce pyroptosis, resulting in tumor growth or inhibition. In this review, we aim to display that ncRNAs, predominantly long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), could function as potential biomarkers for diagnosis and prognosis and produce new insights into anti-cancer strategies modulated by pyroptosis for clinical applications. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) ranks first among female malignant tumors and involves hormonal changes and genetic as well as environmental risk factors. In recent years, with the improvement of medical treatment, a variety of therapeutic approaches for breast cancer have emerged and have strengthened to accommodate molecular diversity. However, the primary way to improve the effective treatment of breast cancer patients is to overcome treatment resistance. Recent studies have provided insights into the mechanisms of resistance to exosome effects in BC. Exosomes are membrane-bound vesicles secreted by both healthy and malignant cells that facilitate intercellular communication. Specifically, exosomes released by tumor cells transport their contents to recipient cells, altering their properties and promoting oncogenic components, ultimately resulting in drug resistance. As important coordinators, non-coding RNAs (ncRNAs) are involved in this process and are aberrantly expressed in various human cancers. Exosome-derived ncRNAs, including microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as crucial components in understanding drug resistance in breast cancer. This review provides insights into the mechanism of exosome-derived ncRNAs in breast cancer drug resistance, thereby suggesting new strategies for the treatment of BC. [ABSTRACT FROM AUTHOR]

Cancer-related cachexia is a metabolic syndrome characterized by weight loss, adipose tissue decomposition, and progressive skeletal muscle atrophy. It is a major complication of many advanced cancers and seriously affects the quality of life and survival of cancer patients. However, the specific molecules that mediate cancer-related cachexia remain elusive, and the fundamental cellular and molecular mechanisms associated with muscle atrophy and lipidolysis in cancer patients still need to be investigated. Exosomes, a newly discovered class of small extracellular vesicles that facilitate intercellular communication, have a significant role in the onset and development of various cancers. Studies have shown that exosomes play a role in the onset and progression of cancer-related cachexia by transporting active molecules such as nucleic acids and proteins. This review aimed to provide an overview of exosome developments in cancer-induced skeletal muscle atrophy and adipose tissue degradation. More importantly, exosomes were shown to have potential as diagnostic markers or therapeutic strategies for cachexia and were prospected, providing novel strategies for the diagnosis and treatment of cancer-related cachexia. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) stands as a perplexing autoimmune disorder affecting the neuromuscular junction, driven by a multitude of antibodies targeting postsynaptic elements. However, the mystery of MG pathogenesis has yet to be completely uncovered, and its heterogeneity also challenges diagnosis and treatment. Growing evidence shows the differential expression of non-coding RNAs (ncRNAs) in MG has played an essential role in the development of MG in recent years. Remarkably, these aberrantly expressed ncRNAs exhibit distinct profiles within diverse clinical subgroups and among patients harboring various antibody types. Furthermore, they have been implicated in orchestrating the production of inflammatory cytokines, perturbing the equilibrium of T helper 1 cells (Th1), T helper 17 cells (Th17), and regulatory T cells (Tregs), and inciting B cells to generate antibodies. Studies have elucidated that certain ncRNAs mirror the clinical severity of MG, while others may hold therapeutic significance, showcasing a propensity to return to normal levels following appropriate treatments or potentially foretelling the responsiveness to immunosuppressive therapies. Notably, the intricate interplay among these ncRNAs does not follow a linear trajectory but rather assembles into a complex network, with competing endogenous RNA (ceRNA) emerging as a prominent hub in some cases. This comprehensive review consolidates the landscape of dysregulated ncRNAs in MG, briefly delineating their pivotal role in MG pathogenesis. Furthermore, it explores their promise as prospective biomarkers, aiding in the elucidation of disease subtypes, assessment of disease severity, monitoring therapeutic responses, and as novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a clinical syndrome that is one of the major causes of end-stage renal disease (ESRD). The pathogenesis of DKD is complex and multifaceted, with most studies indicating its association with genetics, advanced glycosylation end-product deposition, polyol pathway and protein C activation, lipid metabolism abnormalities, microcirculatory dysfunction, oxidative stress, inflammatory factors, and the kallikrein-kinin system. Epigenetics is the science studying gene expression regulation without changes in the DNA sequence. In recent years, increasing evidence has shown that epigenetic mechanisms play a