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Schizophrenia (SCZ) is a complex, heritable and polygenic neuropsychiatric disease, which disables the patients as well as decreases their life expectancy and quality of life. Common and rare variants studies on SCZ subjects have provided >100 genomic loci that hold importance in the context of SCZ pathophysiology. Transcriptomic studies from clinical samples have informed about the differentially expressed genes (DEGs) and non-coding RNAs in SCZ patients. Despite these advancements, no causative genes for SCZ were found and hence SCZ is difficult to recapitulate in animal models. In the last decade, induced Pluripotent Stem Cells (iPSCs)-based models have helped in understanding the neural phenotypes of SCZ by studying patient iPSC-derived 2D neuronal cultures and 3D brain organoids. Here, we have aimed to provide a simplistic overview of the current progress and advancements after synthesizing the enormous literature on SCZ genetics and SCZ iPSC-based models. Although further understanding of SCZ genetics and pathophysiological mechanisms using these technological advancements is required, the recent approaches have allowed to delineate important cellular mechanisms and biological pathways affected in SCZ. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) accounts for about 13% of all pediatric cancer mortality and is the leading cause of pediatric cancer death for children aged 1 to 5 years. NB, a developmental malignancy of neural ganglia, originates from neural crest-derived cells, which undergo a defective sympathetic neuronal differentiation due to genomic and epigenetic aberrations. NB is a complex disease with remarkable biological and genetic variation and clinical heterogeneity, such as spontaneous regression, treatment resistance, and poor survival rates. Depending on its severity, NB is categorized as high-risk, intermediate-risk, and low-risk., whereas high-risk NB accounts for a high infant mortality rate. Several studies revealed that NB cells suppress immune cell activity through diverse signaling pathways, including exosome-based signaling pathways. Exosome signaling has been shown to modulate gene expression in the target immune cells and attenuate the signaling events through non-coding RNAs. Since high-risk NB is characterized by a low survival rate and high clinical heterogeneity with current intensive therapies, it is crucial to unravel the molecular events of pathogenesis and develop novel therapeutic targets in high-risk, relapsed, or recurrent tumors in NB to improve patient survival. This article discusses etiology, pathophysiology, risk assessment, molecular cytogenetics, and the contribution of extracellular vesicles, non-coding RNAs, and cancer stem cells in the tumorigenesis of NB. We also detail the latest developments in NB immunotherapy and nanoparticle-mediated drug delivery treatment options. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite recent advances in epithelial ovarian cancer (EOC) management, the highly heterogenous histological/molecular tumour background and patients' treatment response obstructs personalised prognosis and therapeutics. Herein, we have studied the role and clinical utility of the novel subclass of tRNA-derived small RNA fragments emerging via 3′-trailer processing of pre-tRNAs (3′U-tRFs) in EOC. SK-OV-3 and OVCAR-3 cells were used for in vitro study. Following transfection, cell growth and migration were assessed by CCK8 and wound healing assays, respectively. 3′U-tRFs levels were assessed by reverse transcription quantitative PCR (RT-qPCR), following 3′-end RNA polyadenylation. A screening (OVCAD, n = 100) and institutionally independent validation (TU Munich, n = 103) cohorts were employed for survival analysis using disease progression and patients' death as clinical end-points. Bootstrap analysis was performed for internal validation, and decision curve analysis was used to evaluate clinical benefit on disease prognosis. Following primary clinical assessment, target prediction and gene ontology analyses, the 3′U-tRFValCAC (derived from pre-tRNAValCAC) was highlighted to regulate cell proliferation and adhesion, and to correlate with inferior patients' outcome. 3′U-tRFValCAC transfection of SK-OV-3 and OVCAR-3 cells resulted in significantly increased cell growth and migration, in a dose-dependent manner. Elevated tumour 3′U-tRFValCAC levels were associated with significantly higher risk for early progression and worse survival following first-line platinum-based chemotherapy, independently of patients' clinicopathological data, chemotherapy response, and residual tumour. Interestingly, 3′U-tRFValCAC-fitted multivariate models improved risk stratification and provided superior clinical net benefit in prediction of treatment outcome compared to disease established markers. 3′U-tRFValCAC promotes tumour cell growth and migration and supports modern risk stratification and prognosis in EOC. • 3′U-tRFValCAC enhances cell growth and migration of ovarian cancer cells. • Patients with elevated 3′U-tRFValCAC are at higher risk for early progression. • 3′U-tRFValCAC is significantly associated with poor overall survival in ovarian cancer. • 3′U-tRFValCAC-fitted multivariate models improved risk stratification and prognosis. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH) regulates the expression of bone remodeling genes by enhancing the activity of Runx2 in osteoblasts. p300, a histone acetyltransferase, acetylated Runx2 to activate the expression of its target genes. PTH stimulated the expression of p300 in rat osteoblastic cells. Increasing studies suggested the potential of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and circular RNAs (circRNAs), in regulating gene expression under both physiological and pathological conditions. In this study, we hypothesized that PTH regulates Runx2 activity via ncRNAs-mediated p300 expression in rat osteoblastic cells. Bioinformatics and experimental approaches identified PTH-upregulation of miR-130b-5p and circ_CUX1 that putatively target p300 and miR-130b-5p, respectively. An antisense-mediated knockdown of circ_CUX1 was performed to determine the sponging activity of circ_CUX1. Knockdown of circ_CUX1 promoted miR-130b-5p activity and reduced p300 expression, resulting in decreased Runx2 acetylation in rat osteoblastic cells. Further, bioinformatics analysis identified the possible signaling pathways that regulate Runx2 activity and osteoblast differentiation via circ_CUX1/miR-130b-5p/p300 axis. The predicted circ_CUX1/miR-130b-5p/p300 axis might pave the way for better diagnostic and therapeutic approaches for bone-related diseases. [ABSTRACT FROM AUTHOR]

Non‐coding RNAs (ncRNAs), such as miRNAs and long non‐coding RNAs (lncRNAs) have been reported as regulators of cardiovascular pathophysiology. Their transient effect and diversified mechanisms of action offer a plethora of therapeutic opportunities for cardiovascular diseases (CVDs). However, physicochemical RNA features such as charge, stability, and structural organization hinder efficient on-target cellular delivery. Here, we highlight recent preclinical advances in ncRNA delivery for the cardiovascular system using non‐viral approaches. We identify the unmet needs and advance possible solutions towards clinical translation. Finding the optimal delivery vehicle and administration route is vital to improve therapeutic efficacy and safety; however, given the different types of ncRNAs, this may ultimately not be frameable within a one-size-fits-all approach. Only one non-coding RNA (ncRNA)-based drug in clinical trials for the treatment of cardiovascular diseases is expected to act at the heart while few act at the liver, being the extrahepatic delivery of these drugs a major issue. The most explored non-viral strategies for ncRNA delivery to the heart are based in nanoparticles, extracellular vesicles, microbubbles and hydrogels. ncRNA-based drugs loaded in carriers have higher stability in serum and heart accumulation than unmodified ncRNA molecules. Targeting moieties and/or remote activation improve the delivery to the cardiovascular system. [ABSTRACT FROM AUTHOR]

• Cancer therapy has been compromised by the development of drug resistance. • The upregulation of P-glycoprotein (P-gp) can induce chemoresistance. • The overexpression of oncogenic factors mediates P-gp. • Non-coding RNAs can regulate P-gp in cancers. • Nanoparticles can affect P-gp and bypass P-gp for overcoming drug resistance. Drug resistance has compromised the efficacy of chemotherapy. The dysregulation of drug transporters including P-glycoprotein (P-gp) can mediate drug resistance through drug efflux. In this review, we highlight the role of P-gp in cancer drug resistance and the related molecular pathways, including phosphoinositide 3-kinase (PI3K)–Akt, phosphatase and tensin homolog (PTEN) and nuclear factor-κB (NF-κB), along with non-coding RNAs (ncRNAs). Extracellular vesicles secreted by the cells can transport ncRNAs and other proteins to change P-gp activity in cancer drug resistance. P-gp requires ATP to function, and the induction of mitochondrial dysfunction or inhibition of glutamine metabolism can impair P-gp function, thus increasing chemosensitivity. Phytochemicals, small molecules and nanoparticles have been introduced as P-gp inhibitors to increase drug sensitivity in human cancers. [ABSTRACT FROM AUTHOR]

