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Infertility is a global problem being associated with emotional and financial burden. Recent studies have shown contribution of a group of non-coding RNAs, namely circular RNAs (circRNAs) to the etiology of some infertility conditions. CircRNA are transcribed from exons and form a circular RNA molecule, being abundant in eukaryotes. Traditionally classified as non-coding RNA, these transcripts are endogenously produced through either non-canonical back-splicing or linear splicing, typically produced from precursor messenger ribonucleic acid (pre-mRNA). While during the canonical splicing process the 3' end of the exon is joined to the 5' end of the succeeding exon to form linear mRNA, during backsplicing, the 3' end to the 5' end of the same exon is joined to make a circular molecule. circRNAs are involved in the regulation of several aspects of spermatogenesis. They appear to influence how stem germ cells grow and divide during the sperm production process. Malfunctions in circRNA activity could contribute to male infertility issues stemming from abnormalities in spermatogenesis. In the current review, we highlight the exciting potential of circRNAs as key players in the male fertility. [ABSTRACT FROM AUTHOR]

This paper provides an exhaustive overview of the intricate interplay between microRNAs (miRNAs) and autophagy in the context of human cancers, underscoring the pivotal role these non-coding RNAs play in modulating autophagic pathways and their implications for cancer development, progression, and resistance to therapy. MiRNAs, as critical regulators of gene expression post-transcription, influence various biological processes, including autophagy, a catabolic mechanism essential for cellular homeostasis, stress response, and survival. The review meticulously delineates the mechanisms through which miRNAs impact autophagy by targeting specific genes and signaling pathways, thereby affecting cancer cell proliferation, metastasis, and response to chemotherapy. It highlights several miRNAs with dual roles, acting either as oncogenes or tumor suppressors based on the cellular context and the specific autophagic pathways they regulate. The paper further explores the therapeutic potential of targeting miRNA-autophagy axis, offering insights into novel strategies for cancer treatment through modulation of this axis. Emphasizing the complexity of the miRNA-autophagy relationship, the review calls for more in-depth studies to unravel the nuanced regulatory networks between miRNAs and autophagy in cancer, which could pave the way for the development of innovative therapeutic interventions and diagnostic tools. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have emerged as significant players in diverse cellular processes, including cell differentiation. Advancements in computational methodologies have facilitated the prediction of lncRNA functions, enabling insights even in non-model organisms like pathogenic parasites, in roles such as parasite development, antigenic variation, and epigenetics. In this work, we focus on the apicomplexan Toxoplasma gondii differentiation process, where the infective stage, tachyzoite, can develop into the cysted stage, bradyzoite, under stress conditions. Using a publicly available transcriptome dataset, we predicted putative lncRNA sequences associated with this differentiation process. Notably, a substantial proportion of these putative lncRNAs exhibited stage-specific expression, particularly at the bradyzoite stage. Furthermore, co-expression patterns between coding transcripts and putative TglncRNAs suggest their involvement in shared processes, such as bradyzoite development. Putative TglncRNA loci analysis revealed their potential influence on the expression of nearby coding genes, including subtelomeric genes unique to the T. gondii genome. Finally we propose a k-mer analysis approach to predict putative functional relationships between characterized lncRNAs from model organisms like Homo sapiens and the putative T. gondii lncRNAs. Our perspective led to predict putative T. gondii lncRNA that potentially could act mediating DNA damage repair pathways, opening a new study field to validate this kind of adaptive mechanisms of T. gondii in response to stress conditions. [ABSTRACT FROM AUTHOR]

The non-coding RNAs (ncRNAs) comprise a large part of human genome that mainly do not code for proteins. Although ncRNAs were first believed to be non-functional, the more investigations highlighted tthe possibility of ncRNAs in controlling vital biological processes. The length of long non-coding RNAs (lncRNAs) exceeds 200 nucleotidesand can be present in nucleus and cytoplasm. LncRNAs do not translate to proteins and they have been implicated in the regulation of tumorigenesis. On the other hand, One way cells die is by a process called autophagy, which breaks down proteins and other components in the cytoplasm., while the aberrant activation of autophagy allegedly involved in the pathogenesis of diseases. The autophagy exerts anti-cancer activity in pre-cancerous lesions, while it has oncogenic function in advanced stages of cancers. The current overview focuses on the connection between lncRNAs and autophagy in urological cancers is discussed. Notably, one possible role for lncRNAs is as diagnostic and prognostic variablesin urological cancers. The proliferation, metastasis, apoptosis and therapy response in prostate, bladder and renal cancers are regulated by lncRNAs. The changes in autophagy levels can also influence the apoptosis, proliferation and therapy response in urological tumors. Since lncRNAs have modulatory functions, they can affect autophagy mechanism to determine progression of urological cancers. [ABSTRACT FROM AUTHOR]

The increasing salinity of agricultural lands highlights the urgent need to improve salt tolerance in crops, a critical factor for ensuring food security. Epigenetic mechanisms are pivotal in plant adaptation to salt stress. This review elucidates the complex roles of DNA methylation, histone modifications, histone variants, and non-coding RNAs in the fine-tuning of gene expression in response to salt stress. It emphasizes how heritable changes, which do not alter the DNA sequence but significantly impact plant phenotype, contribute to this adaptation. DNA methylation is notably prevalent under high-salinity conditions and is associated with changes in gene expression that enhance plant resilience to salt. Modifications in histones, including both methylation and acetylation, are directly linked to the regulation of salt-tolerance genes. The presence of histone variants, such as H2A.Z, is altered under salt stress, promoting plant adaptation to high-salinity environments. Additionally, non-coding RNAs, such as miRNAs and lncRNAs, contribute to the intricate gene regulatory network under salt stress. This review also underscores the importance of understanding these epigenetic changes in developing plant stress memory and enhancing stress tolerance. [ABSTRACT FROM AUTHOR]