crucial role in the initiation and progression of DKD. For instance, epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNAs can influence the expression of DKD-related genes, thereby regulating the development and progression of DKD. On the other hand, metabolic memory is an important concept in DKD research. Metabolic memory refers to the phenomenon where cells maintain a certain metabolic state even after the disappearance of metabolic stress factors. This state can influence cell function and fate. In DKD, metabolic stress factors such as hyperglycemia can lead to metabolic memory in renal cells, affecting their function and fate, ultimately leading to the development and progression of DKD. Therefore, to further explore the pathogenesis of DKD, research on epigenetics should be strengthened, aiming to provide new ideas and methods for the prevention and treatment of DKD. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma is a highly malignant tumor with increasing prevalence worldwide. Extracellular vesicles exert their biological functions via the delivery of different biomolecules, including non-coding RNAs. In this review, the diverse roles of the non-coding RNA cargo of hepatocellular carcinoma-derived extracellular vesicles will be discussed. Their function in tumor progression, immune escape, and drug resistance, as well as their potentialvalue as biomarkers of disease, will be summarized. Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is a major public health problem worldwide, and it is often diagnosed at advanced stages, when no effective treatment options are available. Extracellular vesicles (EVs) are nanosized double-layer lipid vesicles containing various biomolecule cargoes, such as lipids, proteins, and nucleic acids. EVs are released from nearly all types of cells and have been shown to play an important role in cell-to-cell communication. In recent years, many studies have investigated the role of EVs in cancer, including HCC. Emerging studies have shown that EVs play primary roles in the development and progression of cancer, modulating tumor growth and metastasis formation. Moreover, it has been observed that non-coding RNAs (ncRNAs) carried by tumor cell-derived EVs promote tumorigenesis, regulating the tumor microenvironment (TME) and playing critical roles in the progression, angiogenesis, metastasis, immune escape, and drug resistance of HCC. EV-related ncRNAs can provide information regarding disease status, thus encompassing a role as biomarkers. In this review, we discuss the main roles of ncRNAs present in HCC-derived EVs, including micro(mi) RNAs, long non-coding (lnc) RNAs, and circular (circ) RNAs, and their potential clinical value as biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: Optimal reproductive performance on goat farms is an important trait in terms of production and economics. From a genetic perspective, understanding molecular mechanisms through the use of RNA-seq technology can help us better understand goat herds. In this study, a whole-transcriptome sequencing approach was used to identify lncRNA, circRNA, miRNA, and mRNA expression in the ovaries of Chongming white goats in terms of high and low fecundity during the estrus phase. These results were helpful in terms of further studying the molecular mechanisms of goat reproduction. Reproductive performance is one of the most important economic traits in the goat industry. Increasing the number of goats is an effective measure to improve production efficiency and reduce production costs. Ovaries are important reproductive organs in female mammals that directly affect the estrous cycle and reproductive abilities. Understanding the complex transcription network of non-coding RNAs (lncRNAs, circRNAs, and miRNAs) and messenger RNA (mRNA) could lead to significant insights into the ovarian regulation of the reproductive processes of animals. However, the whole-transcriptome analysis of the non-coding RNAs and mRNA of the ovaries in Chongming white goats between high-fecundity (HP) and low-fecundity (LP) groups is limited. In this study, a whole-transcriptome sequencing approach was used to identify lncRNA, circRNA, miRNA, and mRNA expression in the ovaries of Chongming white goats during the estrus phase using RNA-Seq technology. More than 20,000 messenger RNAs (mRNAs), 10,000 long non-coding RNAs (lncRNAs), 3500 circular RNAs (circRNAs), and 1000 micro RNAs (miRNAs) were identified. A total of 1024 differential transcripts (724 mRNAs, 112 lncRNAs, 178 circRNAs, and 10 miRNAs) existing between the HP and the LP groups were revealed through a bioinformatics analysis. They were enriched in the prolactin signaling pathway, the Jak–STAT signaling pathway, and the GnRH signaling pathway, as well as various metabolic pathways. Differentially expressed mRNAs (such as LYPD6, VEGFA, NOS3, TNXB, and EPHA2) and miRNAs (such as miR-10a-5p) play key roles in the regulation of goat ovaries during the estrus phase. The enrichment of pathways related to reproduction, such as the Hippo, Hedgehog, PI3K–AKT, and MAPK signaling pathways, suggests that they might be involved in the prolificacy of goat ovaries. Overall, we identified several gene modules associated with goat fecundity and provided a basis for a molecular mechanism in the ovaries of Chongming white goats. [ABSTRACT FROM AUTHOR]