• m6A methylation modifications in RNA processing, influence the function of ncRNAs and ultimately the biological processes of cancer. • M6A methylation interacting with ncRNA is strongly associated with TME formation. • Mutual regulation between m6A methylation and ncRNAs in TME creates complex networks and mediates the progression of various cancers. • ncRNAs associated with m6A methylation are expected to be new targets for cancer therapy. Cancer development is thought to be closely related to aberrant epigenetic regulation, aberrant expression of specific non-coding RNAs (ncRNAs), and tumor microenvironment (TME). The m6A methylation is one of the most abundant RNA modifications found in eukaryotes, and it can determine the fate of RNA at the post-transcriptional level through a variety of mechanisms, which affects important biological processes in the organism. The m6A methylation modification is involved in RNA processing, regulation of RNA nuclear export or localisation, RNA degradation and RNA translation. This process affects the function of mRNAs and ncRNAs, thereby influencing the biological processes of cancer cells. TME accelerates and promotes cancer generation and progression during tumor development. The m6A methylation interacting with ncRNAs is closely linked to TME formation. Mutual regulation and interactions between m6A methylation and ncRNAs in TME create complex networks and mediate the progression of various cancers. In this review, we will focus on the interactions between m6A modifications and ncRNAs in TME, summarising the molecular mechanisms by which m6A interacts with ncRNAs to affect TME and their roles in the development of different cancers. This work will help to deepen our understanding of tumourigenesis and further explore new targets for cancer therapy. [ABSTRACT FROM AUTHOR]

Bone is a connective tissue that is metabolically active and serves multiple functions, including movement, structural support, and organ protection. It is comprised primarily of three types of bone cells, namely osteoblasts, osteocytes, and osteoclasts. Osteoblasts are bone-forming cells, and the differentiation of mesenchymal stem cells towards osteoblasts is regulated by several growth factors, cytokines, and hormones via various signaling pathways, including TGF-β/BMP (transforming growth factor-beta/bone morphogenetic protein) signaling as a primary one. Non-coding RNAs (ncRNAs), such as microRNAs and long ncRNAs, play crucial roles in regulating osteoblast differentiation via the TGF-β/BMP signaling cascade. Dysregulation of these ncRNAs leads to bone-pathological conditions such as osteoporosis, skeletal dysplasia, and osteosclerosis. This review provides a concise overview of the latest advancements in understanding the involvement of ncRNAs/TGF-β/BMP axis in osteoblast differentiation. These findings have the potential to identify new molecular targets for early detection of bone metabolism disorders and the development of innovative therapy strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Peritoneal metastasis (PM) pathophysiology is complex and not fully understood. PM, originating from gastrointestinal (GI) cancer, is a condition that significantly worsens patient prognosis due to its complex nature and limited treatment options. The non-coding RNAs (ncRNAs) have been shown to play pivotal roles in cancer biology, influencing tumorigenesis, progression, metastasis, and therapeutic resistance. Increasing evidence has demonstrated the regulatory functions of different classes of ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in PM. Identifying biomarkers for early detection of PM is a crucial step towards improving patient outcomes, and how ncRNA profiles correlate with survival rates, response to therapy, and recurrence risks have raised much attention in recent years. Additionally, exploring innovative therapeutic approaches utilizing ncRNAs, such as targeted therapy and gene silencing, may offer new horizons in treating this dire condition. Recent advances in systemic treatments and the development of novel loco-regional therapies have opened doors to multimodal treatment approaches. Radical surgeries combined with hyperthermic intraperitoneal chemotherapy (HIPEC) have shown promising results, leading to extended patient survival. Current research is focused on the molecular characterization of PM, which is crucial for early detection and developing future therapeutic strategies. By summarizing the latest findings, this study underscores the transformative potential of ncRNAs in enhancing the diagnosis, prognosis, and treatment of PM in GI cancer, paving the way for more personalized and effective clinical strategies. [ABSTRACT FROM AUTHOR]

Depression, a chronic mental disorder characterized by persistent sadness, loss of interest, and difficulty in daily tasks, impacts millions globally with varying treatment options. Antidepressants, despite their long half-life and minimal effectiveness, leave half of patients undertreated, highlighting the need for new therapies to enhance well-being. Epigenetics, which studies genetic changes in gene expression or cellular phenotype without altering the underlying Deoxyribonucleic Acid (DNA) sequence, is explored in this article. This article delves into the intricate relationship between epigenetic mechanisms and depression, shedding light on how environmental stressors, early-life adversity, and genetic predispositions shape gene expression patterns associated with depression. We have also discussed Histone Deacetylase (HDAC) inhibitors, which enhance cognitive function and mood regulation in depression. Non-coding RNAs, (ncRNAs) such as Long Non-Coding RNAs (lncRNAs) and micro RNA (miRNAs), are highlighted as potential biomarkers for detecting and monitoring major depressive disorder (MDD). This article also emphasizes the reversible nature of epigenetic modifications and their influence on neuronal growth processes, underscoring the dynamic interplay between genetics, environment, and epigenetics in depression development. It explores the therapeutic potential of targeting epigenetic pathways in treating clinical depression. Additionally, it examines clinical findings related to epigenetic clocks and their role in studying depression and biological aging. [Display omitted] • This article focuses on epigenetic mechanisms and their correlation to depression. • This article explores epigenetic clocks and their correlation to health outcomes. • The article sheds light on targeting epigenetic pathways in treating depression. • The article delves into Non-coding RNAs as a promising biomarker for Major Depressive Disorder. • The article enlightens the role of Histone Deacetylase (HDAC) inhibitors in depression. [ABSTRACT FROM AUTHOR]

Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases. [ABSTRACT FROM AUTHOR]

Exposure to different environmental factors, social and socioeconomic factors promotes development of the early-life adversity (ELA) phenotype. The persistence of this phenotype across generations is an interesting phenomenon that remains unexplored. Of late many studies have focused on disease-associated outcomes of ELA following exposure during childhood but the persistence of epigenetic imprints transmitted by ELA exposed parents to their offspring remains poorly described. It is possible that both parents are able to transmit ELA-associated genetic imprints to their offspring via transgenerational inheritance mechanisms. Here, we highlight the role of the mother and father in the biological process of conception, from epigenetic reprogramming cycles to later environmental exposures. We explain some of the known determinants of ELA (pollution, socioeconomic challenges, infections, etc.) and their disease-associated outcomes. Finally, we highlight the role of epigenetics, mitochondria and ncRNAs as mechanisms mediating transgenerational inheritance. Whether these transgenerational inheritance mechanisms occur in the human context remains unclear but there is a large body of suggestive evidence in non-human models that points out to its existence. [Display omitted] • ELA phenotype transmission across generations is an underexplored phenomenon, involving parental epigenetic imprints. • Transgenerational inheritance mechanisms remain unclear in man, but substantial evidence exists in non-human models. • Epigenetics, maternal mitochondrial imprinting and non-coding RNAs mechanisms may mediate transgenerational inheritance. [ABSTRACT FROM AUTHOR]

Epidemiological evidence suggests the potential for air pollutants to induce male reproductive toxicity. In experimental studies, exposure to ozone during sensitive windows in the sperm lifecycle has been associated with impaired sperm motility. Subsequently, we sought to investigate the effects of episodic exposure to ozone during sperm maturation in the rat. Long-Evans rats were exposed to either filtered air or ozone (0.4 or 0.8 ppm) for five non-consecutive days over two weeks. Ozone exposure did not impact male reproductive organ weights or sperm motility ∼24 hours following the final exposure. Furthermore, circulating sex hormones remained unchanged despite increased T 3 and T 4 in the 0.8 ppm group. While there was indication of altered adrenergic signaling attributable to ozone exposure in the testis, there were minimal impacts on small non-coding RNAs detected in cauda sperm. Only two piwi-interacting RNAs (piRNAs) were altered in the mature sperm of ozone-exposed rats (piR-rno-346434 and piR-rno-227431). Data across all rats were next analyzed to identify any non-coding RNAs that may be correlated with reduced sperm motility. A total of 7 microRNAs (miRNAs), 8 RNA fragments, and 1682 piRNAs correlated well with sperm motility. Utilizing our exposure paradigm herein, we were unable to substantiate the relationship between ozone exposure during maturation with sperm motility. However, these approaches served to identify a suite of non-coding RNAs that were associated with sperm motility in rats. With additional investigation, these RNAs may prove to have functional roles in the acquisition of motility or be unique biomarkers for male reproductive toxicity. • Ozone exposure during sperm maturation does not affect sperm motility in rats. • Ozone exposure has minimal effects on mature sperm non-coding RNA populations but alters piR-rno-346434 and piR-rno-227431. • Increased piRNA expression was associated with reduced sperm quality in rats. [ABSTRACT FROM AUTHOR]