Cachexia is a late consequence of various diseases that is characterized by systemic muscle loss, with or without fat loss, leading to significant mortality. Multiple signaling pathways and molecules that increase catabolism, decrease anabolism, and interfere with muscle regeneration are activated. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play vital roles in cachexia muscle atrophy. This review mainly provides the mechanisms of specific ncRNAs to regulate muscle loss during cachexia and discusses the role of ncRNAs in cachectic biomarkers and novel therapeutic strategies that could offer new insights for clinical practice. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC), characterized by high invasiveness, is associated with poor prognosis and elevated mortality rates. Despite the development of effective therapeutic targets for TNBC, systemic chemotherapy and radiotherapy (RdT) remain prevalent treatment modalities. One notable challenge of RdT is the acquisition of radioresistance, which poses a significant obstacle in achieving optimal treatment response. Compelling evidence implicates non-coding RNAs (ncRNAs), gene expression regulators, in the development of radioresistance. This systematic review focuses on describing the role, association, and/or involvement of ncRNAs in modulating radioresponse in TNBC. In adhrence to the PRISMA guidelines, an extensive and comprehensive search was conducted across four databases using carefully selected entry terms. Following the evaluation of the studies based on predefined inclusion and exclusion criteria, a refined selection of 37 original research articles published up to October 2023 was obtained. In total, 33 different ncRNAs, including lncRNAs, miRNAs, and circRNAs, were identified to be associated with radiation response impacting diverse molecular mechanisms, primarily the regulation of cell death and DNA damage repair. The findings highlighted in this review demonstrate the critical roles and the intricate network of ncRNAs that significantly modulates TNBC's responsiveness to radiation. The understanding of these underlying mechanisms offers potential for the early identification of non-responders and patients prone to radioresistance during RdT, ultimately improving TNBC survival outcomes. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a group of small non-coding RNAs and play an important role in controlling vital biological processes, including cell cycle control, apoptosis, metabolism, and development and differentiation, which lead to various diseases such as neurological, metabolic disorders, and cancer. Chemotherapy consider as gold treatment approaches for cancer patients. However, chemotherapeutic is one of the main challenges in cancer management. Doxorubicin (DOX) is an anti-cancer drug that interferes with the growth and spread of cancer cells. DOX is used to treat various types of cancer, including breast, nervous tissue, bladder, stomach, ovary, thyroid, lung, bone, muscle, joint and soft tissue cancers. Also recently, miRNAs have been identified as master regulators of specific genes responsible for the mechanisms that initiate chemical resistance. miRNAs have a regulatory effect on chemotherapy resistance through the regulation of apoptosis process. Also, the effect of miRNAs p53 gene as a key tumor suppressor was confirmed via studies. miRNAs can affect main biological pathways include PI3K pathway. This review aimed to present the current understanding of the mechanisms and effects of miRNAs on apoptosis, p53 and PTEN/PI3K/Akt signaling pathway related to DOX resistance. miRNAs involve in DOX resistance according to effecting pathways. [ABSTRACT FROM AUTHOR]

Bladder cancer (BCa) is a highly prevalent type of cancer worldwide, and it is responsible for numerous deaths and cases of disease. Due to the diverse nature of this disease, it is necessary to conduct significant research that delves deeper into the molecular aspects, to potentially discover novel diagnostic and therapeutic approaches. Lately, there has been a significant increase in the focus on non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), due to their growing recognition for their involvement in the progression and manifestation of BCa. The interest in exosomes has greatly grown due to their potential for transporting a diverse array of active substances, including proteins, nucleic acids, carbohydrates, and lipids. The combination of these components differs based on the specific cell and its condition. Research indicates that using exosomes could have considerable advantages in identifying and forecasting BCa, offering a less invasive alternative. The distinctive arrangement of the lipid bilayer membrane found in exosomes is what makes them particularly effective for administering treatments aimed at managing cancer. In this review, we have tried to summarize different ncRNAs that are involved in BCa pathogenesis. Moreover, we highlighted the role of exosomal ncRNAs in BCa. [ABSTRACT FROM AUTHOR]

Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), are unique RNA molecules widely identified in the eukaryotic genome. Their dysregulation has been discovered and played key roles in the pathogenesis of numerous diseases, including various cancers. Previously considered devoid of protein-coding ability, recent research has revealed that a small number of open reading frames (ORFs) within these ncRNAs endow them with the potential for protein coding. These ncRNAs-derived peptides or proteins have been proven to regulate various physiological and pathological processes through diverse mechanisms. Their emerging roles in disease diagnosis and targeted therapy underscore their potential utility in clinical settings. This comprehensive review aims to provide a systematic overview of proteins or peptides encoded by lncRNAs and circRNAs, elucidate their production and functional mechanisms, and explore their promising applications in cancer diagnosis, disease prediction, and targeted therapy. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) serves as one of the key adjuvant treatments in management of breast cancer. Nevertheless, RT has two major problems: side effects and radioresistance. Given that patients respond differently to RT, it is imperative to understand the molecular mechanisms underlying these differences. Two-thirds of human genes do not encode proteins, as we have realized from genome-scale studies conducted after the advent of the genomic era; nevertheless, molecular understanding of breast cancer to date has been attained almost entirely based on protein-coding genes and their pathways. Long non-coding RNAs (lncRNAs) are a poorly understood but abundant class of human genes that yield functional non-protein-coding RNA transcripts. Here, we canvass the field to seek evidence for the hypothesis that lncRNAs contribute to radioresistance in breast cancer. RT-responsive lncRNAs ranging from "classical" lncRNAs discovered at the dawn of the post-genomic era (such as HOTAIR, NEAT1, and CCAT), to long intergenic lncRNAs such as LINC00511 and LINC02582, antisense lncRNAs such as AFAPAS1 and FGD5-AS1, and pseudogene transcripts such as DUXAP8 were found during our screen of the literature. Radiation-related pathways modulated by these lncRNAs include DNA damage repair, cell cycle, cancer stem cells phenotype and apoptosis. Thus, providing a clear picture of these lncRNAs' underlying RT-relevant molecular mechanisms should help improve overall survival and optimize the best radiation dose for each individual patient. Moreover, in healthy humans, lncRNAs show greater natural expression variation than protein-coding genes, even across individuals, alluding to their exceptional potential for targeting in truly personalized, precision medicine. [ABSTRACT FROM AUTHOR]

Nuclear bodies are structures in eukaryotic cells that lack a plasma membrane and are considered protein condensates, DNA, or RNA molecules. Known nuclear bodies include the nucleolus, Cajal bodies, and promyelocytic leukemia nuclear bodies. These bodies are involved in the concentration, exclusion, sequestration, assembly, modification, and recycling of specific components involved in the regulation of ribosome biogenesis, RNA transcription, and RNA processing. Additionally, nuclear bodies have been shown to participate in cellular processes such as the regulation of transcription of the cell cycle, mitosis, apoptosis, and the cellular stress response. The dynamics and functions of these bodies depend on the state of the cell. It is now known that both DNA and RNA viruses can direct their proteins to nuclear bodies, causing alterations in their composition, dynamics, and functions. Although many of these mechanisms are still under investigation, it is well known that the interaction between viral and nuclear body proteins is necessary for the success of the viral infection cycle. In this review, we concisely describe the interaction between viral and nuclear body proteins. Furthermore, we focus on the role of the nucleolus in RNA virus infections. Finally, we discuss the possible implications of the interaction of viral proteins on cellular transcription and the formation/degradation of non-coding RNAs. [ABSTRACT FROM AUTHOR]

The progressive degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) is accompanied by the formation of a broad array of cytoplasmic and nuclear neuronal inclusions (protein aggregates) largely containing RNA-binding proteins such as TAR DNA-binding protein 43 (TDP-43) or fused in sarcoma/translocated in liposarcoma (FUS/TLS). This process is driven by a liquid-to-solid phase separation generally from proteins in membrane-less organelles giving rise to pathological biomolecular condensates. The formation of these protein aggregates suggests a fundamental alteration in the mRNA expression or the levels of the proteins involved. Considering the role of the epigenome in gene expression, alterations in DNA methylation, histone modifications, chromatin remodeling, non-coding RNAs, and RNA modifications become highly relevant to understanding how this pathological process takes effect. In this review, we explore the evidence that links epigenetic mechanisms with the formation of protein aggregates in ALS. We propose that a greater understanding of the role of the epigenome and how this inter-relates with the formation of pathological LLPS in ALS will provide an attractive therapeutic target. [ABSTRACT FROM AUTHOR]

