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The plant immune system protects against pests and diseases. The recognition of stress-related molecular patterns triggers localised immune responses, which are often followed by longer-lasting systemic priming and/or up-regulation of defences. In some cases, this induced resistance (IR) can be transmitted to following generations. Such transgenerational IR is gradually reversed in the absence of stress at a rate that is proportional to the severity of disease experienced in previous generations. This review outlines the mechanisms by which epigenetic responses to pathogen infection shape the plant immune system across expanding time scales. We review the cis- and trans-acting mechanisms by which stress-inducible epigenetic changes at transposable elements (TEs) regulate genome-wide defence gene expression and draw particular attention to one regulatory model that is supported by recent evidence about the function of AGO1 and H2A.Z in transcriptional control of defence genes. Additionally, we explore how stress-induced mobilisation of epigenetically controlled TEs acts as a catalyst of Darwinian evolution by generating (epi)genetic diversity at environmentally responsive genes. This raises questions about the long-term evolutionary consequences of stress-induced diversification of the plant immune system in relation to the long-held dichotomy between Darwinian and Lamarckian evolution.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting approximately 20% of children and 10% of adults. While previous studies have linked AD to allergen exposure, disruption of the skin barrier, and Type 2 immune responses, the precise pathophysiology of AD remains elusive, significantly limiting the effectiveness of current treatments. Noncoding RNAs (ncRNAs), a diverse group of transcripts that do not encode proteins and account for at least 98% of the human genome, are implicated in numerous physiological and pathological processes. A growing body of evidence underscores the pivotal role of ncRNAs in the pathogenesis and progression of AD. This review offers a detailed synthesis of the latest insights into the involvement of ncRNAs in AD, as well as their potential as diagnostic biomarkers and therapeutic targets.

Recent transcriptome analyses have revealed that noncoding RNAs (ncRNAs) are broadly expressed in mammalian cells and abundant in the CNS, with tissue and cell type-specific expression patterns. Moreover, ncRNAs have been found to intricately and dynamically regulate various signaling pathways in neurodegeneration. As such, some antisense transcripts and microRNAs are known to directly affect neurodegeneration in disease contexts. The functions of ncRNAs in pathogenesis are unique for each disorder, as are the pertinent networks of ncRNA/miRNA/mRNA that mediate these functions. Thus, further understanding of ncRNA biogenesis and effects might aid the discovery of diagnostic biomarkers or development of effective therapeutics for neurodegenerative disorders. Here, we review the ncRNAs that have so far been identified in major neurodegenerative disease etiology and the mechanisms that link ncRNAs with disease-specific phenotypes, such as HTT aggregation in HD, α-synuclein in PD, and Aβ plaques and hyperphosphorylated Tau in AD. We also summarize the known lncRNA/miRNA/mRNA networks that participate in neurodegenerative diseases, and we discuss ncRNA-related treatments shown to delay disease onset and prolong lifespan in rodent models.

Endometriosis is a chronic gynecologic disease that negatively affects the quality of life of many women. Unfortunately, endometriosis does not have a cure. The current medical treatments involve hormonal manipulation with unwanted side effects and high recurrence rates after stopping the medication. Sadly, a definitive diagnosis for endometriosis requires invasive surgical procedures, with the risk of complications, additional surgeries in the future, and a high rate of recurrence. Both improved therapies and noninvasive diagnostic tests are needed. The unique molecular features of endometriosis have been studied at the coding gene level. While the molecular components of endometriosis at the small RNA level have been studied extensively, other noncoding RNAs, such as long intergenic noncoding RNAs and the more recently discovered subset of long noncoding RNAs called circular RNAs, have been studied more limitedly. This review describes the molecular formation of long noncoding and the unique circumstances of the formation of circular long noncoding RNAs, their expression and function in endometriosis, and promising preclinical studies. Continued translational research on long noncoding RNAs, including the more stable circular long noncoding RNAs, may lead to improved therapeutic and diagnostic opportunities.

With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.

The initial identification of long non-coding RNA myocardial infarction associated transcript (MIAT) as a genetic risk factor of myocardial infarction has made this lncRNA (designated as lncR-MIAT here) a focus of intensive studies worldwide. Emerging evidence supports that lncR-MIAT is susceptible in its expression to multiple deleterious factors like angiotensin II, isoproterenol, hypoxia, and infection and is anomaly overexpressed in serum, plasma, blood cells and myocardial tissues under a variety of cardiovascular conditions including myocardial infarction, cardiac hypertrophy, diabetic cardiomyopathy, dilated cardiomyopathy, sepsis cardiomyopathy, atrial fibrillation and microvascular dysfunction. Experimental results consistently demonstrated that upregulation of lncR-MIAT plays active roles in the pathological processes of the cardiovascular system and knockdown of this lncRNA effectively ameliorates the adverse conditions. The available data revealed that lncR-MIAT acts through multiple mechanisms such as competitive endogenous RNA, natural antisense RNA and RNA/protein interactions. Moreover, the functional domains of lncR-MIAT accounting for certain specific cellular functions of the full-length transcript have been identified and characterized. These insights will not only tremendously advance our understanding of lncRNA biology and pathophysiology, but also offer good opportunities for more innovative and precise design of agents that have the potential to be developed into new drugs for better therapy of cardiovascular diseases (CVDs) in the future. Herein, we provide an overview of lncR-MIAT, focusing on its roles in cardiovascular diseases, underline the unique cellular/molecular mechanisms for its actions, and speculate the perspectives about the translational studies on the potential diagnostic and therapeutic applications of lncR-MIAT.