Telegony refers to the appearance of some characteristics of the female's previously mated male in her subsequent offspring by another male. According to evidence, telegony may occur either through the infiltration of sperm into the somatic tissues of the female genital tract or the presence of fetal genes in the mother's blood. It is highlighted that sperm penetrates into the mucosa of the uterine and possibly alters the genetic structure, affecting the embryo and enduring from one pregnancy to the next, which may be one of the potential mechanisms of telegony. Uterine fluid, uterine gland-derived histotroph, supplies key nutrients for successful embryo implantation and it is important during the first trimester, especially, because of its susceptibility to maternal states. The presence of EVs in uterine fluid (uterosomes) was reported in mice, sheep, and humans, including a wide range of biomolecules, such as proteins, and non-coding RNAs. In this review article, we presented a new idea to explain telegony. Based on our idea, after the previous male sperm entry into the female reproductive system, those sperm which do not participate in fertilization penetrate into the somatic cells of the uterus and store their genetic/epigenetic information there. The sperm of the next partner reaches a location in the female reproductive canal where it exchanges information with the uterosomes and obtains the proteins and non-coding RNAs required for fertilization, development, and implantation. [ABSTRACT FROM AUTHOR]

Identification of associations between non-coding RNAs and diseases plays an important role in the study of pathogenesis, which has been a hot topic in recent research. However, traditional methods are time-consuming to detect the associations between non-coding RNAs and diseases. Recently, associations of non-coding RNAs and diseases can be regarded as bipartite network. In this paper, we propose a novel deep multiple kernel learning method, called the multi-layer multi-kernel deep neural network (MLMKDNN). First, many feature matrices are built by multiple features of non-coding RNAs and diseases. Then, these feature matrices are mapped into kernel space and fused by deep neural network. Finally, combine two fused output of MLMKDNN as the predicted values. Three types of non-coding RNAs (miRNA, circRNA and lncRNA) are used to test the performance of MLMKDNN. Compared with other existing methods, our proposed model has high Area Under Precision Recall (AUPR) value on three types of datasets. Experimental results confirm that our method is an effective predictive tool. It provides a framework that can also be applied to the link prediction of other bipartite networks. [ABSTRACT FROM AUTHOR]

• CircRNAs are promising diagnostic and prognostic biomarkers for glioblastoma. • CircRNAs modulate various signaling pathways by regulating gene expression. • Targeting oncogenic circRNAs or restoring tumor suppressor circRNAs may provide new therapeutic avenues for glioblastoma. Glioblastoma multiforme (GBM) is the most malignant and common form of brain cancer in adults. The molecular mechanisms underlying GBM progression and resistance are complex and poorly understood. Circular RNAs (circRNAs) are a new class of non-coding RNAs formed by covalently closed loop structures with no free ends. Their circular structure makes them more stable than linear RNA and resistant to exonuclease degradation. In recent years, they have received significant attention due to their diverse functions in gene regulation and their association with various diseases, including cancer. Therefore, understanding the functions and applications of circRNAs is critical to developing targeted therapeutic interventions and advancing the field of glioblastoma cancer research. In this review, we summarized the main functions of circRNAs and their potential applications in the diagnosis, prognosis and targeted therapy of GBM. [ABSTRACT FROM AUTHOR]

Over the past decade, regulatory non-coding RNAs (ncRNAs) produced by RNA Pol II have been revealed as meaningful players in various essential cellular functions. In particular, thousands of ncRNAs are produced at transcriptional regulatory elements such as enhancers and promoters, where they may exert multiple functions to regulate proper development, cellular programming, transcription or genomic stability. Here, we review the mechanisms involving these regulatory element-associated ncRNAs, and particularly enhancer RNAs (eRNAs) and PROMoter uPstream Transcripts (PROMPTs). We contextualize the mechanisms described to the processing and degradation of these short lived RNAs. We summarize recent findings explaining how ncRNAs operate locally at promoters and enhancers, or further away, either shortly after their production by RNA Pol II, or through post-transcriptional stabilization. Such discoveries lead to a converging model accounting for how ncRNAs influence cellular fate, by acting on transcription and chromatin structure, which may further involve factors participating to 3D nuclear organization. • eRNAs & PROMPTs are dynamically produced by RNAPII at transcriptional regulatory elements. • Polyadenylation and PAXT/NEXT targeting to exosome regulate eRNAs and PROMPTs levels. • ncRNAs regulate TF recruitment and RNAPII transcription burst and pause-release. • Deregulations of eRNAs & PROMPTs can form R-loops and are associated with cancers. • ncRNAs may regulate histones PTMs, 3D genome organization and condensates. [ABSTRACT FROM AUTHOR]

• Non-coding RNAs are crucial in regulating gene expression in cardiovascular diseases. • miRNAs, lncRNAs, and circRNAs offer early detection and therapeutic intervention potential. • NcRNAs aid cardiac regeneration and influence cardiomyocyte proliferation. • Current therapies for CVDs may benefit from ncRNA-based diagnostic tools and treatments. • Exploring ncRNA expression profiles can improve the clinical management of heart conditions. Recent studies of noncoding genomes have shown important implications for regulating gene expression and genetic programs during development and their association with health, including cardiovascular disease. There are nearly 2,500 microRNAs (miRNAs), 12,000 long-chain non-coding RNAs (lncRNA), and nearly 4,000 circular RNAs (circles). Even though they do not code for proteins, they make up nearly 99% of the human genome. Non-coding RNA families (ncRNAs) have recently been discovered and established as novel and necessary controllers of cardiovascular risk factors and cellular processes and, therefore, have the potential to improve the diagnosis and prediction of cardiovascular disease. The increase in the prevalence of cardiovascular disease can be explained by the shortcomings of existing therapies, which focus only on the non-coding RNAs that protein codes for. On the other hand, recent studies point to the possibility of using ncRNAs in the early detection and intervention of CVD. These findings suggest that developing diagnostic tools and therapies based on miRNAs, lncRNAs, and circRNAs will potentially enhance the clinical management of patients with cardiovascular disease. Cardiovascular diseases include CH, HF, RHD, ACS, MI, AS, MF, ARR, and PAH, of which CH is the most common cardiovascular disease, followed by HF and RHD. This paper aims to elucidate the biological and clinical significance of miRNAs, increase, and circles, as well as their expression profiles and the possibility of regulating non-coding transcripts in cardiovascular diseases to improve the application of ncRNAs in diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic degenerative joint disease with multiple causative factors such as aging, mechanical injury, and obesity. Autophagy is a complex dynamic process that is involved in the degradation and modification of intracellular proteins and organelles under different pathophysiological conditions. Autophagy, as a cell survival mechanism under various stress conditions, plays a key role in regulating chondrocyte life cycle metabolism and cellular homeostasis. Non-coding RNAs (ncRNAs) are heterogeneous transcripts that do not possess protein-coding functions, but they can act as effective post-transcriptional and epigenetic regulators of gene and protein expression, thus participating in numerous fundamental biological processes. Increasing evidence suggests that ncRNAs, autophagy, and their crosstalk play crucial roles in OA pathogenesis. Therefore, we summarized the complex role of autophagy in OA chondrocytes and focused on the regulatory role of ncRNAs in OA-associated autophagy to elucidate the complex pathological mechanisms of the ncRNA-autophagy network in the development of OA, thus providing new research targets for the clinical diagnosis and treatment of OA. • Autophagy is a double-edged sword in regulating the survival or death of OA chondrocytes. • NcRNAs act as key regulators of chondrocytes autophagy to modulate OA development. • Novel strategies and challenges in targeting the ncRNAs-autophagy axis for OA treatment are discussed. [ABSTRACT FROM AUTHOR]