Non-coding RNAs have been described as crucial regulators of gene expression and guards of cellular homeostasis. Some recent papers focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which makes them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complexes. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that resembles a vault. Their sequence and structure are highly evolutionarily conserved and show many similarities in comparison with different species, but vault RNAs have various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy. [ABSTRACT FROM AUTHOR]

The use of non-coding RNAs (ncRNAs) as drug targets is being researched due to their discovery and their role in disease. Targeting ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), is an attractive approach for treating various diseases, such as cardiovascular disease and cancer. This seminar discusses the current status of ncRNAs as therapeutic targets in different pathological conditions. Regarding miRNA-based drugs, this approach has made significant progress in preclinical and clinical testing for cardiovascular diseases, where the limitations of conventional pharmacotherapy are evident. The challenges of miRNA-based drugs, including specificity, delivery, and tolerability, will be discussed. New approaches to improve their success will be explored. Furthermore, it extensively discusses the potential development of targeted therapies for cardiovascular disease. Finally, this document reports on the recent advances in identifying and characterizing microRNAs, manipulating them, and translating them into clinical applications. It also addresses the challenges and perspectives towards clinical application. [ABSTRACT FROM AUTHOR]

Over the past decade, there have been reports of short novel functional peptides (less than 100 aa in length) translated from so-called non-coding RNAs (ncRNAs) that have been characterized using mass spectrometry (MS) and large-scale proteomics studies. Therefore, understanding the bivalent functions of some ncRNAs as transcripts that encode both functional RNAs and short peptides, which we named ncPEPs, will deepen our understanding of biology and disease. In 2020, we published the first database of functional peptides translated from non-coding RNAs—FuncPEP. Herein, we have performed an update including the newly published ncPEPs from the last 3 years along with the categorization of host ncRNAs. FuncPEP v2.0 contains 152 functional ncPEPs, out of which 40 are novel entries. A PubMed search from August 2020 to July 2023 incorporating specific keywords was performed and screened for publications reporting validated functional peptides derived from ncRNAs. We did not observe a significant increase in newly discovered functional ncPEPs, but a steady increase. The novel identified ncPEPs included in the database were characterized by a wide array of molecular and physiological parameters (i.e., types of host ncRNA, species distribution, chromosomal density, distribution of ncRNA length, identification methods, molecular weight, and functional distribution across humans and other species). We consider that, despite the fact that MS can now easily identify ncPEPs, there still are important limitations in proving their functionality. [ABSTRACT FROM AUTHOR]

Historically, the Y chromosome has presented challenges to classical methodology and philosophy of understanding the differences between males and females. A genetic unsolved puzzle, the Y chromosome was the last chromosome to be fully sequenced. With the advent of the Human Genome Project came a realization that the human genome is more than just genes encoding proteins, and an entire universe of RNA was discovered. This dark matter of biology and the black box surrounding the Y chromosome have collided over the last few years, as increasing numbers of non-coding RNAs have been identified across the length of the Y chromosome, many of which have played significant roles in disease. In this review, we will uncover what is known about the connections between the Y chromosome and the non-coding RNA universe that originates from it, particularly as it relates to long non-coding RNAs, microRNAs and circular RNAs. [ABSTRACT FROM AUTHOR]

Non-coding ribonucleic acids (ncRNAs) have been recently shown to contribute to tumorigenesis by mediating changes in metabolism. ncRNAs act as key molecules in metabolic pathways regulation. The dysregulation of ncRNAs during cancer progression contributes to altered metabolic phenotypes leading to reprogrammed metabolism. Since ncRNAs affect different tumor processes by regulating mitochondrial dynamics and metabolism, in the future ncRNAs can be exploited in disease detection, diagnosis, treatment, and resistance. The purpose of this review is to highlight the role of ncRNAs in mitochondrial metabolic reprogramming and to relate their therapeutic potential in the management of genitourinary cancer. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer stands as the predominant malignant tumor in the urological system, presenting a significant challenge to public health and garnering extensive attention. Recently, with the deepening research into tumor molecular mechanisms, non-coding RNAs (ncRNAs) have emerged as potential biomarkers offering guidance for the diagnosis and prognosis of bladder cancer. However, the definitive role of ncRNAs in bladder cancer remains unclear. Hence, this study aims to elucidate the relevance and significance of ncRNAs through a Meta-analysis. Methods: A systematic meta-analysis was executed, including studies evaluating the diagnostic performance of ncRNAs and their associations with overall survival (OS) and disease-free survival (DFS). Key metrics such as hazard ratios, sensitivity, specificity, and diagnostic odds ratios were extracted and pooled from these studies. Potential publication bias was assessed using Deeks’ funnel plot, and the robustness of the results was ascertained through a sensitivity analysis. Results: Elevated ncRNA expression showed a positive correlation with improved OS, evidenced by a hazard ratio (HR) of 0.82 (95% CI: 0.66-0.96, P<0.001). Similarly, a significant association was observed between heightened ncRNA expression and DFS, with an HR of 0.86 (95% CI: 0.73-0.99, P<0.001). Diagnostic performance analysis across 17 articles yielded a pooled sensitivity of 0.76 and a specificity of 0.83. The diagnostic odds ratio was recorded at 2.71, with the area under the ROC curve (AUC) standing at 0.85. Conclusion: Exosome ncRNAs appear to possess potential significance in the diagnostic and prognostic discussions of bladder cancer. Their relationship with survival outcomes and diagnostic measures suggests a possible clinical utility. Comprehensive investigations are needed to fully determine their role in the ever-evolving landscape of bladder cancer management, especially within the framework of personalized medicine. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains a significant contributor to cancer-related mortality. Novel high-throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation. Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns. Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation. The hypomethylation of specific repetitive elements generates an epigenetic field effect early in tumorigenesis. Epstein–Barr virus (EBV) infection triggers DNA methylation by dysregulating DNA methyltransferases (DNMT) enzyme activity, while persistent Hp-EBV co-infection leads to aggressive tumor behavior. Distinct histone modifications are also responsible for oncogene upregulation and tumor-suppressor gene silencing in gastric carcinomas. While histone methylation and acetylation processes have been extensively studied, other less prevalent alterations contribute to the development and migration of gastric cancer via a complex network of interactions. Enzymes, such as Nicotinamide N-methyltransferase (NNMT), which is involved in tumor's metabolic reprogramming, interact with methyltransferases and modify gene expression. Non-coding RNA molecules, including long non-coding RNAs, circular RNAs, and miRNAs serve as epigenetic regulators contributing to GC development, metastasis, poor outcomes and therapy resistance. Serum RNA molecules hold the potential to serve as non-invasive biomarkers for diagnostic, prognostic or therapeutic applications. Gastric fluids represent a valuable source to identify potential biomarkers with diagnostic use in terms of liquid biopsy. Ongoing clinical trials are currently evaluating the efficacy of next-generation epigenetic drugs, displaying promising outcomes. Various approaches including multiple miRNA inhibitors or targeted nanoparticles carrying epigenetic drugs are being designed to enhance existing treatment efficacy and overcome treatment resistance. [ABSTRACT FROM AUTHOR]

Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and nonprogrammed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors. [ABSTRACT FROM AUTHOR]

Breast cancer is significantly influenced by endoplasmic reticulum (ER) stress, impacting both its initiation and progression. When cells experience an accumulation of misfolded or unfolded proteins, they activate the unfolded protein response (UPR) to restore cellular balance. In breast cancer, the UPR is frequently triggered due to challenging conditions within tumors. The UPR has a dual impact on breast cancer. On one hand, it can contribute to tumor growth by enhancing cell survival and resistance to programmed cell death in unfavorable environments. On the other hand, prolonged and severe ER stress can trigger cell death mechanisms, limiting tumor progression. Furthermore, ER stress has been linked to the regulation of non-coding RNAs (ncRNAs) in breast cancer cells. These ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play essential roles in cancer development by influencing gene expression and cellular processes. An improved understanding of how ER stress and ncRNAs interact in breast cancer can potentially lead to new treatment approaches. Modifying specific ncRNAs involved in the ER stress response might interfere with cancer cell survival and induce cell death. Additionally, focusing on UPR-associated proteins that interact with ncRNAs could offer novel therapeutic possibilities. Therefore, this review provides a concise overview of the interconnection between ER stress and ncRNAs in breast cancer, elucidating the nuanced effects of the UPR on cell fate and emphasizing the regulatory roles of ncRNAs in breast cancer progression. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is an end-stage of many cardiac diseases and one of the main causes of death worldwide. The current management of this disease remains suboptimal. The adult mammalian heart was considered a post-mitotic organ. However, several reports suggest that it may possess modest regenerative potential. Adult cardiac progenitor cells (CPCs), the main players in the cardiac regeneration, constitute, as it may seem, a heterogenous group of cells, which remain quiescent in physiological conditions and become activated after an injury, contributing to cardiomyocytes renewal. They can mediate their beneficial effects through direct differentiation into cardiac cells and activation of resident stem cells but majorly do so through paracrine release of factors. CPCs can secrete cytokines, chemokines, and growth factors as well as exosomes, rich in proteins, lipids and non-coding RNAs, such as miRNAs and YRNAs, which contribute to reparation of myocardium by promoting angiogenesis, cardioprotection, cardiomyogenesis, anti-fibrotic activity, and by immune modulation. Preclinical studies assessing cardiac progenitor cells and cardiac progenitor cells-derived exosomes on damaged myocardium show that administration of cardiac progenitor cells-derived exosomes can mimic effects of cell transplantation. Exosomes may become new promising therapeutic strategy for heart regeneration nevertheless there are still several limitations as to their use in the clinic. Key questions regarding their dosage, safety, specificity, pharmacokinetics, pharmacodynamics and route of administration remain outstanding. There are still gaps in the knowledge on basic biology of exosomes and filling them will bring as closer to translation into clinic. [ABSTRACT FROM AUTHOR]

In recent years, EVs have emerged as promising vehicles for coding and non-coding RNAs (ncRNAs), which have demonstrated remarkable potential as biomarkers for various diseases, including chronic liver diseases (CLDs). EVs are small, membrane-bound particles released by cells, carrying an arsenal of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA species, such as piRNAs, circRNAs, and tsRNAs. These ncRNAs act as key regulators of gene expression, splicing, and translation, providing a comprehensive molecular snapshot of the cells of origin. The non-invasive nature of EV sampling, typically via blood or serum collection, makes them highly attractive candidates for clinical biomarker applications. Moreover, EV-encapsulated ncRNAs offer unique advantages over traditional cell-free ncRNAs due to their enhanced stability within the EVs, hence allowing for their detection in circulation for extended periods and enabling more sensitive and reliable biomarker measurements. Numerous studies have investigated the potential of EV-enclosed ncRNAs as biomarkers for CLD. MiRNAs, in particular, have gained significant attention due to their ability to rapidly respond to changes in cellular stress and inflammation, hallmarks of CLD pathogenesis. Elevated levels of specific miRNAs have been consistently associated with various CLD subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis B and C. LncRNAs have also emerged as promising biomarkers for CLD. These transcripts are involved in a wide range of cellular processes, including liver regeneration, fibrosis, and cancer progression. Studies have shown that lncRNA expression profiles can distinguish between different CLD subtypes, providing valuable insights into disease progression and therapeutic response. Promising EV-enclosed ncRNA biomarkers for CLD included miR-122 (elevated levels of miR-122 are associated with MASLD progression and liver fibrosis), miR-21 (increased expression of miR-21 is linked to liver inflammation and fibrosis in CLD patients), miR-192 (elevated levels of miR-192 are associated with more advanced stages of CLD, including cirrhosis and HCC), LncRNA HOTAIR (increased HOTAIR expression is associated with MASLD progression and MASH development), and LncRNA H19 (dysregulation of H19 expression is linked to liver fibrosis and HCC progression). In the present review, we focus on the EV-enclosed ncRNAs as promising tools for the diagnosis and monitoring of CLD of various etiologies. [ABSTRACT FROM AUTHOR]