Background/Objectives: Male infertility is a complex condition with various underlying genetic factors. microRNAs (miRNAs) play a crucial role in gene regulation, and their disruption can significantly impact fertility. This study aimed to identify variants within miRNA genes and elucidate their impact on male infertility. Methods: Whole genome sequencing was performed on blood samples from men with asthenozoospermia, oligozoospermia, and teratozoospermia, compared to normozoospermic controls. The analysis revealed a significant number of unique variants in each infertile group. We subsequently focused on variants in miRNA regions, followed by an in silico analysis to investigate the role of the identified variants and miRNAs in male infertility. Results: Focused analysis on miRNA genes identified 19 exclusive variants in teratozoospermic men, 24 in asthenozoospermic, and 27 in oligozoospermic, all mapping to pre-miRNAs or mature miRNAs. Functional analyses using Gene Ontology (GO) and KEGG pathways highlighted key biological processes and pathways disrupted by these variants and miRNA–mRNA interactions, including transcription regulation, signaling, and cancer-related pathways. Furthermore, six variants (rs17797090, rs1844035, rs7210937, rs451887, rs12233076, and rs6787734) were common across the infertile groups, suggesting their importance in male infertility or their potential as biomarkers. Common variants were also validated in another clinically relevant group of men. Some miRNAs with identified variants, such as hsa-miR-449b and hsa-miR-296, have been previously implicated in male infertility and exhibit differential expression between fertile and infertile men, according to the literature, too. Conclusion: These results provide new insights into the genetic basis of male infertility and open avenues for future research and therapeutic interventions.

Background Growing evidences have showed that mucins (MUCs) are linked to occurrence and progression of human cancers. However, a comprehensive study regarding the expression, diagnosis, prognosis and mechanism of MUCs in breast cancer remains absent. Methods: A series of in silico analyses were employed in this study. Results: After performing comprehensive analysis for MUCs, MUC14 was identified as the most potential regulator in breast cancer, with downregulated expression in both mRNA and protein levels and significant diagnostic and prognostic values in breast cancer. Mechanistic exploration revealed that a potential ncRNA-mRNA axis, involving LINC01128/LINC01140/SGMS1-AS1/LINC00667-miR-137/miR-429-BCL2, might be partially responsible for MUC14′s functions in breast cancer. Conclusions: Collectively, our study elucidated a key role of MUC14 in breast cancer and also provided some clues for explanation of the molecular action mechanism of MUC14 in breast cancer.

Formalin-fixed paraffin-embedded (FFPE) tissues are commonly used both clinically and in forensic pathology. Recently, noncoding RNA (ncRNA) has attracted interest among molecular medical researchers. However, it remains unclear whether newly identified ncRNAs, such as long noncoding RNA (lncRNA) and circular RNA (circRNA), remain stable for downstream molecular analysis in FFPE tissues. Here, we assessed the feasibility of using autoptic FFPE brain tissues from eight individuals to perform quantitative molecular analyses. Selected RNA targets (9 mRNAs and 15 ncRNAs) with different amplicon lengths were studied by RT-qPCR in paired fresh and FFPE specimens. For RNA quality assessment, RNA purity and yield were comparable between the two sample cohorts; however, the RNA integrity number decreased significantly during FFPE sampling. Amplification efficiency also displayed certain variability related with amplicon length and RNA species. We found molecular evidence that short amplicons of mRNA, lncRNA, and circRNA were amplified more efficiently than long amplicons. With the assistance of RefFinder, 5S, SNORD48, miR-103a, and miR-125b were selected as reference genes given their high stability. After normalization, we found that short amplicon markers (e.g., ACTB mRNA and MALAT1 lncRNA) exhibited high consistency of quantification in paired fresh/FFPE samples. In particular, circRNAs (XPO1, HIPK3, and TMEM56) presented relatively consistent and stable expression profiles in FFPE tissues compared with their corresponding linear transcripts. Additionally, we evaluated the influence of prolonged storage time on the amplification of gene transcripts and found that short amplicons still work effectively in archived FFPE biospecimens. In conclusion, our findings demonstrate the possibility of performing accurate quantitative analysis of ncRNAs using short amplicons and standardized RT-qPCR assays in autopsy-derived FFPE samples.

In this study, we elucidate the contribution of repetitive DNA sequences to the establishment of social structures in honeybees (Apis mellifera). Despite recent advancements in understanding the molecular mechanisms underlying the formation of honeybee castes, primarily associated with Notch signaling, the comprehensive identification of specific genomic cis-regulatory sequences remains elusive. Our objective is to characterize the repetitive landscape within the genomes of two honeybee subspecies, namely A. m. mellifera and A. m. ligustica. An observed recent burst of repeats in A. m. mellifera highlights a notable distinction between the two subspecies. After that, we transitioned to identifying differentially expressed DNA elements that may function as cis-regulatory elements. Nevertheless, the expression of these sequences showed minimal disparity in the transcriptome during caste differentiation, a pivotal process in honeybee eusocial organization. Despite this, chromatin segmentation, facilitated by ATAC-seq, ChIP-seq, and RNA-seq data, revealed a distinct chromatin state associated with repeats. Lastly, an analysis of sequence divergence among elements indicates successive changes in repeat states, correlating with their respective time of origin. Collectively, these findings propose a potential role of repeats in acquiring novel regulatory functions.