Phosphatase and tensin homolog (PTEN), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) signaling pathways contribute to the development of several cancers, including multiple myeloma (MM). PTEN is a tumor suppressor that influences the PI3K/Akt/mTOR pathway, which in turn impacts vital cellular processes like growth, survival, and treatment resistance. The current study aims to present the role of PTEN and PI3K/Akt/mTOR signaling in the development of MM and its response to treatment. In addition, the molecular interactions in MM that underpin the PI3K/Akt/mTOR pathway and address potential implications for the development of successful treatment plans are also discussed in detail. We investigate their relationship to both upstream and downstream regulators, highlighting new developments in combined therapies that target the PTEN/PI3K/Akt axis to overcome drug resistance, including the use of PI3K and mitogen-activated protein kinase (MAPK) inhibitors. We also emphasize that PTEN/PI3K/Akt pathway elements may be used in MM diagnosis, prognosis, and therapeutic targets. [Display omitted] [ABSTRACT FROM AUTHOR]

Breast and lung cancers are leading causes of death among patients, with their global mortality and morbidity rates increasing. Conventional treatments often prove inadequate due to resistance development. The alteration of molecular interactions may accelerate cancer progression and treatment resistance. SOX2, known for its abnormal expression in various human cancers, can either accelerate or impede cancer progression. This review focuses on examining the role of SOX2 in breast and lung cancer development. An imbalance in SOX2 expression can promote the growth and dissemination of these cancers. SOX2 can also block programmed cell death, affecting autophagy and other cell death mechanisms. It plays a significant role in cancer metastasis, mainly by regulating the epithelial-to-mesenchymal transition (EMT). Additionally, an imbalanced SOX2 expression can cause resistance to chemotherapy and radiation therapy in these cancers. Genetic and epigenetic factors may affect SOX2 levels. Pharmacologically targeting SOX2 could improve the effectiveness of breast and lung cancer treatments. [ABSTRACT FROM AUTHOR]

One of the major diseases affecting people globally is colorectal cancer (CRC), which is primarily caused by a lack of effective medical treatment and a limited understanding of its underlying mechanisms. Cellular autophagy functions to break down and eliminate superfluous proteins and substances, thereby facilitating the continual replacement of cellular elements and generating vital energy for cell processes. Non-coding RNAs and exosomal ncRNAs have a crucial impact on regulating gene expression and essential cellular functions such as autophagy, metastasis, and treatment resistance. The latest research has indicated that specific ncRNAs and exosomal ncRNA to influence the process of autophagy in CRC cells, which could have significant consequences for the advancement and treatment of this disease. It has been determined that a variety of ncRNAs have a vital function in regulating the genes essential for the formation and maturation of autophagosomes. Furthermore, it has been confirmed that ncRNAs have a considerable influence on the signaling pathways associated with autophagy, such as those involving AMPK, AKT, and mTOR. Additionally, numerous ncRNAs have the potential to affect specific genes involved in autophagy. This study delves into the control mechanisms of ncRNAs and exosomal ncRNAs and examines how they simultaneously influence autophagy in CRC. [ABSTRACT FROM AUTHOR]

Atopic dermatitis, commonly referred to as atopic eczema, is a persistent inflammatory skin disorder that predominantly manifests in children but may endure into adulthood. Its clinical management poses challenges due to the absence of a definitive cure, and its prevalence varies across ethnicities, genders, and geographic locations. The epigenetic landscape of AD includes changes in DNA methylation, changes in histone acetylation and methylation, and regulation by non-coding RNAs. These changes affect inflammatory and immune mechanisms, and research has identified AD-specific variations in DNA methylation, particularly in the affected epidermis. Histone modifications, including acetylation, have been associated with the disruption of skin barrier function in AD, suggesting the potential therapeutic benefit of histone deacetylase inhibitors such as belinostat. Furthermore, non-coding RNAs, particularly microRNAs and long non-coding RNAs (lncRNAs), have been implicated in modulating various cellular processes central to AD pathogenesis. Therapeutic implications in AD include the potential use of DNA methylation inhibitors and histone deacetylase inhibitors to correct aberrant methylation patterns and modulate gene expression related to immune responses and skin barrier functions. Additionally, the emerging role of lncRNAs suggests the possibility of using small interfering RNAs or antisense oligonucleotides to inhibit lncRNAs and adjust their regulatory impact on gene expression. In conclusion, the importance of epigenetic elements in AD is becoming increasingly clear as studies highlight the contribution of DNA methylation, histone modifications and, control by non-coding RNAs to the onset and progression of the disease. Understanding these epigenetic changes provides valuable insights for developing targeted therapeutic strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Systemic autoimmune diseases are complex conditions characterized by an immune system dysregulation and an aberrant activation against self-antigens, leading to tissue and organ damage. Even though genetic predisposition plays a role, it cannot fully explain the onset of these diseases, highlighting the significant impact of non-heritable influences such as environment, hormones and infections. The exposome represents all those factors, ranging from chemical pollutants and dietary components to psychological stressors and infectious agents. Epigenetics, which studies changes in gene expression without altering the DNA sequence, is a crucial link between exposome and the development of autoimmune diseases. Key epigenetic mechanisms include DNA methylation, histone modifications, and non-coding RNAs. These epigenetic modifications could provide a potential piece of the puzzle in understanding systemic autoimmune diseases and their connection with the exposome. In this work we have collected the most important and recent evidence in epigenetic changes linked to systemic autoimmune diseases (systemic lupus erythematosus, idiopathic inflammatory myopathies, ANCA-associated vasculitis, and rheumatoid arthritis), emphasizing the roles these changes may play in disease pathogenesis, their potential as diagnostic biomarkers and their prospective in the development of targeted therapies. [ABSTRACT FROM AUTHOR]

Autophagy, a self-digestion mechanism, has emerged as a promising target in the realm of cancer therapy, particularly in bladder cancer (BCa), a urological malignancy characterized by dysregulated biological processes contributing to its progression. This highly conserved catabolic mechanism exhibits aberrant activation in pathological events, prominently featured in human cancers. The nuanced role of autophagy in cancer has been unveiled as a double-edged sword, capable of functioning as both a pro-survival and pro-death mechanism in a context-dependent manner. In BCa, dysregulation of autophagy intertwines with cell death mechanisms, wherein pro-survival autophagy impedes apoptosis and ferroptosis, while pro-death autophagy diminishes tumor cell survival. The impact of autophagy on BCa progression is multifaceted, influencing metastasis rates and engaging with the epithelial-mesenchymal transition (EMT) mechanism. Pharmacological modulation of autophagy emerges as a viable strategy to impede BCa progression and augment cell death. Notably, the introduction of nanoparticles for targeted autophagy regulation holds promise as an innovative approach in BCa suppression. This review underscores the intricate interplay of autophagy with cell death pathways and its therapeutic implications in the nuanced landscape of bladder cancer. [Display omitted] • Bladder cancer (BCa) is a threat to the urological system. • Autophagy is an evolutionary conserved catabolic mechanism providing cellular homeostasis. • Aberrant activation of autophagy can change growth and metastasis of BCa. • Dysregulation of autophagy causes drug resistance and radioresistance in BCa. • Drugs and nanomaterials regulating autophagy can treat BCa. [ABSTRACT FROM AUTHOR]

