Search Results (71)

Background/Objectives: Ovarian follicular cysts (OFCs) in dairy cows represent a significant cause of infertility and share striking similarities with polycystic ovary syndrome (PCOS) in women. This study aimed to elucidate the molecular mechanisms underlying OFCs and their relevance to PCOS by profiling differentially expressed (DE) microRNAs (miRNAs) and constructing integrative RNA interaction networks. Methods: Expression analysis of 84 bovine miRNAs was conducted in antral follicular fluid from normal and cystic follicles using miScript PCR arrays. Bioinformatic tools including miRBase, miRNet, and STRING were employed to predict miRNA targets, construct protein–protein interaction networks, and perform gene ontology and KEGG pathway enrichment. Network analyses integrated miRNAs with coding (mRNAs) and non-coding RNAs (circRNAs, lncRNAs, snRNAs). Results: Seventeen miRNAs were significantly dysregulated in OFCs, including bta-miR-18a, bta-miR-30e-5p, and bta-miR-15b-5p, which were associated with follicular arrest, insulin resistance, and impaired steroidogenesis. Upregulated miRNAs such as bta-miR-132 and bta-miR-145 correlated with inflammation, oxidative stress, and intrafollicular androgen excess. Key regulatory lncRNAs such as Nuclear Enriched Abundant Transcript 1 (NEAT1), Potassium Voltage-Gated Channel Subfamily Q Member 1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1), Taurine-Upregulated 1 (TUG1), and X Inactive Specific Transcript (XIST), as well as circRNA/pseudogene hubs, were identified, targeting pathways involved in metabolism, inflammation, steroidogenesis, cell cycle, and apoptosis. Conclusions: The observed transcriptomic changes mirror core features of human PCOS, supporting the use of bovine OFCs as a comparative model. These findings provide novel insights into the regulatory RNA networks driving ovarian dysfunction and suggest potential biomarkers and therapeutic targets for reproductive disorders. This network-based approach enhances our understanding of the complex transcriptomic landscape associated with follicular pathologies in both cattle and women. Full article

HIV-1 infection in microglia induces HIV-associated neurocognitive disorder (HAND). Recent evidence suggests that microglia can be infected with HIV-1 in the active, persistent, or latent replication stages. The molecular mechanisms governing these stages of infection are still the subject of continuous study. In this study, we analyzed the relationship between HIV-1 infection and two lncRNAs, NEAT1 and ZBTB11-AS1, on different days post-infection. We found that on days 1 and 4 post-infection, HIV-1 was actively replicating; meanwhile, by day 21, HIV-1 had entered a persistent stage. We also noted that the expression levels of NEAT1 and ZBTB11-AS1 varied during these different stages of HIV-1 infection in microglia, as did their subcellular localization. We performed an interaction network analysis and identified DDX3X and ZC3HAV1 as hypothetically related to NEAT1 and ZBTB11-AS1 in the C20 human microglial cell line. Additionally, we determined that IL-6, a cytokine regulated by DDX3X and ZC3HAV1, exhibits changes in protein expression levels during both active and persistent HIV-1 infection. Full article

Background: Endometrial receptivity is crucial for successful embryo implantation in assisted reproductive technologies (ARTs). MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have emerged as important post-transcriptional regulators of endometrial function, although their diagnostic and molecular functions are poorly understood. Methods: A systematic review was conducted following PRISMA 2020 principles and registered in PROSPERO (CRD420251001811). We looked at 28 peer-reviewed publications published between 2010 and 2025 that used endometrial tissue, blood, uterine fluid, saliva, and embryo culture medium to study miRNAs and other non-coding RNAs in endometrial receptivity, recurrent implantation failure (RIF), and infertility. Results: MiRNAs like miR-145, miR-30d, miR-223-3p, and miR-125b influence implantation-related pathways such as HOXA10, LIF-STAT3, PI3K-Akt, and Wnt/β-catenin. Dysregulated expression profiles were linked to inadequate decidualization, immunological imbalance, and poor angiogenesis. CeRNA networks that include lncRNAs (e.g., H19 and NEAT1) and circRNAs (e.g., circ_0038383) further regulate miRNA activity. Non-invasive biomarkers derived from plasma, uterine fluid, and embryo media showed high prediction accuracy for implantation outcomes. Conclusions: MiRNA signatures offer a functional and diagnostic blueprint for endometrial receptivity. This systematic review provides a timely and thorough synthesis of the existing literature, with the goal of bridging the gap between molecular discoveries and therapeutic applications. By emphasizing both the mechanistic importance and diagnostic value of certain miRNA signatures, it paves the way for future precision-based techniques in embryo transfer and endometrial assessment in ART. Full article