Ferroptosis, a unique type of regulated cell death plays a vital role in inhibiting tumour malignancy and has presented new opportunities for treatment of therapy in hepatocellular carcinoma. Accumulating studies indicate that epigenetic modifications by non-coding RNAs, including microRNAs, long noncoding RNAs, and circular RNAs, can determine cancer cell vulnerability to ferroptosis in HCC. The present review first summarize the updated core molecular mechanisms of ferroptosis. We then provide a concised overview of epigenetic modification of ferroptosis in HCC. Finally, we review the recent progress in understanding of the ncRNA-mediated regulated mechanisms on ferroptosis in HCC. The review will promote our understanding of the ncRNA-mediated epigenetic regulatory mechanisms modulating ferroptosis in malignancy of HCC, highlighting a novel strategies for treatment of HCC through targeting ncRNA-ferroptosis axis. [ABSTRACT FROM AUTHOR]

Non-coding RNAs (ncRNAs) are transcripts originating from the genome that do not serve as templates for protein synthesis. They function as epigenetic and translational regulators in various pathophysiological mechanisms, including cell proliferation and apoptosis. The ferroptosis signaling pathway, a novel mode of cell death, participates in numerous pathophysiological processes. Its signaling transmission is both complex and precise, featuring interconnected and interdependent pathways. Recent studies suggest that ncRNAs can finely regulate key genes in the ferroptosis pathway, thus modulating cellular functions, reducing oxidative stress, and maintaining maternal-fetal interface homeostasis. Future strategies targeting the ncRNA/ferroptosis axis may provide new perspectives and potential intervention points for treating preeclampsia. This article clarifies how the ncRNA/ferroptosis axis impacts preeclampsia, revealing how ncRNAs interact with ferroptosis, and pinpointing new molecular targets for the treatment of preeclampsia, thereby providing theoretical support for clinical strategies. [ABSTRACT FROM AUTHOR]

The human genome is highly dynamic and only a small fraction of it codes for proteins, but most of the genome is transcribed, highlighting the importance of non-coding RNAs on cellular functions. In addition, it is now known the generation of non-coding RNA fragments under particular cellular conditions and their functions have revealed unexpected mechanisms of action, converging, in some cases, with the biogenic pathways and action machineries of microRNAs or Piwi-interacting RNAs. This led us to the question why the cell produces so many apparently redundant molecules to exert similar functions and regulate apparently convergent processes? However, non-coding RNAs fragments can also function similarly to aptamers, with secondary and tertiary conformations determining their functions. In the present work, it was reviewed and analyzed the current information about the non-coding RNAs fragments, describing their structure and biogenic pathways, with special emphasis on their cellular functions. [ABSTRACT FROM AUTHOR]

Infertility is a complex condition caused by a combination of genetic, environmental, and lifestyle factors. Recent advances in epigenetics have highlighted the importance of epigenetic changes in fertility regulation. This review aims to provide a comprehensive overview of the epigenetic mechanisms involved in infertility, with a focus on DNA methylation, histone modification, and non-coding RNAs. We investigate the specific epigenetic events that occur during gametogenesis, with a focus on spermatogenesis and oogenesis as distinct processes. Furthermore, we investigate how environmental factors such as diet, stress, and toxin exposure can influence these epigenetic changes, potentially leading to infertility. The second part of the review explores epigenetic changes as therapeutic targets for infertility. Emerging therapies that modulate epigenetic marks present promising opportunities for fertility restoration, particularly in spermatogenesis. By summarizing current research findings, this review emphasizes the importance of understanding epigenetic contributions to infertility. Our discussion aims to lay the groundwork for future research directions and clinical applications in reproductive health. [ABSTRACT FROM AUTHOR]

Sepsis is an insidious and frequent condition of severe inflammation due to infections. Several biomarkers have been established for initial screening, but the non-specific nature of the existing biomarkers has led to the investigation of more sensitive and specific tools, such as microRNAs (miRs). These non-coding RNAs are involved in several diseases, including sepsis, due to their roles in cellular homeostasis. Herein, a literature overview was attempted to distinguish the most prominent miRs identified in septic conditions and their usefulness in diagnosis, prognosis and even classification of sepsis. miRs implicated in the regulation of pro and anti-inflammatory mechanisms, such as MIR-146a, MIR-155, MIR-181b, MIR-223-5p, MIR-494-3p, MIR-2055b, MIR-150 and MIR-143 have been pinpointed as acceptable testing tools. Furthermore, the use of miRs as screening panels, specific for septic parameters, such as type of causal infection, inflammation immune pathways affected (NF-kB, STAT/JACK), organs inflicted, as well as parallel screening of certain miRs alongside other long non-coding RNAs (LNCs), as co-regulators of sepsis progression. Overall, miRs exhibit benefits in terms of specificity and sensitivity, as well as practical ease of use and test stability. Furthermore, miRs could offer valuable insights into the molecular basis of disease causality and provide valuable therapeutic information. [ABSTRACT FROM AUTHOR]

The ovary is a major determinant of female reproductive health. Ovarian functions are mainly related to the primordial follicle pool, which is gradually lost with aging. Ovarian aging and reproductive dysfunctions share oxidative stress as a common underlying mechanism. ROS signaling is essential for normal ovarian processes, yet it can contribute to various ovarian disorders when disrupted. Therefore, balance in the redox system is crucial for proper ovarian functions. In the present study, by focusing on mRNAs and ncRNAs described in the ovary and taking into account only validated ncRNA interactions, we built an ovarian antioxidant ceRNA network, named OvAnOx ceRNA, composed of 5 mRNAs (SOD1, SOD2, CAT, PRDX3, GR), 10 miRNAs and 5 lncRNAs (XIST, FGD5-AS1, MALAT1, NEAT1, SNHG1). Our bioinformatic analysis indicated that the components of OvAnOx ceRNA not only contribute to antioxidant defense but are also involved in other ovarian functions. Indeed, antioxidant enzymes encoded by mRNAs of OvAnOx ceRNA operate within a regulatory network that impacts ovarian reserve, follicular dynamics, and oocyte maturation in normal and pathological conditions. The OvAnOx ceRNA network represents a promising tool to unravel the complex dialog between redox potential and ovarian signaling pathways involved in reproductive health, aging, and diseases. [ABSTRACT FROM AUTHOR]

Abstract Infertility is a global problem being associated with emotional and financial burden. Recent studies have shown contribution of a group of non-coding RNAs, namely circular RNAs (circRNAs) to the etiology of some infertility conditions. CircRNA are transcribed from exons and form a circular RNA molecule, being abundant in eukaryotes. Traditionally classified as non-coding RNA, these transcripts are endogenously produced through either non-canonical back-splicing or linear splicing, typically produced from precursor messenger ribonucleic acid (pre-mRNA). While during the canonical splicing process the 3’ end of the exon is joined to the 5’ end of the succeeding exon to form linear mRNA, during backsplicing, the 3’ end to the 5’ end of the same exon is joined to make a circular molecule. circRNAs are involved in the regulation of several aspects of spermatogenesis. They appear to influence how stem germ cells grow and divide during the sperm production process. Malfunctions in circRNA activity could contribute to male infertility issues stemming from abnormalities in spermatogenesis. In the current review, we highlight the exciting potential of circRNAs as key players in the male fertility.