[Display omitted] Non-coding RNAs (ncRNAs) are an assorted collection of transcripts that are not translated into proteins. Since their discovery, ncRNAs have gained prominence as crucial regulators of various biological functions across diverse cell types and tissues, and their abnormal functioning has been implicated in disease. Notably, extensive research has focused on the relationship between microRNAs (miRNAs) and human cancers, although other types of ncRNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are also emerging as significant contributors to human disease. In this review, we provide a comprehensive summary of our current knowledge regarding the roles of miRNAs, lncRNAs, and circRNAs in cancer and other major human diseases, particularly cancer, cardiovascular, neurological, and infectious diseases. Moreover, we discuss the potential utilization of ncRNAs as disease biomarkers and as targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Oral potentially malignant disorders (OPMD) are lesions that may precede the onset of cancers in the oral cavity, and oral submucosal fibrosis (OSF) is one of the OPMD that is usually found in the buccal mucosa. Considerable effort has been made to elucidate the pathogenesis of OSF, and emerging evidence has suggested that microRNAs may play significant roles in the development of OSF. Several studies demonstrated that aberrant expression of miRNAs is also observed in the fibrotic BMFs (fBMFs) derived from OSF tissues. For instance, it has been shown that miR-10b, miR-21, and miR-1246 are significantly elevated, and miR-29b, miR-200b, and miR-200c are reduced in fBMFs. This review systematically summarizes the current knowledge regarding the aberrant expression of microRNAs, molecular mechanisms underlying oral fibrogenesis by the dysregulated microRNAs, and how the interaction between microRNAs and long non-coding RNAs contributes to the progression of OSF. An overview of the modes of action by these microRNAs will provide a fundamental basis for clinical application. [ABSTRACT FROM AUTHOR]

• Childhood trauma (CT) is a major risk factor for neuropsychiatric disorders • Long-term epigenetic changes occur in the brain of adults with a history of CT • Affected pathways include the HPA axis, BDNF, oxytocin and neurotransmitter signaling • Pharmacological and psychological interventions may counteract CT-induced changes. Childhood trauma (CT) can have persistent effects on the brain and is one of the major risk factors for neuropsychiatric diseases in adulthood. Recent advances in the field of epigenetics suggest that epigenetic factors such as DNA methylation and histone modifications, as well as regulatory processes involving non-coding RNA are associated with the long-term sequelae of CT. This narrative review summarizes current knowledge on the epigenetic basis of CT and describes studies in animal models and human subjects examining how the epigenome and transcriptome are modified by CT in the brain. It discusses psychological and pharmacological interventions that can counteract epigenetic changes induced by CT and the need to establish longitudinal assessment after CT for developing more effective diagnostics and treatment strategies based on epigenetic targets. [ABSTRACT FROM AUTHOR]

Natural products (NPs), especially those from traditional herbal medicines, can evidently modulate human gene expression at multiple levels, leading to a wide diversity of bioactivities. Although numerous bio-functions of NPs for human body have been found, there is little understanding about how NPs achieve it, as less attention was drawn to the definite mechnism by which NPs regulate gene expression. Furthermore, based on the rapidly advancing knowledge of mechanisms for gene regulation in recent years, newly-understood mechanisms, such as post-transcriptional regulation, are found to be involved in NP-elicited bio-effects, providing a new perspective on understanding the role of NPs in gene expression. Therefore, in the current review, we summarize the function of NPs in gene expression from the perspectives of transcriptional, post-transcriptional, and post-translational regulation, which will reinforce the understanding of NP-induced effects in gene expression and facilitate the exploration of more NPs with potential therapeutic effects. [ABSTRACT FROM AUTHOR]

Adverse cardiac remodeling and tissue damage following heart disease is strongly associated with chronic low grade inflammation. The mechanisms underlying persisting inflammatory signals are not fully understood, but may involve defective and/or non-responsive transcriptional and post-transcriptional regulatory mechanisms. In the current study, we aimed to identify novel mediators and pathways involved in processes associated with inflammation in the development and maintenance of cardiac disease. We performed RNA sequencing analysis of cardiac tissue from patients undergoing coronary artery bypass grafting (CABG) or aortic valve replacement (AVR) and compared with control tissue from multi-organ donors. Our results confirmed previous findings of a marked upregulated inflammatory state, but more importantly, we found pronounced reduction of non-protein coding genes, particularly long non-coding RNAs (lncRNA), including several lncRNAs known to be associated with inflammation and/or cardiovascular disease. In addition, Gene Set Enrichment Analysis revealed markedly downregulated microRNA pathways, resulting in aberrant expression of other genes, particularly γ-protocadherins. Our data suggest that aberrant expression of non-coding gene regulators comprise crucial keys in the progression of heart disease, and may be pivotal for chronic low grade inflammation associated with cardiac dysfunction. By unmasking atypical γ-protocadherin expression as a prospective genetic biomarker of myocardial dysfunction, our study provides new insight into the complex molecular framework of heart disease. Creating new approaches to modify non-coding gene regulators, such as those identified in the current study, may define novel strategies to shift γ-protocadherin expression, thereby normalizing part of the molecular architecture associated with heart disease. • Lnc-RNAs may exert crucial links between cardiac inflammation and heart disease. • MiR133A/B-, miR448- and miR518C- signaling is strongly attenuated in heart disease. • γ-protocadherins might be novel genetic biomarkers of myocardial dysfunction. [ABSTRACT FROM AUTHOR]

• Exercise induces a profound alteration in epigenetics, which mediates the beneficial effects of exercise. • Exercise not only modifies epigenetics in the heart to promote cardiac health, but also modifies epigenetics in other tissues, which reduces risks of cardiac disease or affords cardioprotection through exerkines. • Exercise-modulated circulating non-coding RNAs are secreted from multiple tissues and shuttled by exosomes, acting as a new kind of exerkine that plays an important role in cardioprotection. With the rising incidence of cardiovascular diseases, the concomitant mortality and morbidity impose huge burdens on quality of life and societal costs. It is generally accepted that physical inactivity is one of the major risk factors for cardiac disease and that exercise benefits the heart in both physiological and pathologic conditions. However, the molecular mechanisms governing the cardioprotective effects exerted by exercise remain incompletely understood. Most recently, an increasing number of studies indicate the involvement of epigenetic modifications in the promotion of cardiac health and prevention of cardiac disease. Exercise and other lifestyle factors extensively induce epigenetic modifications, including DNA/RNA methylation, histone post-translational modifications, and non-coding RNAs in multiple tissues, which may contribute to their positive effects in human health and diseases. In addition, several studies have shown that maternal or paternal exercise prevents age-associated or high-fat diet-induced metabolic dysfunction in the offspring, reinforcing the importance of epigenetics in mediating the beneficial effects of exercise. It has been shown that exercise can directly modify cardiac epigenetics to promote cardiac health and protect the heart against various pathological processes, or it can modify epigenetics in other tissues, which reduces the risk of cardiac disease and affords cardioprotection through exerkines. An in-depth understanding of the epigenetic landscape of cardioprotective response to exercise will provide new therapeutic targets for cardiac diseases. This review, therefore, aimed to acquaint the cardiac community with the rapidly advancing and evolving field of exercise and epigenetics. [Display omitted] [ABSTRACT FROM AUTHOR]

• Brain development is a dynamic, prolonged, and complex process. • Disruption of developmental events by internal genetic factors or external environmental stress can cause brain developmental disorders. • Emerging evidence suggests ncRNAs are pivotal molecules that are involved in brain development in health and disease. • ncRNA signaling can offer possible pharmacological targets for neuroprotection and biomarkers for brain developmental disorders. Brain development is a dynamic and lengthy process that includes cell proliferation, migration, neurogenesis, gliogenesis, synaptogenesis, and pruning. Disruption of any of these developmental events can result in long-term outcomes ranging from brain structural changes, to cognitive and behavioral abnormality, with the mechanisms largely unknown. Emerging evidence suggests non-coding RNAs (ncRNAs) as pivotal molecules that participate in normal brain development and neurodevelopmental disorders. NcRNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are transcribed from the genome but not translated into proteins. Many ncRNAs have been implicated as tuners of cell fate. In this review, we started with an introduction of the current knowledge of lncRNAs and miRNAs, and their potential roles in brain development in health and disorders. We then reviewed and discussed the evidence of ncRNA involvement in abnormal brain development resulted from alcohol, anesthetic drugs, nicotine, and viral infections. The complex connections among these ncRNAs were also discussed, along with potential overlapping ncRNA mechanisms, possible pharmacological targets for therapeutic/neuroprotective interventions, and potential biomarkers for brain developmental disorders. [ABSTRACT FROM AUTHOR]