Neurological disorders are a major group of non-communicable diseases affecting quality of life. Non-Coding RNAs (ncRNAs) have an important role in the etiology of neurological disorders. In studies on the genesis of neurological diseases, aquaporin 4 (AQP4) expression and activity have both been linked to ncRNAs. The upregulation or downregulation of several ncRNAs leads to neurological disorder progression by targeting AQP4. The role of ncRNAs and AQP4 in neurological disorders is discussed in this review. [ABSTRACT FROM AUTHOR]

Simple Summary: The Colorado potato beetle is known for its ability to cause significant damage to potato crops worldwide. Unfortunately, this insect is also capable of developing substantial resistance against different compounds deployed to regulate its spread. A better understanding of the molecular basis underlying this resistance is key in order to develop novel strategies aimed at this potato pest. The goal of the current study was, thus, to characterize the expression of transcripts with likely relevance for insecticide resistance in Colorado potato beetles treated with two compounds of interest. Changes were observed for several transcripts in response to either low- or high-dose exposure, as well as for different time durations. The modulation of one transcript using RNAi was also associated with the increased susceptibility of insects treated with the insecticide cyantraniliprole. Overall, this information highlights potentially relevant targets for insecticide resistance in the Colorado potato beetle and reveals a transcript of interest for investigating further within the context of cyantraniliprole response in this pest. The Colorado potato beetle (Leptinotarsa decemlineata (Say)) can cause extensive damage to agricultural crops worldwide and is a significant insect pest. This insect is notorious for its ability to evade various strategies deployed to control its spread and is known for its relative ease in developing resistance against different insecticides. Various molecular levers are leveraged by L. decemlineata for this resistance to occur, and a complete picture of the genes involved in this process is lacking. While small non-coding RNAs, including miRNAs, are differentially expressed in insects exposed to insecticides, levels of transcript coding for proteins underlying their synthesis remain to be characterized fully. The overarching objective of this work aims to fill that gap by assessing the expression of such targets in L. decemlineata exposed to cyantraniliprole and thiamethoxam. The expression status of Ago1, Ago2, Ago3, Dcr2a, Dcr2b, Expo-5, Siwi-1 and Siwi-2 transcripts were quantified via qRT-PCR in adult L. decemlineata treated with low and high doses of these compounds for different lengths of time. Variation in Ago1 and Dcr2b expression was notably observed in L. decemlineata exposed to cyantraniliprole, while thiamethoxam exposure was associated with the modulation of Dcr2a and Siwi-1 transcript levels. The down-regulation of Ago1 expression in L. decemlineata using dsRNA, followed by cyantraniliprole treatment, was associated with a reduction in the survival of insects with reduced Ago1 transcript expression. Overall, this work presents the insecticide-mediated modulation of transcripts associated with small non-coding RNA processing and showcases Ago1 as a target to further investigate its relevance in cyantraniliprole response. [ABSTRACT FROM AUTHOR]

Retinal homeostasis, a tightly regulated process maintaining the functional integrity of the retina, is vital for visual function. Emerging research has unveiled the critical role of epigenetic regulation in controlling gene expression patterns during retinal development, maintenance, and response to mutational loads and injuries. Epigenetic switches, including DNA methylation, histone modifications, and non-coding RNAs, play pivotal roles in orchestrating retinal gene expression and cellular responses through various intracellular, extracellular, and environmental modulators. This review compiles the current knowledge on epigenetic switches in retinal homeostasis, providing a deeper understanding of their impact on retinal structural integrity and function and using them as potential targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is a disease in which the myocardium of the heart becomes asymmetrically thickened, malformed, disordered, and loses its normal structure and function. Recent studies have demonstrated the significant involvement of inflammatory responses in HCM. However, the precise role of immune-related long non-coding RNAs (lncRNAs) in the pathogenesis of HCM remains unclear. In this study, we performed a comprehensive analysis of immune-related lncRNAs in HCM. First, transcriptomic RNA-Seq data from both HCM patients and healthy individuals (GSE180313) were reanalyzed thoroughly. Key HCM-related modules were identified using weighted gene co-expression network analysis (WGCNA). A screening for immune-related lncRNAs was conducted within the key modules using immune-related mRNA co-expression analysis. Based on lncRNA–mRNA pairs that exhibit shared regulatory microRNAs (miRNAs), we constructed a competing endogenous RNA (ceRNA) network, comprising 9 lncRNAs and 17 mRNAs that were significantly correlated. Among the 26 lncRNA–mRNA pairs, only the MIR210HG–BPIFC pair was verified by another HCM dataset (GSE130036) and the isoprenaline (ISO)-induced HCM cell model. Furthermore, knockdown of MIR210HG increased the regulatory miRNAs and decreased the mRNA expression of BPIFC correspondingly in AC16 cells. Additionally, the analysis of immune cell infiltration indicated that the MIR210HG–BPIFC pair was potentially involved in the infiltration of naïve CD4+ T cells and CD8+ T cells. Together, our findings indicate that the decreased expression of the lncRNA–mRNA pair MIR210HG–BPIFC was significantly correlated with the pathogenesis of the disease and may be involved in the immune cell infiltration in the mechanism of HCM. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is the most aggressive and common type of cancer within the central nervous system (CNS). Despite the vast knowledge of its physiopathology and histology, its etiology at the molecular level has not been completely understood. Thus, attaining a cure has not been possible yet and it remains one of the deadliest types of cancer. Usually, GB is diagnosed when some symptoms have already been presented by the patient. This diagnosis is commonly based on a physical exam and imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI), together with or followed by a surgical biopsy. As these diagnostic procedures are very invasive and often result only in the confirmation of GB presence, it is necessary to develop less invasive diagnostic and prognostic tools that lead to earlier treatment to increase GB patients' quality of life. Therefore, blood-based biomarkers (BBBs) represent excellent candidates in this context. microRNAs (miRNAs) are small, non-coding RNAs that have been demonstrated to be very stable in almost all body fluids, including saliva, serum, plasma, urine, cerebrospinal fluid (CFS), semen, and breast milk. In addition, serum-circulating and exosome-contained miRNAs have been successfully used to better classify subtypes of cancer at the molecular level and make better choices regarding the best treatment for specific cases. Moreover, as miRNAs regulate multiple target genes and can also act as tumor suppressors and oncogenes, they are involved in the appearance, progression, and even chemoresistance of most tumors. Thus, in this review, we discuss how dysregulated miRNAs in GB can be used as early diagnosis and prognosis biomarkers as well as molecular markers to subclassify GB cases and provide more personalized treatments, which may have a better response against GB. In addition, we discuss the therapeutic potential of miRNAs, the current challenges to their clinical application, and future directions in the field. [ABSTRACT FROM AUTHOR]