Abstract Long non-coding RNAs (lncRNAs) have emerged as significant players in diverse cellular processes, including cell differentiation. Advancements in computational methodologies have facilitated the prediction of lncRNA functions, enabling insights even in non-model organisms like pathogenic parasites, in roles such as parasite development, antigenic variation, and epigenetics. In this work, we focus on the apicomplexan Toxoplasma gondii differentiation process, where the infective stage, tachyzoite, can develop into the cysted stage, bradyzoite, under stress conditions. Using a publicly available transcriptome dataset, we predicted putative lncRNA sequences associated with this differentiation process. Notably, a substantial proportion of these putative lncRNAs exhibited stage-specific expression, particularly at the bradyzoite stage. Furthermore, co-expression patterns between coding transcripts and putative TglncRNAs suggest their involvement in shared processes, such as bradyzoite development. Putative TglncRNA loci analysis revealed their potential influence on the expression of nearby coding genes, including subtelomeric genes unique to the T. gondii genome. Finally we propose a k-mer analysis approach to predict putative functional relationships between characterized lncRNAs from model organisms like Homo sapiens and the putative T. gondii lncRNAs. Our perspective led to predict putative T. gondii lncRNA that potentially could act mediating DNA damage repair pathways, opening a new study field to validate this kind of adaptive mechanisms of T. gondii in response to stress conditions.

Abstract This paper provides an exhaustive overview of the intricate interplay between microRNAs (miRNAs) and autophagy in the context of human cancers, underscoring the pivotal role these non-coding RNAs play in modulating autophagic pathways and their implications for cancer development, progression, and resistance to therapy. MiRNAs, as critical regulators of gene expression post-transcription, influence various biological processes, including autophagy, a catabolic mechanism essential for cellular homeostasis, stress response, and survival. The review meticulously delineates the mechanisms through which miRNAs impact autophagy by targeting specific genes and signaling pathways, thereby affecting cancer cell proliferation, metastasis, and response to chemotherapy. It highlights several miRNAs with dual roles, acting either as oncogenes or tumor suppressors based on the cellular context and the specific autophagic pathways they regulate. The paper further explores the therapeutic potential of targeting miRNA-autophagy axis, offering insights into novel strategies for cancer treatment through modulation of this axis. Emphasizing the complexity of the miRNA-autophagy relationship, the review calls for more in-depth studies to unravel the nuanced regulatory networks between miRNAs and autophagy in cancer, which could pave the way for the development of innovative therapeutic interventions and diagnostic tools.

Qiang Shao,1,2,* Ying Zhang,2,* Zhiyuan Zhang,2 Wei Jiang,2 Yongcheng Yin,3 Yuepeng Fang,1 Ce Zhang,1 Qingfa Chen,2 Bin Ning1,2 1Cheeloo College of Medicine, Jinan Central Hospital, Shandong University, Jinan, People’s Republic of China; 2Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Ning; Qingfa Chen, Central Hospital Affiliated to Shandong First Medical University, No. 105, Jiefang Road, Jinan, Shandong, 250013, People’s Republic of China, Tel +86-18866510349, Email bning@sdfmu.edu.cn; tsingfachan@163.comBackground: Post-spinal cord injury (SCI) inflammation correlates with neurologic recovery. Through sequencing, we explored the roles of a differentially expressed circRNA in mice after SCI, circGla, on inflammation and recovery of SCI.Methods: The T8–T10 SCI model was established in C57BL6 mice. HE staining and RT-qPCR verified circGla upregulation results after injury obtained through sequencing. RNase R digestion and primer amplification experiments confirmed the circular properties of circGla. Nucleus and cytoplasm isolation experiments and FISH confirmed circGla expression in the astrocyte cytoplasm. AAV was used to establish a circGla knockdown mouse model. Behavioral tests were conducted to assess the recovery of the neurological function. The key inflammatory molecules after SCI were evaluated through MRI, RT-qPCR, and ELISA. For in vitro experiments, circGla was upregulated or knocked down in mouse astrocytes to detect its effect. The binding between miR-488 and circGla was confirmed through RIP and the dual luciferase experiment. RT-qPCR and ELISA confirmed the content correlation of the two molecules and the in vitro inflammatory function of miR-488. The binding experiment in astrocytes confirmed the binding between miR-488 and MEKK1 mRNA. Western blotting of MAPK pathway-related proteins confirmed that MEKK1 is a downstream effector for circGla and miR-488 in astrocytes.Results: Following SCI, the circular RNA circGla levels increased and it existed in the astrocyte cytoplasm. circGla knockdown reduced inflammation and improved neurological recovery in vivo. The correlation between circGla and proinflammatory factors was confirmed in vitro. circGla bound to miR-488, and the high miR-488 level was associated with the low astrocyte inflammatory state. miR-488 bound to MEKK1 mRNA, and upregulation or knockdown of circGla or miR-488 affected MAPK pathway-related protein expression.Conclusion: Following SCI, downregulation of circGla expression in astrocytes can reduce inflammatory manifestations and stimulate long-term functional recovery in mice through miR-488 and MEKK1. Keywords: non-coding RNAs, inflammation, competing endogenous RNAs, traumatic spinal cord injury, secondary injury

Abstract Triple-negative breast cancer (TNBC), characterized by high invasiveness, is associated with poor prognosis and elevated mortality rates. Despite the development of effective therapeutic targets for TNBC, systemic chemotherapy and radiotherapy (RdT) remain prevalent treatment modalities. One notable challenge of RdT is the acquisition of radioresistance, which poses a significant obstacle in achieving optimal treatment response. Compelling evidence implicates non-coding RNAs (ncRNAs), gene expression regulators, in the development of radioresistance. This systematic review focuses on describing the role, association, and/or involvement of ncRNAs in modulating radioresponse in TNBC. In adhrence to the PRISMA guidelines, an extensive and comprehensive search was conducted across four databases using carefully selected entry terms. Following the evaluation of the studies based on predefined inclusion and exclusion criteria, a refined selection of 37 original research articles published up to October 2023 was obtained. In total, 33 different ncRNAs, including lncRNAs, miRNAs, and circRNAs, were identified to be associated with radiation response impacting diverse molecular mechanisms, primarily the regulation of cell death and DNA damage repair. The findings highlighted in this review demonstrate the critical roles and the intricate network of ncRNAs that significantly modulates TNBC's responsiveness to radiation. The understanding of these underlying mechanisms offers potential for the early identification of non-responders and patients prone to radioresistance during RdT, ultimately improving TNBC survival outcomes. Graphical Abstract

Abstract Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), are unique RNA molecules widely identified in the eukaryotic genome. Their dysregulation has been discovered and played key roles in the pathogenesis of numerous diseases, including various cancers. Previously considered devoid of protein-coding ability, recent research has revealed that a small number of open reading frames (ORFs) within these ncRNAs endow them with the potential for protein coding. These ncRNAs-derived peptides or proteins have been proven to regulate various physiological and pathological processes through diverse mechanisms. Their emerging roles in disease diagnosis and targeted therapy underscore their potential utility in clinical settings. This comprehensive review aims to provide a systematic overview of proteins or peptides encoded by lncRNAs and circRNAs, elucidate their production and functional mechanisms, and explore their promising applications in cancer diagnosis, disease prediction, and targeted therapy.