The mechanisms occurring during sepsis that produce an increased risk of cardiovascular (CV) disease (CVD) are poorly understood. Even less information exists regarding CV dysfunction as a complication of sepsis, particularly for sepsis-induced cardiomyopathy. However, recent research has demonstrated that non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, play a crucial role in genetic reprogramming, gene regulation, and inflammation during the development of CVD. Here we describe experimental findings showing the importance of non-coding RNAs mediating relevant mechanisms underlying CV dysfunction after sepsis, so contributing to sepsis-induced cardiomyopathy. Importantly, non-coding RNAs are critical novel regulators of CVD risk factors. Thus, they are potential candidates to improve diagnostics and prognosis of sepsis-induced cardiomyopathy and other CVD events occurring after sepsis and set the basis to design novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Plant-nematode associations are the most imperative area of study that forms the basis to understand their regulatory networks and coordinated functional aspects. Nematodes are highly parasitic organisms known so far, to cause relentless damage towards agricultural crops on a global scale. They pierce the roots of host plants and form neo-plastic feeding structures to extract out resources for their functional development. Moreover, they undergo re-differentiation within plant cells to form giant multi-nucleate feeding structures or syncytium. All these processes are facilitated by numerous transcriptomic, proteomic, metabolomic and epigenetic modifications, that regulate different biological attractions among plants and nematodes. Nevertheless, these mechanisms are quite remarkable and have been explored in the present review. Here, we have shed light on genomic as well as genetic approaches to acquire an effective understanding regarding plant-nematode associations. Transcriptomics have revealed an extensive network to unravel feeding mechanism of nematodes through gene-expression programming of target genes. Also, the regulatory circuits of epigenetic alterations through DNA-methylation, non-coding RNAs and histone modifications very well explain epigenetic profiling within plants. Since decades, research have observed many intricacies to elucidate the dynamic nature of epigenetic modulations in plant-nematode attractions. By this review, we have highlighted the functional aspects of small RNAs in inducing plant-nematode parasitism along with the putative role of miRNAs. These RNAs act as chief genetic elements to mediate the expressional changes in plants through post-transcriptional silencing of various effector proteins as well as transcriptional factors. A pragmatic role of miRNAs in modulating gene expression in nematode infection and feeding site development have also been reviewed. Hence, they have been considered master regulators for functional reprogramming the expression during establishment of feeding sites. We have also encapsulated the advancement of genome-broadened DNA-methylation and untangled the nematode mediated dynamic alterations within plant methylome along with assessing transcriptional activities of various genes and transposons. In particular, we have highlighted the role of effector proteins in stimulating epigenetic changes. Finally, we have emerged towards a molecular-based core understanding about plant-nematode associations. • Nematodes pierce plants to form neo-plastic feeding structures or syncytium. • Epigenetic modifications are substantial for regulating plant-nematode attractions. • Regulatory circuits are DNA-methylation, non-coding RNAs and histone modifications. • Small RNAs and micro RNAs are crucial for nematode parasitism in plants. • Plant methylome undergo transcriptional changes, unravelled by genome-based approaches. [ABSTRACT FROM AUTHOR]

Ginsenosides are a series of glycosylated triterpenoids which belong to protopanaxadiol (PPD)-, protopanaxatriol (PPT)-, ocotillol (OCT)- and oleanane (OA)-type saponins known as active compounds of Panax genus. They are accumulated in plant roots, stems, leaves, and flowers. The content and composition of ginsenosides are varied in different ginseng species, and in different parts of a certain plant. In this review, we summarized the representative saponins structures, their distributions and the contents in nearly 20 Panax species, and updated the biosynthetic pathways of ginsenosides focusing on enzymes responsible for structural diversified ginsenoside biosynthesis. We also emphasized the transcription factors in ginsenoside biosynthesis and non-coding RNAs in the growth of Panax genus plants, and highlighted the current three major biotechnological applications for ginsenosides production. This review covered advances in the past four decades, providing more clues for chemical discrimination and assessment on certain ginseng plants, new perspectives for rational evaluation and utilization of ginseng resource, and potential strategies for production of specific ginsenosides. Ginsenosides are produced mainly via MVA pathway. Functional genes are regulated by multiple elicitors through different transcriptional factors, which together play pivotal roles in ginsenoside structure diversities. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Radiotherapy stimulates an aberrant cell epigenome to encourage radiation resistance. • Epigenetic drugs reverse radioresistance and break tumor growth. • Cancer stem cells are enrich in tumor radioresistant through an epigenetic network. • Aberrant histone code mainly promote DNA repair in the adaptive radioresistance. • Cooperative feedback between lncRNAs and miRNAs circumvent the effect of radiotherapy. • miR-145 is negatively controlled by lncRNAs to promote radioresistance in many tumor types. • The role of epi-miRNAs in radioresistance is unknown. Radiotherapy, in addition to surgery and systemic chemotherapy, remains the core of the current clinical management of cancer. Radioresistance is one of the major causes of disease progression and mortality in cancer; therefore, it is a significant challenge in the treatment of locally advanced, recurrent and metastatic cancer. Epigenetic mechanisms that control hallmarks of cancer have a key role in the development of radiation resistance of cancer cells. Recent advances in DNA methylation, histone modification, chromatin remodeling and non-coding RNAs identified in the control of signal transduction pathways in cancer and cancer stem cells have provided even greater promise in the improvement of understanding cancer radioresistance. Many epigenetic drugs that target epigenetic enzymes revert the radioresistant phenotypes decreasing the possibility that resistant cancer cells will develop refractory tumors to radiotherapy. Epigenetic profiles identified as regulators of DNA damage repair, hypoxia, cell survival, apoptosis and invasion are determinants in the development of tumor radioresistance; hence, they also are promising in personalized medicine to develop novel targeted therapies or biomarkers to follow-up the effectiveness of radiotherapy. Now, it is clear that radiotherapy can influence a complex epigenetic network for transcriptional reprogramming, enabling the cells to adapt and avoid the effect of radiotherapy. This review aims to highlight the epigenetic modifications identified in cancer radioresistance and to discuss approaches to disable epigenetic networks to increase the sensitivity and specificity of radiotherapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) stands as a formidable global health challenge due to its prevalence, marked by high mortality and morbidity rates. This cancer type exhibits a multifaceted etiology, prominently linked to viral infections, non-alcoholic fatty liver disease, and genomic mutations. The inherent heterogeneity of HCC, coupled with its proclivity for developing drug resistance, presents formidable obstacles to effective therapeutic interventions. Autophagy, a fundamental catabolic process, plays a pivotal role in maintaining cellular homeostasis, responding to stressors such as nutrient deprivation. In the context of HCC, tumor cells exploit autophagy, either augmenting or impeding its activity, thereby influencing tumorigenesis. This comprehensive review underscores the dualistic role of autophagy in HCC, acting as both a pro-survival and pro-death mechanism, impacting the trajectory of tumorigenesis. The anti-carcinogenic potential of autophagy is evident in its ability to enhance apoptosis and ferroptosis in HCC cells. Pertinently, dysregulated autophagy fosters drug resistance in the carcinogenic context. Both genomic and epigenetic factors can regulate autophagy in HCC progression. Recognizing the paramount importance of autophagy in HCC progression, this review introduces pharmacological compounds capable of modulating autophagy—either inducing or inhibiting it, as promising avenues in HCC therapy. [Display omitted] • Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. • Autophagy is a "self-digestion" mechanism with upregulation or downregulation in human cancers. • Aberrant activation of autophagy changes proliferation and metastasis of HCC. • Pro-survival autophagy activation stimulates drug resistance and radioresistance. • Nanoparticles and pharmacological compounds regulate autophagy in HCC therapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a malignant liver cancer characterized by aggressive progression, unfavorable prognosis, and an increasing global health burden. Therapies that precisely target immunological checkpoints and immune cells have gained significant attention as possible therapeutics in recent years. In truth, the efficacy of immunotherapy is heavily contingent upon the tumor microenvironment (TME). Recent studies have indicated that exosomes serve as a sophisticated means of communication among biomolecules, executing an essential part in the TME of immune suppression. Exosomal non-coding RNAs (ncRNAs) can induce the activation of tumor cells and immunosuppressive immune cells that suppress the immune system, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), CD+8 T cells, regulatory T cells (Tregs), and regulatory B cells (Bregs). This cell-cell crosstalk triggered by exosomal ncRNAs promotes tumor proliferation and metastasis, angiogenesis, malignant phenotype transformation, and drug resistance. Hence, it is imperative to comprehend how exosomal ncRNAs regulate tumor cells or immune cells within the TME to devise more comprehensive and productive immunotherapy programs. This study discusses the features of exosomal ncRNAs in HCC and how the activation of the exosomes redefines the tumor's immunosuppressive microenvironment, hence facilitating the advancement of HCC. Furthermore, we also explored the potential of exosomal ncRNAs as a viable biological target or natural vehicle for HCC therapy. [Display omitted] • Exosomes are crucial in establishing the immunosuppressive TME of HCC. • A summary of the abundance and function of exosomal ncRNAs in HCC. • Exosomal ncRNAs can activate tumor and immunosuppressive immune cells. • Exosomal ncRNAs as a biological target or natural vehicle for HCC treatment. [ABSTRACT FROM AUTHOR]