After many decades, during which most molecular studies on the regulation of gene expression focused on transcriptional events, it was realized that post-transcriptional control was equally important in order to determine where and when specific proteins were to be synthesized. Translational regulation is of the most importance in the brain, where all the steps of mRNA maturation, transport to different regions of the cells and actual expression, in response to specific signals, constitute the molecular basis for neuronal plasticity and, as a consequence, for structural stabilization/modification of synapses; notably, these latter events are fundamental for the highest brain functions, such as learning and memory, and are characterized by long-term potentiation (LTP) of specific synapses. Here, we will discuss the molecular bases of these fundamental events by considering both the role of RNA-binding proteins (RBPs) and the effects of non-coding RNAs involved in controlling splicing, editing, stability and translation of mRNAs. Importantly, it has also been found that dysregulation of mRNA metabolism/localization is involved in many pathological conditions, arising either during brain development or in the adult nervous system. [ABSTRACT FROM AUTHOR]

Pre-messenger RNA molecules are back-spliced to create circular RNAs, which are non-coding RNA molecules. After a thorough investigation, it was discovered that these circRNAs have critical biological roles. CircRNAs have a variety of biological functions, including their ability to operate as microRNA sponges, interact with proteins to alter their stabilities and activities, and provide templates for the translation of proteins. Evidence supports a link between the emergence of numerous diseases, including various cancer types, and dysregulated circRNA expression. It is commonly known that a significant contributing element to cancer development is the disruption of numerous molecular pathways essential for preserving cellular and tissue homeostasis. The dysregulation of multiple biological processes is one of the hallmarks of cancer, and the molecular pathways linked to these processes are thought to be promising targets for therapeutic intervention. The biological and carcinogenic effects of circRNAs in the context of cancer are thoroughly reviewed in this article. Specifically, we highlight circRNAs' involvement in signal transduction pathways and their possible use as novel biomarkers for the early identification and prognosis of human cancer. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is a complicated molecular process that governs cellular shape and function changes throughout tissue development and embryogenesis. In addition, EMT contributes to the development and spread of tumors. Expanding and degrading the surrounding microenvironment, cells undergoing EMT move away from the main location. On the basis of the expression of fibroblast-specific protein-1 (FSP1), fibroblast growth factor (FGF), collagen, and smooth muscle actin (-SMA), the mesenchymal phenotype exhibited in fibroblasts is crucial for promoting EMT. While EMT is not entirely reliant on its regulators like ZEB1/2, Twist, and Snail proteins, investigation of upstream signaling (like EGF, TGF-β, Wnt) is required to get a more thorough understanding of tumor EMT. Throughout numerous cancers, connections between tumor epithelial and fibroblast cells that influence tumor growth have been found. The significance of cellular crosstalk stems from the fact that these events affect therapeutic response and disease prognosis. This study examines how classical EMT signals emanating from various cancer cells interfere to tumor metastasis, treatment resistance, and tumor recurrence. [ABSTRACT FROM AUTHOR]

Embryonic temperature has a lasting impact on muscle phenotype in vertebrates, involving complex molecular mechanisms that encompass both protein-coding and non-coding genes. Circular RNAs (circRNAs) are a class of regulatory RNAs that play important roles in various biological processes, but the effect of variable thermal conditions on the circRNA transcriptome and its long-term impact on muscle growth plasticity remains largely unexplored. To fill this knowledge gap, we performed a transcriptomic analysis of circRNAs in fast muscle of Nile tilapia (Oreochromis niloticus) subjected to different embryonic temperatures (24°C, 28°C and 32°C) and then reared at a common temperature (28°C) for 4 months. Nile tilapia embryos exhibited faster development and subsequently higher long-term growth at 32°C compared to those reared at 28°C and 24°C. Next-generation sequencing data revealed a total of 5,141 unique circRNAs across all temperature groups, of which 1,604, 1,531, and 1,169 circRNAs were exclusively found in the 24°C, 28°C and 32°C groups, respectively. Among them, circNexn exhibited a 1.7-fold (log2) upregulation in the 24°C group and a 1.3-fold (log2) upregulation in the 32°C group when compared to the 28°C group. Conversely, circTTN and circTTN_b were downregulated in the 24°C groups compared to their 28°C and 32°C counterparts. Furthermore, these differentially expressed circRNAs were found to have multiple interactions with myomiRs, highlighting their potential as promising candidates for further investigation in the context of muscle growth plasticity. Taken together, our findings provide new insights into the molecular mechanisms that may underlie muscle growth plasticity in response to thermal variation in fish, with important implications in the context of climate change, fisheries and aquaculture.