Abstract Ferroptosis, a unique type of regulated cell death plays a vital role in inhibiting tumour malignancy and has presented new opportunities for treatment of therapy in hepatocellular carcinoma. Accumulating studies indicate that epigenetic modifications by non-coding RNAs, including microRNAs, long noncoding RNAs, and circular RNAs, can determine cancer cell vulnerability to ferroptosis in HCC. The present review first summarize the updated core molecular mechanisms of ferroptosis. We then provide a concised overview of epigenetic modification of ferroptosis in HCC. Finally, we review the recent progress in understanding of the ncRNA-mediated regulated mechanisms on ferroptosis in HCC. The review will promote our understanding of the ncRNA-mediated epigenetic regulatory mechanisms modulating ferroptosis in malignancy of HCC, highlighting a novel strategies for treatment of HCC through targeting ncRNA-ferroptosis axis.

Cancer progression results from the dysregulation of molecular pathways, each with unique features that can either promote or inhibit tumor growth. The complexity of carcinogenesis makes it challenging for researchers to target all pathways in cancer therapy, emphasizing the importance of focusing on specific pathways for targeted treatment. One such pathway is the PI3K/Akt pathway, which is often overexpressed in cancer. As tumor cells progress, the expression of PI3K/Akt increases, further driving cancer advancement. This study aims to explore how ncRNAs regulate the expression of PI3K/Akt. NcRNAs are found in both the cytoplasm and nucleus, and their functions vary depending on their location. They can bind to the promoters of PI3K or Akt, either reducing or increasing their expression, thus influencing tumorigenesis. The ncRNA/PI3K/Akt axis plays a crucial role in determining cell proliferation, metastasis, epithelial-mesenchymal transition (EMT), and even chemoresistance and radioresistance in human cancers. Anti-tumor compounds can target ncRNAs to modulate the PI3K/Akt axis. Moreover, ncRNAs can regulate the PI3K/Akt pathway both directly and indirectly.

Acute ischemic stroke is a clinical emergency and a condition with high morbidity, mortality, and disability. Accurate predictive, diagnostic, and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined. With innovations in high-throughput gene sequencing analysis, many aberrantly expressed non-coding RNAs (ncRNAs) in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models. Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes, leading to neuroprotection or deterioration, thus ncRNAs can serve as therapeutic targets in acute ischemic stroke. Moreover, distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. In particular, ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke. In this review, we consolidate the latest progress of research into the roles of ncRNAs (microRNAs, long ncRNAs, and circular RNAs) in the pathological processes of acute ischemic stroke–induced brain damage, as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Prostate cancer (PCa) has the highest frequency of diagnosis among solid tumors and ranks second as the primary cause of cancer-related deaths. Non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs and circular RNAs, frequently exhibit dysregulation and substantially impact the biological behavior of PCa. Compared with circulating ncRNAs, ncRNAs loaded into exosomes are more stable because of protection by the lipid bilayer. Furthermore, exosomal ncRNAs facilitate the intercellular transfer of molecules and information. Increasing evidence suggests that exosomal ncRNAs hold promising potential in the progression, diagnosis and prognosis of PCa. This review aims to discuss the functions of exosomal ncRNAs in PCa, evaluate their possible applications as clinical biomarkers and therapeutic targets, and provide a comprehensive overview of the ncRNAs regulatory network in PCa. We also identified ncRNAs that can be utilized as biomarkers for diagnosis, staging, grading and prognosis assessment in PCa. This review offers researchers a fresh perspective on the functions of exosomal ncRNAs in PCa and provides additional options for its diagnosis, progression monitoring, and prognostic prediction.

We analyzed the structure of human long non-coding RNA (lncRNAs) genes to investigate whether the non-coding transcriptome is organized in modular domains, as is the case for protein-coding genes. To this aim, we compared all known human lncRNA exons and identified 340 pairs of exons with high sequence and/or secondary structure similarity but embedded in a dissimilar sequence context. We grouped these pairs in 106 clusters based on their reciprocal similarities. These shared modules are highly conserved between humans and the four great ape species, display evidence of purifying selection and likely arose as a result of recent segmental duplications. Our analysis contributes to the understanding of the mechanisms driving the evolution of the non-coding genome and suggests additional strategies towards deciphering the functional complexity of this class of molecules.

Diabetes mellitus has surged in prevalence, emerging as a prominent epidemic and assuming a foremost position among prevalent medical disorders. Diabetes constitutes a pivotal risk element for cardiovascular maladies, with diabetic cardiomyopathy (DCM) standing out as a substantial complication encountered by individuals with diabetes. Apoptosis represents a physiological phenomenon observed throughout the aging and developmental stages, giving rise to the programmed cell death, which is implicated in DCM. Non-coding RNAs assume significant functions in modulation of gene expression. Their deviant expression of ncRNAs is implicated in overseeing diverse cellular attributes such as proliferation, apoptosis, and has been postulated to play a role in the progression of DCM. Notably, ncRNAs and the process of apoptosis can mutually influence and cooperate in shaping the destiny of human cardiac tissues. Therefore, the exploration of the interplay between apoptosis and non-coding RNAs holds paramount importance in the formulation of efficacious therapeutic and preventive approaches for managing DCM. In this review, we provide a comprehensive overview of the apoptotic signaling pathways relevant to DCM and subsequently delve into the reciprocal regulation between apoptosis and ncRNAs in DCM. These insights contribute to an enhanced comprehension of DCM and the development of therapeutic strategies.

Abstract The development of drug resistance remains a major challenge in cancer treatment. Ferroptosis, a unique type of regulated cell death, plays a pivotal role in inhibiting tumour growth, presenting new opportunities in treating chemotherapeutic resistance. Accumulating studies indicate that epigenetic modifications by non-coding RNAs (ncRNA) can determine cancer cell vulnerability to ferroptosis. In this review, we first summarize the role of chemotherapeutic resistance in cancer growth/development. Then, we summarize the core molecular mechanisms of ferroptosis, its upstream epigenetic regulation, and its downstream effects on chemotherapeutic resistance. Finally, we review recent advances in understanding how ncRNAs regulate ferroptosis and from such modulate chemotherapeutic resistance. This review aims to enhance general understanding of the ncRNA-mediated epigenetic regulatory mechanisms which modulate ferroptosis, highlighting the ncRNA-ferroptosis axis as a key druggable target in overcoming chemotherapeutic resistance.

Abstract Background The yield of major crops is generally limited by sink capacity and source strength. Cucumber is a typical raffinose family oligosaccharides (RFOs)–transporting crop. Non-coding RNAs and alternative polyadenylation (APA) play important roles in the regulation of growth process in plants. However, their roles on the sink‒source regulation have not been demonstrated in RFOs–translocating species. Results Here, whole–transcriptome sequencing was applied to compare the leaves of cucumber under different sink strength, that is, no fruit-carrying leaves (NFNLs) and fruit-carrying leaves (FNLs) at 12th node from the bottom. The results show that 1101 differentially expressed (DE) mRNAs, 79 DE long non–coding RNAs (lncRNAs) and 23 DE miRNAs were identified, which were enriched in photosynthesis, energy production and conversion, plant hormone signal transduction, starch and carbohydrate metabolism and protein synthesis pathways. Potential co–expression networks like, DE lncRNAs–DE mRNAs/ DE miRNAs–DE mRNAs, and competing endogenous RNA (ceRNA) regulation models (DE lncRNAs–DE miRNAs–DE mRNAs) associated with sink‒source allocation, were constructed. Furthermore, 37 and 48 DE genes, which enriched in MAPK signaling and plant hormone signal transduction pathway, exist differentially APA, and SPS (CsaV3_2G033300), GBSS1 (CsaV3_5G001560), ERS1 (CsaV3_7G029600), PNO1 (CsaV3_3G003950) and Myb (CsaV3_3G022290) may be regulated by both ncRNAs and APA between FNLs and NFNLs, speculating that ncRNAs and APA are involved in the regulation of gene expression of cucumber sink‒source carbon partitioning. Conclusions These results reveal a comprehensive network among mRNAs, ncRNAs, and APA in cucumber sink–source relationships. Our findings also provide valuable information for further research on the molecular mechanism of ncRNA and APA to enhance cucumber yield.