Non-coding RNA (ncRNA)-based therapies entail delivering ncRNAs to cells to regulate gene expression and produce proteins that combat infections, cancer, neurological diseases, and bone abnormalities. Nevertheless, the therapeutic potential of these ncRNAs has been limited due to the difficulties in delivering them to specific cellular targets within the body. Chitosan (CS), a biocompatible cationic polymer, interacts with negatively charged RNA molecules to form stable complexes. It is a promising biomaterial to develop nanocarriers for ncRNA delivery, overcoming several disadvantages of traditional delivery systems. CS-based nanocarriers can protect ncRNAs from degradation and target-specific delivery by surface modifications and intracellular release profiles over an extended period. This review briefly summarizes the recent developments in CS nanocarriers' synthesis and design considerations and their applications in ncRNA therapeutics for treating various diseases. We also discuss the challenges and limitations of CS-based nanocarriers for ncRNA therapeutics and potential strategies for overcoming these challenges. [ABSTRACT FROM AUTHOR]

Successful male reproductive development is the guarantee for sexual reproduction of flowering plants. Male reproductive development is a complicated and multi-stage process that integrates physiological processes and adaptation and tolerance to a myriad of environmental stresses. This well-coordinated process is governed by genetic and epigenetic machineries. Non-coding RNAs (ncRNAs) play pleiotropic roles in the plant growth and development. The identification, characterization and functional analysis of ncRNAs and their target genes have opened a new avenue for comprehensively revealing the regulatory network of male reproductive development and its response to environmental stresses in plants. This review briefly addresses the types, origin, biogenesis and mechanisms of ncRNAs in plants, highlights important updates on the roles of ncRNAs in regulating male reproductive development and emphasizes the contribution of ncRNAs, especially miRNAs and lncRNAs, in responses to abiotic stresses during this unique process in flowering plants. • Male reproductive development is high susceptible to a myriad of environmental stresses. • ncRNAs are involved in the coordinated regulation of male reproductive development. • ncRNAs contributes to adaptation and tolerance to abiotic stresses during male reproductive development. [ABSTRACT FROM AUTHOR]

Sepsis causes significant morbidity and mortality worldwide, most surviving patients show acute or chronic mental disorders, which are known as sepsis-associated encephalopathy (SAE). SAE involves many pathological processes, including the blood-brain barrier (BBB) damage. The BBB is located at the interface between the central nervous system and the surrounding environment, which protects the central nervous system (CNS) from the invasion of exogenous molecules, harmful substances or microorganisms in the blood. Recently, a growing number of studies have indicated that the BBB destruction was involved in SAE and played an important role in SAE-induced brain injury. In the present review, we firstly reveal the pathological processes of SAE such as the neurotransmitter disorders, oxidative stress, immune dysfunction and BBB destruction. Moreover, we introduce the structure of BBB, and describe the immune cells including microglia and astrocytes that participate in the BBB destruction after SAE. Furthermore, in view of the current research on non-coding RNAs (ncRNAs), we explain the regulatory mechanism of ncRNAs including long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) on BBB in the processes of SAE. Finally, we propose some challenges and perspectives of regulating BBB functions in SAE. Hence, on the basis of these effects, both immune cells and ncRNAs may be developed as therapeutic targets to protect BBB for SAE patients. • SAE is an important cause of disability and death worldwide. • BBB damage is an important pathological process of SAE. • NcRNAs have regulatory roles on BBB in the processes of SAE. • Some unique features and innovations of this review are discussed. • Many challenges on the researches of BBB in SAE are discussed. [ABSTRACT FROM AUTHOR]

Brain functionality relies on finely tuned regulation of gene expression by networks of non-coding RNAs (ncRNAs) such as the one composed by the circular RNA ciRS-7 (also known as CDR1as), the microRNA miR-7, and the long ncRNA Cyrano. We describe ischemia-induced alterations in the ncRNA network both in vitro and in vivo and in transgenic mice lacking ciRS-7 or miR-7. Our data show that cortical neurons downregulate ciRS-7 and Cyrano and upregulate miR-7 expression during ischemia. Mice lacking ciRS-7 exhibit reduced lesion size and motor impairment, while the absence of miR-7 alone results in increased ischemia-induced neuronal death. Moreover, miR-7 levels in pyramidal excitatory neurons regulate neurite morphology and glutamatergic signaling, suggesting a potential molecular link to the in vivo phenotype. Our data reveal the role of ciRS-7 and miR-7 in modulating ischemic stroke outcome, shedding light on the pathophysiological function of intracellular ncRNA networks in the brain. [Display omitted] • Brain ischemia activates the ciRS-7, miR-7, and Cyrano non-coding network • miR-7 prevents ischemia-induced secondary cell death • ciRS-7 safeguards miR-7 targeting in physiological conditions • Unlocking ciRS-7 buffering regulates glutamatergic signaling via miR-7 targeting Scoyni et al. show the activation of the non-coding RNA network involving ciRS-7, miR-7, and Cyrano in response to ischemic conditions both in vitro and in vivo. This intricate system modulates the impact of miR-7 on mRNA targets, mitigating neuronal excitotoxicity through the regulation of glutamatergic signaling. [ABSTRACT FROM AUTHOR]

A category of very uncommon systemic inflammatory blood vessel illnesses known as vasculitides. The pathogenesis and etiology of vasculitis are still poorly known. Despite all of the progress made in understanding the genetics and causes behind vasculitis, there is still more to learn. Epigenetic dysregulation is a significant contributor to immune-mediated illnesses, and epigenetic aberrancies in vasculitis are becoming more widely acknowledged. Less than 2 % of the genome contains protein-encoding DNA. Studies have shown that a variety of RNAs originating from the non-coding genome exist. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) have attracted the most attention in recent years as they are becoming more and more important regulators of different biological processes, such as diseases of the veins. Extracellular vehicles (EVs) such as exosomes, are membrane-bound vesicular structures that break free either during programmed cell death, such as apoptosis, pyroptosis, and necroptosis or during cell activation. Exosomes may be involved in harmful ways in inflammation, procoagulation, autoimmune reactions, endothelial dysfunction/damage, intimal hyperplasia and angiogenesis, all of which may be significant in vasculitis. Herein, we summarized various non-coding RNAs that are involved in vasculitides pathogenesis. Moreover, we highlighted the role of exosomes in vasculitides. [ABSTRACT FROM AUTHOR]