Lung cancer is the leading cause of death among malignant tumors in the world. High lung cancer mortality rate is due to most of patients diagnosed at advanced stage. The Liquid biopsy of lung cancer have received recent interest for early diagnosis. One of the components of liquid biopsy is the exosome. The exosome cargos non-coding-RNAs, especially long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). The lung cancer derived exosomal non-coding RNAs play the pivotal roles of lung cancer in carcinogenesis, diagnosis, therapy, drug resistance and prognosis of lung cancer. Given ceRNA (competitive endogenous RNA) mechanism, lncRNA or circRNA can act as ceRNA to compete to bind miRNAs and alter the expression of the targeted mRNA, contributing to the development and progression of lung cancer. The current research progress of the roles of the exosomal non-coding-RNAs and the interplay of ceRNAs and miRNAs in mediated lung cancer is illustrated in this article. Hence, we presented an experimentally validated lung cancer derived exosomal non-coding RNAs-regulated target gene axis from already existed evidence in lung cancer. Then LncRNA/circRNA-miRNA-mRNA axis may be a potential target for lung cancer treatment and has great potential in the diagnosis and prognosis of lung cancer.

The cell cycle comprises sequential events during which a cell duplicates its genome and divides it into two daughter cells. This process is tightly regulated to ensure that the daughter cell receives identical copied chromosomal DNA and that any errors in the DNA during replication are correctly repaired. Cyclins and their enzyme partners, cyclin-dependent kinases (CDKs), are critical regulators of G- to M-phase transitions during the cell cycle. Mitogenic signals induce the formation of the cyclin/CDK complexes, resulting in phosphorylation and activation of the CDKs. Once activated, cyclin/CDK complexes phosphorylate specific substrates that drive the cell cycle forward. The sequential activation and inactivation of cyclin-CDK complexes are tightly controlled by activating and inactivating phosphorylation events induced by cell-cycle proteins. The non-coding RNAs (ncRNAs), which do not code for proteins, regulate cell-cycle proteins at the transcriptional and translational levels, thereby controlling their expression at different cell-cycle phases. Deregulation of ncRNAs can cause abnormal expression patterns of cell-cycle-regulating proteins, resulting in abnormalities in cell-cycle regulation and cancer development. This review explores how ncRNA dysregulation can disrupt cell division balance and discusses potential therapeutic approaches targeting these ncRNAs to control cell-cycle events in cancer treatment.

Long non-coding RNAs (lncRNAs) are being studied in farm animals due to their association with traits of economic interest, such as fat deposition. Based on the analysis of perirenal fat transcriptomes, this research explored the relevance of these regulatory elements to fat deposition in suckling lambs. To that end, meta-analysis techniques have been implemented to efficiently characterize and detect differentially expressed transcripts from two different RNA-seq datasets, one including samples of two sheep breeds that differ in fat deposition features, Churra and Assaf (n = 14), and one generated from Assaf suckling lambs with different fat deposition levels (n = 8). The joint analysis of the 22 perirenal fat RNA-seq samples with the FEELnc software allowed the detection of 3953 novel lncRNAs. After the meta-analysis, 251 differentially expressed genes were identified, 21 of which were novel lncRNAs. Additionally, a co-expression analysis revealed that, in suckling lambs, lncRNAs may play a role in controlling angiogenesis and thermogenesis, processes highlighted in relation to high and low fat deposition levels, respectively. Overall, while providing information that could be applied for the improvement of suckling lamb carcass traits, this study offers insights into the biology of perirenal fat deposition regulation in mammals.

Exosomal microRNAs (miRNAs) have great potential in the fight against hepatocellular carcinoma (HCC), the fourth most common cause of cancer-related death worldwide. In this study, we explored the various applications of these small molecules while analyzing their complex roles in tumor development, metastasis, and changes in the tumor microenvironment. We also discussed the complex interactions that exist between exosomal miRNAs and other non-coding RNAs such as circular RNAs, and show how these interactions coordinate important biochemical pathways that propel the development of HCC. The possibility of targeting exosomal miRNAs for therapeutic intervention is paramount, even beyond their mechanistic significance. We also highlighted their growing potential as cutting-edge biomarkers that could lead to tailored treatment plans by enabling early identification, precise prognosis, and real-time treatment response monitoring. This thorough analysis revealed an intricate network of exosomal miRNAs lead to HCC progression. Finally, strategies for purification and isolation of exosomes and advanced biosensing techniques for detection of exosomal miRNAs are also discussed. Overall, this comprehensive review sheds light on the complex web of exosomal miRNAs in HCC, offering valuable insights for future advancements in diagnosis, prognosis, and ultimately, improved outcomes for patients battling this deadly disease.