Abstract Exosomes mediate cell-to-cell crosstalk involving a variety of biomolecules through an intricate signaling network. In recent years, the pivotal role of exosomes and their non-coding RNAs cargo in the development and progression of several cancer types clearly emerged. In particular, tumor bulk and its microenvironment co-evolve through cellular communications where these nanosized extracellular vesicles are among the most relevant actors. Knowledge about the cellular, and molecular mechanisms involved in these communications will pave the way for novel exosome-based delivery of therapeutic RNAs as well as innovative prognostic/diagnostic tools. Despite the valuable therapeutic potential and clinical relevance of exosomes, their role on sarcoma has been vaguely reported because the rarity and high heterogeneity of this type of cancer. Here, we dissected the scientific literature to unravel the multifaceted role of exosomal non-coding RNAs as mediator of cell-to-cell communications in the sarcoma subtypes.

Ya-ru Liu,1,2,* Jie-Quan Wang,3– 5,* Ling Fang,1,2 Quan Xia1,2 1Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, 230022, People’s Republic of China; 3Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of China; 4Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, 230000, People’s Republic of China; 5Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, 230000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Fang; Quan Xia, Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email fangling@ahmu.edu.cn; xiaquan2010@163.comAbstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease whose precise pathogenesis remains mysterious. The involvement of epigenetic regulation in the pathogenesis of RA is one of the most anticipated findings, among which non-coding RNAs (ncRNAs) hold great application promise as diagnostic and therapeutic biomarkers for RA. Extracellular vesicles (EVs) are a heterogeneous group of nano-sized, membrane-enclosed vesicles that mediate intercellular communication and substance exchange, especially the transfer of ncRNAs from donor cells, thereby regulating the functional activities and biological processes of recipient cells. In light of the significant correlation between EVs, ncRNAs, and RA, we first documented expression levels of EVs and their-encapsulated ncRNAs in RA individuals, and methodically discussed their-implicated signaling pathways and phenotypic changes. The last but not least, we paied special attention to the therapeutic benefits of gene therapy reagents specifically imitating or silencing candidate ncRNAs with exosomes as carriers on RA animal models, and briefly highlighted their clinical application advantage and foreground. In conclusion, the present review may be conducive to a deeper comprehension of the diagnostic and therapeutic roles of EVs-enwrapped ncRNAs in RA, with special emphasis on exosomal ncRNAs, which may offer hints for the monitoring and treatment of RA. Keywords: rheumatoid arthritis, extracellular vesicles, non-coding RNAs, diagnostic and therapeutic role

Co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS) has severely restricted the healthy development of pig breeding. Exploring disease resistance of non-coding RNAs in pigs co-infected with PRRSV and HPS is therefore critical to complement and elucidate the molecular mechanisms of disease resistance in Kele piglets and to innovate the use of local pig germplasm resources in China. RNA-seq of lungs from Kele piglets with single-infection of PRRSV or HPS and co-infection of both pathogens was performed. Two hundred and twenty-five differentially expressed long non-coding RNAs (DElncRNAs) and 30 DEmicroRNAs (DEmiRNAs) were identified and characterized in the PRRSV and HPS co-infection (PRRSV–HPS) group. Compared with the single-infection groups, 146 unique DElncRNAs, 17 unique DEmiRNAs, and 206 target differentially expressed genes (DEGs) were identified in the PRRSV–HPS group. The expression patterns of 20 DEmiRNAs and DElncRNAs confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) were consistent with those determined by high-throughput sequencing. In the PRRSV–HPS group, the target DEGs were enriched in eight immune Gene Ontology terms relating to two unique DEmiRNAs and 16 DElncRNAs, and the unique target DEGs participated the host immune response to pathogens infection by affecting 15 immune-related Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Notably, competitive endogenous RNA (ceRNA) networks of different groups were constructed, and the ssc-miR-671-5p miRNA was validated as a potential regulatory factor to regulate DTX4 and AEBP1 genes to achieve innate antiviral effects and inhibit pulmonary fibrosis by dual-luciferase reporter assays. These results provided insight into further study on the molecular mechanisms of resistance to PRRSV and HPS co-infection in Kele piglets.

Recently, new data have been added to the interaction between non-coding RNAs (ncRNAs) and epigenetic machinery. Epigenetics includes enzymes involved in DNA methylation, histone modifications, and RNA modifications, and mechanisms underlying chromatin structure, repressive states, and active states operating in transcription. The main focus is on long ncRNAs (lncRNAs) acting as scaffolds to assemble protein complexes. This review does not cover RNA’s role in sponging microRNAs, or decoy functions. Several lncRNAs were shown to regulate chromatin activation and repression by interacting with Polycomb repressive complexes and mixed-lineage leukemia (MLL) activating complexes. Various groups reported on enhancer of zeste homolog 2 (EZH2) interactions with regulatory RNAs. Knowledge of the function of these complexes opens the perspective to develop new therapeutics for cancer treatment. Lastly, the interplay between lncRNAs and epitranscriptomic modifications in cancers paves the way for new targets in cancer therapy. The approach to inhibit lncRNAs interaction with protein complexes and perspective to regulate epitrascriptomics-regulated RNAs may bring new compounds as therapeuticals in various types of cancer.

Abstract Background The prevalence of infertility among couples is estimated to range from 8 to 12%. A paradigm shift has occurred in understanding of infertility, challenging the notion that it predominantly affects women. It is now acknowledged that a significant proportion, if not the majority, of infertility cases can be attributed to male-related factors. Various elements contribute to male reproductive impairments, including aberrant sperm production caused by pituitary malfunction, testicular malignancies, aplastic germ cells, varicocele, and environmental factors. Main body The epigenetic profile of mammalian sperm is distinctive and specialized. Various epigenetic factors regulate genes across different levels in sperm, thereby affecting its function. Changes in sperm epigenetics, potentially influenced by factors such as environmental exposures, could contribute to the development of male infertility. Conclusion In conclusion, this review investigates the latest studies pertaining to the mechanisms of epigenetic changes that occur in sperm cells and their association with male reproductive issues.