The pivotal regulatory role of non-coding RNAs (ncRNAs), especially exosomal ncRNAs, in ferroptosis significantly influences cancer cell fate. This review explores their involvement across various human cancers, focusing on microRNAs (miRNA), long non-coding RNAs (lncRNA), and circular RNAs (circRNA). These ncRNAs either stimulate or inhibit ferroptosis by targeting key components, impacting cancer susceptibility to this form of cell death. Specific studies in lung, gastric, liver, cervical, bladder, pancreatic, and osteosarcoma cancers underscore the crucial role of exosomal ncRNAs in modulating ferroptosis, influencing cancer progression, and therapeutic responses. Emphasizing the therapeutic potential of exosomal ncRNAs, we discuss their ability to deliver circRNA, miRNA, and lncRNA to target cells. Despite being in early stages with challenges in bioengineering for drug delivery, these studies hold promise for future clinical applications. Noteworthy findings include inhibiting exosome production to overcome ferroptosis resistance in lung adenocarcinoma and the potential of exosomal DACT3-AS1 to sensitize gastric cancer cells to ferroptosis. The review concludes by highlighting exosomal ncRNAs like miR-4443 and miR-660–5p as promising therapeutic targets, offering avenues for precise cancer interventions by modulating signaling pathways and sensitizing cells to ferroptosis. Overall, this review enhances our understanding of cancer pathogenesis and presents new horizons for targeted therapeutic interventions, revealing the intricate interplay between exosomal ncRNAs and ferroptosis. [Display omitted] • Ferroptosis-related non-coding RNAs are novel regulators in cancers. • Delivering tumor suppressive exosomal non-coding RNAs hinders tumor progression. • Inhibition of oncogene exosomal non-coding RNAs overcomes ferroptosis resistance. [ABSTRACT FROM AUTHOR]

Melanoma is one of the most lethal cutaneous malignancies. Despite great advances in radiotherapy, chemotherapy, and immunotherapy, the survival rate and prognosis of patients with melanoma remain poor. The abundant and sophisticated reciprocal communication network between melanoma cells and non-tumor cells contributes to the high heterogeneity of the melanoma microenvironment and is intimately related to varying treatment responses and clinical courses. Extracellular vesicles (EVs) are membrane structures generated by nearly all cell types. EVs contain biologically active molecules, mainly comprising proteins, lipids, and RNAs, and undoubtedly play multifaceted roles in numerous diseases, represented by melanoma. Non-coding RNAs (ncRNAs) mainly encompass long non-coding RNAs, microRNAs, and circular RNAs and constitute the majority of the human transcriptome. Multiple ncRNAs encapsulated in EVs coordinate various pathophysiological processes in melanoma. This review summarizes the mechanisms by which EV-ncRNAs modulate biological behaviors and immunity, and their potential diagnostic and therapeutic applications in melanoma. Undoubtedly, further insight into EV-ncRNAs and their functions in melanoma will contribute to the clinical treatment of melanoma and the implementation of precision medicine. [Display omitted] • EV-ncRNAs mediate melanoma resistance to drugs including Vemurafenib and the pharmacology for metformin with cisplatin. • EV-ncRNAs are pivotal in reconfiguring the biological behavior of melanoma and participating in melanoma diagnosis. • Multiple EV-ncRNAs derived from melanoma microenvironment participate in melanoma growth, metastasis, and Warburg effects. • EV-ncRNAs can regulate the immune responses of melanoma by remodeling recipient immune cells. • EV-ncRNAs in serum are promising biomarkers for liquid biopsy and possible therapeutic targets for melanoma. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) continues to be a major health concern worldwide, with its resistance to chemotherapy and radiation therapy presenting major hurdles in successful treatment. While patients with localized prostate cancer generally have a good survival rate, those with metastatic prostate cancer often face a grim prognosis, even with aggressive treatments using various methods. The high mortality rate in severe cases is largely due to the lack of treatment options that can offer lasting results, especially considering the significant genetic diversity found in tumors at the genomic level. This comprehensive review examines the intricate molecular mechanisms governing resistance in PCa, emphasising the pivotal contributions of non-coding RNAs (ncRNAs). We delve into the diverse roles of microRNAs, long ncRNAs, and other non-coding elements as critical regulators of key cellular processes involved in CR & RR. The review emphasizes the diagnostic potential of ncRNAs as predictive biomarkers for treatment response, offering insights into patient stratification and personalized therapeutic approaches. Additionally, we explore the therapeutic implications of targeting ncRNAs to overcome CR & RR, highlighting innovative strategies to restore treatment sensitivity. By synthesizing current knowledge, this review not only provides a comprehension of the chemical basis of resistance in PCa but also identifies gaps in knowledge, paving the way for future research directions. Ultimately, this exploration of ncRNA perspectives offers a roadmap for advancing precision medicine in PCa, potentially transforming therapeutic paradigms and improving outcomes for patients facing the challenges of treatment resistance. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is one of the primary factors that produces treatment failure in patients receiving cancer chemotherapy. MDR is a complex multifactorial phenomenon, characterized by a decrease or abrogation of the efficacy of a wide spectrum of anticancer drugs that are structurally and mechanistically distinct. The overexpression of the ATP-binding cassette (ABC) transporters, notably ABCG2 and ABCB1, are one of the primary mediators of MDR in cancer cells, which promotes the efflux of certain chemotherapeutic drugs from cancer cells, thereby decreasing or abolishing their therapeutic efficacy. A number of studies have suggested that non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play a pivotal role in mediating the upregulation of ABC transporters in certain MDR cancer cells. This review will provide updated information about the induction of ABC transporters due to the aberrant regulation of ncRNAs in cancer cells. We will also discuss the measurement and biological profile of circulating ncRNAs in various body fluids as potential biomarkers for predicting the response of cancer patients to chemotherapy. Sequence variations, such as alternative polyadenylation of mRNA and single nucleotide polymorphism (SNPs) at miRNA target sites, which may indicate the interaction of miRNA-mediated gene regulation with genetic variations to modulate the MDR phenotype, will be reviewed. Finally, we will highlight novel strategies that could be used to modulate ncRNAs and circumvent ABC transporter-mediated MDR. • Non-coding RNAs (ncRNAs) play pivotal roles in ABC transporter-mediated MDR. • This review updates the induction of ABC transporters by aberrant ncRNA regulation. • Circulating ncRNAs are novel biomarkers for predicting chemotherapy response. • Alternative mRNA polyadenylation intersects with microRNA-mediated transporter regulation. • Novel strategies to modulate ncRNAs and their delivery systems are discussed. [ABSTRACT FROM AUTHOR]

• NcRNAs play potential roles in metabolic reprogramming of macrophages. • Tumor-associated macrophages- and tumor-derived ncRNAs regulate metabolism in tumor-associated macrophages and tumor cells. • NcRNAs reshape the phenotype and function of macrophages via metabolic reprogramming, leading to the development of cancer. Macrophages are the most common immune cells in the tumor microenvironment, and tumor-associated macrophages play an important role in cancer development. Metabolic reprogramming is important for the functional plasticity of macrophages. Studies investigating the relevance of non-coding RNAs (ncRNAs) in human cancer found that ncRNAs can regulate the metabolism of cancer cells and tumor-associated macrophages. NcRNAs include short ncRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs). The most common short ncRNAs are microRNAs, which regulate glucose, lipid, and amino acid metabolism in macrophages by acting on metabolism-related pathways and targeting metabolism-related enzymes and proteins, and are therefore involved in cancer progression. The role of lncRNAs and circRNAs in the metabolism of tumor-associated macrophages remains unclear. LncRNAs affect the glucose metabolism of macrophages, whereas their role in lipid and amino acid metabolism is not clear. CircRNAs regulate amino acid metabolism in macrophages. The roles of ncRNAs in energy metabolism and the underlying mechanisms need to be investigated further. Here, we summarize recent findings on the involvement of ncRNAs in metabolic reprogramming in tumor-associated macrophages, which affect the tumor microenvironment and play important roles in the development of cancer. Improving our understanding of the effects of ncRNAs on metabolic reprogramming of tumor-associated macrophages may facilitate the development of effective clinical therapies. [ABSTRACT FROM AUTHOR]

• The importance of androgen receptors in prostate cancer. • Application of ncRNAs in the diagnosis and treatment of prostate cancer. • Relationship between ncRNAs and androgen receptor signaling pathways. Prostate cancer (PCa) is one of the most common malignancies for men worldwide, and abnormal activation of the androgen receptor (AR) signaling plays an important role in the progression of PCa. However, in the androgen deprivation therapy (ADT), AR signaling inevitably recovered, as a result, exploring novel regulating mechanisms is of great importance. Recently, non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, circular RNAs, could be involved in the progression of PCa, and participate in the regulatory network of AR signaling in a variety of ways. This will help to identify novel molecular mechanisms to promote the development of PCa and find new potential therapeutic targets. In this review, we provide a synopsis of the latest research relating to ncRNAs and associated AR signaling in PCa. [ABSTRACT FROM AUTHOR]