The oxidative damage induced by oxidized low-density lipoprotein (ox-LDL) plays a pivotal role in the development of atherosclerosis. In this study, we investigated the protective effects of quercetin, a plant-derived flavonoid, against ox-LDL-induced damage in human umbilical vein endothelial cells (HUVECs) by mitigating oxidative stress. Our findings demonstrate that quercetin substantially enhances cell viability by attenuating oxidative stress induced by ox-LDL (the cell viability increased from 48 % to 89 %). Notably, this process is intricately regulated by the MALAT1/miR-494–3p/PTEN axis. In HUVECs exposed to ox-LDL, interventions such as knocking down MALAT1 or overexpressing miR-494–3p result in increased cell viability and reduced accumulation of reactive oxygen species (ROS), akin to the protective effect observed with quercetin pretreatment. Through further exploration using molecular biological technique, MALAT1 was confirmed to interact with miR-494–3p and serve as a competing endogenous RNA (ceRNA). These results, for the first time, underscore the involvement of the MALAT1/miR-494–3p/PTEN axis in quercetin's protective action against ox-LDL-induced oxidative stress. Our research provides compelling evidence supporting quercetin as a potential candidate for anti-atherosclerotic therapy. Furthermore, it offers fresh insights into the pathogenesis of atherosclerosis and potential strategies for intervention in this condition.

Abstract Breast cancer is one of the most common malignancies that pose a serious threat to women's health. Reprogramming of energy metabolism is a major feature of the malignant transformation of breast cancer. Compared to normal cells, tumor cells reprogram metabolic processes more efficiently, converting nutrient supplies into glucose, amino acid and lipid required for malignant proliferation and progression. Non-coding RNAs(ncRNAs) are a class of functional RNA molecules that are not translated into proteins but regulate the expression of target genes. NcRNAs have been demonstrated to be involved in various aspects of energy metabolism, including glycolysis, glutaminolysis, and fatty acid synthesis. This review focuses on the metabolic regulatory mechanisms and clinical applications of metabolism-regulating ncRNAs involved in breast cancer. We summarize the vital roles played by metabolism-regulating ncRNAs for endocrine therapy, targeted therapy, chemotherapy, immunotherapy, and radiotherapy resistance in breast cancer, as well as their potential as therapeutic targets and biomarkers. Difficulties and perspectives of current targeted metabolism and non-coding RNA therapeutic strategies are discussed.

A stroke is a medical emergency characterized by the sudden interruption of blood flow to the brain, leading to cell death from oxygen deprivation. As a leading cause of mortality and long-term disability worldwide, strokes present a growing socioeconomic challenge, exacerbated by demographic shifts and an increasing incidence in younger populations. Analyzing post-stroke conditions is essential for predicting recovery trajectories and guiding personalized treatments. The process is crucial for mitigating long-term cognitive deficits and improving the quality of life for stroke survivors and their families. Epigenetic mechanisms are emerging as key influencers, with four significant modulators—miRNAs, lncRNAs, DNA methylation, and histone modifications—being identified as central to modulating neuronal repair and regeneration. However, this is a lack of knowledge as to how major epigenetic signatures affect post-stroke recovery. The paper systematically reviews the capacity of miRNAs to fine-tune neuroprotective responses and the broader regulatory functions of lncRNAs. Additionally, we examine how shifts in DNA methylation patterns and histone modifications correlate with stroke outcomes, presenting a case for precise epigenetic therapies. In this review, we highlight that these modulators offer promising therapeutic targets for enhancing recovery and provide novel insights into stroke pathology and treatment. We also offer a comparative analysis of the four modulators and present the challenges and future perspectives for each one. The review sets forth a trajectory for future research, underscoring the development of novel epigenetic-based therapeutics as a groundbreaking approach to enhance post-stroke neurorehabilitation and improve patient prognoses.

Abstract Venous thromboembolism, which includes deep venous thrombosis (DVT) and pulmonary embolism, is the third most common vascular disease in the world and seriously threatens the lives of patients. Currently, the effect of conventional treatments on DVT is limited. Endothelial progenitor cells (EPCs) play an important role in the resolution and recanalization of DVT, but an unfavorable microenvironment reduces EPC function. Non-coding RNAs, especially long non-coding RNAs and microRNAs, play a crucial role in improving the biological function of EPCs. Non-coding RNAs have become clinical biomarkers of diseases and are expected to serve as new targets for disease intervention. A theoretical and experimental basis for the development of new methods for preventing and treating DVT in the clinic will be provided by studies on the role and molecular mechanism of non-coding RNAs regulating EPC function in the occurrence and development of DVT. To summarize, the characteristics of venous thrombosis, the regulatory role of EPCs in venous thrombosis, and the effect of non-coding RNAs regulating EPCs on venous thrombosis are reviewed. This summary serves as a useful reference and theoretical basis for research into the diagnosis, prevention, treatment, and prognosis of venous thrombosis.

DNA from organelles called mitochondria is not inherited from the father. But mitochondrial RNAs that sense paternal diet and mitochondrial quality are delivered from sperm to egg, affecting offspring metabolism.Small mitochondrial RNAs in sperm sense paternal obesity. [ABSTRACT FROM AUTHOR]