Bladder cancer (BC) is a highly frequent neoplasm in correlation with significant rate of morbidity, mortality, and cost. The onset of BC is predominantly triggered by environmental and/or occupational exposures to carcinogens, such as tobacco. There are two distinct pathways by which BC can be developed, including non-muscle-invasive papillary tumors (NMIBC) and non-papillary (or solid) muscle-invasive tumors (MIBC). The Cancer Genome Atlas project has further recognized key genetic drivers of MIBC along with its subtypes with particular properties and therapeutic responses; nonetheless, NMIBC is the predominant BC presentation among the suffering individuals. Radical cystoprostatectomy, radiotherapy, and chemotherapy have been verified to be the common therapeutic interventions in metastatic tumors, among which chemotherapeutics are more conventionally utilized. Although multiple chemo drugs have been broadly administered for BC treatment, cisplatin is reportedly the most effective chemo drug against the corresponding malignancy. Notwithstanding, tumor recurrence is usually occurred following the consumption of cisplatin regimens, particularly due to the progression of chemo-resistant trait. In this framework, non-coding RNAs (ncRNAs), as abundant RNA transcripts arise from the human genome, are introduced to serve as crucial contributors to tumor expansion and cisplatin chemo-resistance in bladder neoplasm. In the current review, we first investigated the best-known ncRNAs, i.e. microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), correlated with cisplatin chemo-resistance in BC cells and tissues. We noticed that these ncRNAs could mediate the BC-related cisplatin-resistant phenotype through diverse cellular processes and signaling mechanisms, reviewed here. Eventually, diagnostic and prognostic potential of ncRNAs, as well as their therapeutic capabilities were highlighted in regard to BC management.

Background: The yield of major crops is generally limited by sink capacity and source strength. Cucumber is a typical raffinose family oligosaccharides (RFOs)–transporting crop. Non-coding RNAs and alternative polyadenylation (APA) play important roles in the regulation of growth process in plants. However, their roles on the sink‒source regulation have not been demonstrated in RFOs–translocating species. Results: Here, whole–transcriptome sequencing was applied to compare the leaves of cucumber under different sink strength, that is, no fruit-carrying leaves (NFNLs) and fruit-carrying leaves (FNLs) at 12th node from the bottom. The results show that 1101 differentially expressed (DE) mRNAs, 79 DE long non–coding RNAs (lncRNAs) and 23 DE miRNAs were identified, which were enriched in photosynthesis, energy production and conversion, plant hormone signal transduction, starch and carbohydrate metabolism and protein synthesis pathways. Potential co–expression networks like, DE lncRNAs–DE mRNAs/ DE miRNAs–DE mRNAs, and competing endogenous RNA (ceRNA) regulation models (DE lncRNAs–DE miRNAs–DE mRNAs) associated with sink‒source allocation, were constructed. Furthermore, 37 and 48 DE genes, which enriched in MAPK signaling and plant hormone signal transduction pathway, exist differentially APA, and SPS (CsaV3_2G033300), GBSS1 (CsaV3_5G001560), ERS1 (CsaV3_7G029600), PNO1 (CsaV3_3G003950) and Myb (CsaV3_3G022290) may be regulated by both ncRNAs and APA between FNLs and NFNLs, speculating that ncRNAs and APA are involved in the regulation of gene expression of cucumber sink‒source carbon partitioning. Conclusions: These results reveal a comprehensive network among mRNAs, ncRNAs, and APA in cucumber sink–source relationships. Our findings also provide valuable information for further research on the molecular mechanism of ncRNA and APA to enhance cucumber yield. [ABSTRACT FROM AUTHOR]

Mechanical forces affect periodontal health through multiple mechanisms. Normally, mechanical forces can boost soft and hard tissue metabolism. However, excessive forces may damage the periodontium or result in irreversible inflammation, whereas absence of occlusion forces also leads to tissue atrophy and bone resorption. We systemically searched the PubMed and Web of Science databases and found certain mechanisms of mechanical forces on immune defence, extracellular matrix (ECM) metabolism, specific proteins, bone metabolism, characteristic periodontal ligament stem cells (PDLSCs) and non-coding RNAs (ncRNAs) as these factors contribute to periodontal homeostasis. The immune defence functions change under forces; genes, signalling pathways and proteinases are altered under forces to regulate ECM metabolism; several specific proteins are separately discussed due to their important functions in mechanotransduction and tissue metabolism. Functions of osteocytes, osteoblasts, and osteoclasts are activated to maintain bone homeostasis. Additionally, ncRNAs have the potential to influence gene expression and thereby, modify tissue metabolism. This review summarizes all these mechanisms of mechanical forces on periodontal homeostasis. Identifying the underlying causes, this review provides a new perspective of the mechanisms of force on periodontal health and guides for some new research directions of periodontal homeostasis. [ABSTRACT FROM AUTHOR]

The development of drug resistance remains a major challenge in cancer treatment. Ferroptosis, a unique type of regulated cell death, plays a pivotal role in inhibiting tumour growth, presenting new opportunities in treating chemotherapeutic resistance. Accumulating studies indicate that epigenetic modifications by non-coding RNAs (ncRNA) can determine cancer cell vulnerability to ferroptosis. In this review, we first summarize the role of chemotherapeutic resistance in cancer growth/development. Then, we summarize the core molecular mechanisms of ferroptosis, its upstream epigenetic regulation, and its downstream effects on chemotherapeutic resistance. Finally, we review recent advances in understanding how ncRNAs regulate ferroptosis and from such modulate chemotherapeutic resistance. This review aims to enhance general understanding of the ncRNA-mediated epigenetic regulatory mechanisms which modulate ferroptosis, highlighting the ncRNA-ferroptosis axis as a key druggable target in overcoming chemotherapeutic resistance. [ABSTRACT FROM AUTHOR]

Exosomes mediate cell-to-cell crosstalk involving a variety of biomolecules through an intricate signaling network. In recent years, the pivotal role of exosomes and their non-coding RNAs cargo in the development and progression of several cancer types clearly emerged. In particular, tumor bulk and its microenvironment co-evolve through cellular communications where these nanosized extracellular vesicles are among the most relevant actors. Knowledge about the cellular, and molecular mechanisms involved in these communications will pave the way for novel exosome-based delivery of therapeutic RNAs as well as innovative prognostic/diagnostic tools. Despite the valuable therapeutic potential and clinical relevance of exosomes, their role on sarcoma has been vaguely reported because the rarity and high heterogeneity of this type of cancer. Here, we dissected the scientific literature to unravel the multifaceted role of exosomal non-coding RNAs as mediator of cell-to-cell communications in the sarcoma subtypes. [ABSTRACT FROM AUTHOR]

Ischemic stroke poses a significant global health burden, with rapid revascularization treatments being crucial but often insufficient to mitigate ischemia-reperfusion (I/R) injury. Dexmedetomidine (DEX) has shown promise in reducing cerebral I/R injury, but its potential molecular mechanism, particularly its interaction with non-coding RNAs (ncRNAs), remains unclear. This study investigates DEX's therapeutic effect and potential molecular mechanisms in reducing cerebral I/R injury. A transient middle cerebral artery obstruction (tMACO) model was established to simulate cerebral I/R injury in adult rats. DEX was administered pre-ischemia and post-reperfusion. RNA sequencing and bioinformatic analyses were performed on the ischemic cerebral cortex to identify differentially expressed non-coding RNAs (ncRNAs) and mRNAs. The sequencing results showed 6,494 differentially expressed (DE) mRNA and 2698 DE circRNA between the sham and tMCAO (I/R) groups. Additionally, 1809 DE lncRNA, 763 DE mRNA, and 2795 DE circRNA were identified between the I/R group and tMCAO + DEX (I/R + DEX) groups. Gene ontology (GO) analysis indicated significant enrichment in multicellular biogenesis, plasma membrane components, and protein binding. KEGG analysis further highlighted the potential mechanism of DEX action in reducing cerebral I/R injury, with hub genes involved in inflammatory pathways. This study demonstrates DEX's efficacy in reducing cerebral I/R injury and offers insights into its brain-protective effects, especially in ischemic stroke. Further research is warranted to fully understand DEX's neuroprotective mechanisms and its clinical applications. [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 longterm growth at 32°C compared to those reared at 28°C and 24°C. Nextgeneration 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. [ABSTRACT FROM AUTHOR]

The transition of fibroblasts to myofibroblasts (FMT) represents a pivotal process in wound healing, tissue repair, and fibrotic diseases. This intricate transformation involves dynamic changes in cellular morphology, gene expression, and extracellular matrix remodeling. While extensively studied at the molecular level, recent research has illuminated the regulatory roles of non-coding RNAs (ncRNAs) in orchestrating FMT. This review explores the emerging roles of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating this intricate process. NcRNAs interface with key signaling pathways, transcription factors, and epigenetic mechanisms to fine-tune gene expression during FMT. Their functions are critical in maintaining tissue homeostasis, and disruptions in these regulatory networks have been linked to pathological fibrosis across various tissues. Understanding the dynamic roles of ncRNAs in FMT bears therapeutic promise. Targeting specific ncRNAs holds potential to mitigate exaggerated myofibroblast activation and tissue fibrosis. However, challenges in delivery and specificity of ncRNA-based therapies remain. In summary, ncRNAs emerge as integral regulators in the symphony of FMT, orchestrating the balance between quiescent fibroblasts and activated myofibroblasts. As research advances, these ncRNAs appear to be prospects for innovative therapeutic strategies, offering hope in taming the complexities of fibrosis and restoring tissue equilibrium. [ABSTRACT FROM AUTHOR]

Metastasis is the primary cause of cancer-related death, with the dissemination and colonization of primary tumor cells at the metastatic site facilitated by various molecules and complex pathways. Understanding the biological mechanisms underlying the metastatic process is critical for the development of effective interventions. Several epigenetic modifications have been identified that play critical roles in regulating cancer metastasis. This review aims to provide a comprehensive summary of recent advances in understanding the role of epigenetic modifiers, including histone modifications, DNA methylation, non-coding RNAs, enhancer reprogramming, chromatin accessibility, and N6-methyladenosine, in metastasis-associated processes, such as epithelial-mesenchymal transition (EMT), cancer cell migration, and invasion. In particular, this review provides a detailed and in-depth description of the role of crosstalk between epigenetic regulators in tumor metastasis. Additionally, we explored the potential and limitations of epigenetics-related target molecules in the diagnosis, treatment, and prognosis of cancer metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: Epigenetics plays a significant role in understanding depression, which is considered one of the most complex mental health disorders. Epigenetics includes all changes in gene expression that do not involve any modifications to DNA sequences. In depression, epigenetic changes may affect the activation or suppression of specific genes involved in mood regulation. Scientists have attempted to determine how specific environmental factors, such as stress or trauma, can trigger epigenetic changes that are closely linked to gene function. By studying these mechanisms, researchers have developed effective treatments and interventions for depression. This discovery not only provides a better understanding of the biological basis of depression, but also suggests new approaches for highly personalized treatments that may be available to individuals suffering from this widespread mental health disorder in the near future. Depression, a significant mental health disorder, is under intense research scrutiny to uncover its molecular foundations. Epigenetics, which focuses on controlling gene expression without altering DNA sequences, offers promising avenues for innovative treatment. This review explores the pivotal role of epigenetics in depression, emphasizing two key aspects: (I) identifying epigenetic targets for new antidepressants and (II) using personalized medicine based on distinct epigenetic profiles, highlighting potential epigenetic focal points such as DNA methylation, histone structure alterations, and non-coding RNA molecules such as miRNAs. Variations in DNA methylation in individuals with depression provide opportunities to target genes that are associated with neuroplasticity and synaptic activity. Aberrant histone acetylation may indicate that antidepressant strategies involve enzyme modifications. Modulating miRNA levels can reshape depression-linked gene expression. The second section discusses personalized medicine based on epigenetic profiles. Analyzing these patterns could identify biomarkers associated with treatment response and susceptibility to depression, facilitating tailored treatments and proactive mental health care. Addressing ethical concerns regarding epigenetic information, such as privacy and stigmatization, is crucial in understanding the biological basis of depression. Therefore, researchers must consider these issues when examining the role of epigenetics in mental health disorders. The importance of epigenetics in depression is a critical aspect of modern medical research. These findings hold great potential for novel antidepressant medications and personalized treatments, which would significantly improve patient outcomes, and transform psychiatry. As research progresses, it is expected to uncover more complex aspects of epigenetic processes associated with depression, enhance our comprehension, and increase the effectiveness of therapies. [ABSTRACT FROM AUTHOR]

Electronic cigarette (e-cig) use, otherwise known as "vaping", is widespread among adolescent never-smokers and adult smokers seeking a less-harmful alternative to combustible tobacco products. To date, however, the long-term health consequences of vaping are largely unknown. Many toxicants and carcinogens present in e-cig vapor and tobacco smoke exert their biological effects through epigenetic changes that can cause dysregulation of disease-related genes. Long non-coding RNAs (lncRNAs) have emerged as prime regulators of gene expression in health and disease states. A large body of research has shown that lncRNAs regulate genes involved in the pathogenesis of smoking-associated diseases; however, the utility of lncRNAs for assessing the disease-causing potential of vaping remains to be fully determined. A limited but growing number of studies has shown that lncRNAs mediate dysregulation of disease-related genes in cells and tissues of vapers as well as cells treated in vitro with e-cig aerosol extract. This review article provides an overview of the evolution of e-cig technology, trends in use, and controversies on the safety, efficacy, and health risks or potential benefits of vaping relative to smoking. While highlighting the importance of lncRNAs in cell biology and disease, it summarizes the current and ongoing research on the modulatory effects of lncRNAs on gene regulation and disease pathogenesis in e-cig users and in vitro experimental settings. The gaps in knowledge are identified, priorities for future research are highlighted, and the importance of empirical data for tobacco products regulation and public health is underscored. [ABSTRACT FROM AUTHOR]

The emergence of cancers involves numerous coding and non-coding genes. Understanding the contribution of non-coding RNAs (ncRNAs) to the cancer neighborhood is crucial for interpreting the interaction between molecular markers of cancer. However, there is a lack of systematic studies on the involvement of ncRNAs in the cancer neighborhood. In this paper, we construct an interaction network which encompasses multiple genes. We focus on the fundamental topological indicator, namely connectivity, and evaluate its performance when applied to cancer-affected genes using statistical indices. Our findings reveal that ncRNAs significantly enhance the connectivity of affected genes and mediate the inclusion of more genes in the cancer module. To further explore the role of ncRNAs in the network, we propose a connectivity-based method which leverages the bridging function of ncRNAs across cancer-affected genes and reveals the non-coding RNAs extended omnigenic module (NeOModule). Topologically, this module promotes the formation of cancer patterns involving ncRNAs. Biologically, it is enriched with cancer pathways and treatment targets, providing valuable insights into disease relationships. [ABSTRACT FROM AUTHOR]