Long, non-coding RNAs (lncRNAs) are a class of RNAs exceeding 200 nucleotides in length, lacking the ability to be translated into proteins. Over the past few decades, an increasing number of publications have established lncRNAs as potent regulators in a broad spectrum of diseases. They modulate the expression of critical genes by affecting transcription, post-transcription, translation, and protein modification. This regulation frequently involves the interaction of lncRNAs with various molecules, such as proteins, RNA, and DNA. lncRNAs are involved in diseases where stress is a significant factor. In recent years, lncRNAs have been identified as regulators of both innate and adaptive immune responses, playing significant roles in the onset and progression of diseases. Additionally, lncRNAs hold potential as biomarkers or therapeutic targets for numerous stress- and immune-related diseases. lncRNA nuclear-enriched abundant transcript 1 (NEAT1) is a notable example. This review consolidates the latest findings about the role of lncRNA NEAT1 in stress response and immune cell function in non-cancer diseases. It summarizes studies on NEAT1 regulating stress response, both innate and adaptive immunity, and its potential as a biomarker and therapeutic target for stress- and immune-related diseases. Full article

The psoas major muscle (PMM) is a piece of pork with good tenderness and high value. Intramuscular fat (IMF) content, serving as a pivotal indicator of pork quality, varies greatly among pigs within the same breed. However, there is a paucity of studies focusing on investigating the molecular mechanism of PMM IMF deposition in the same pig breed. The present study aimed to identify the potential genes related to the IMF content of PMM in low- and high-IMF Saba pigs based on transcriptome data analysis. The data used in this study were the RNA sequences of PMM from 12 Saba pigs (PRJNA1223630, from our laboratory) and gene expression profiles (GSE207279) acquired from the NCBI Sequence Read Archive database and the GEO database, respectively, together with data on the fatty acid and amino acid composition of the 12 Saba pigs’ PMM. It was found that the high-IMF pigs exhibited significantly elevated levels of saturated fatty acids and (mono)unsaturated fatty acids, especially C14:0, C16:0, C20:0, C16:1, C18:1n9c, and C20:2, compared with those in the low-IMF pigs (p < 0.05 or p < 0.01). A total of 370 differentially expressed genes (DEGs) (221 up- and 149 down-regulated) were identified based on PRJNA1223630. Then, 20 hub genes were identified through protein–protein interaction (PPI) network analysis. Four potential fat-deposition-related genes (DGAT2, PCK1, MELK, and FASN) were further screened via the intersection of the candidate genes identified by the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the top five genes ranked by the Random Forest (RF) method based on the 20 hub genes and were validated in the test gene set (GSE207279). The constructed mRNA (gene)–miRNA–lncRNA network, involving miRNAs (miR-103a-3p, miR-107, and miR-485-5p), lncRNAs (XIST, NEAT1, and KCNQ1OT1), and FASN, might be crucial for IMF deposition in pigs. These findings might delineate valuable regulatory molecular mechanisms coordinating IMF deposition and could serve as a beneficial foundation for the genetic improvement of pork quality. Full article

Long noncoding RNAs (lncRNAs) are RNA molecules exceeding 200 nucleotides that do not encode proteins yet play critical roles in regulating gene expression at multiple levels, such as chromatin modification and transcription. These molecules are significantly engaged in cancer progression, development, metastasis, and chemoresistance. However, the function of lncRNAs in epithelial ovarian cancer (EOC) has not yet been thoroughly studied. EOC remains challenging due to its complex molecular pathogenesis, characterized by genetic and epigenetic alterations. Emerging evidence suggests that lncRNAs, such as XIST, H19, NEAT1, and MALAT1, are involved in EOC by modulating gene expression and signaling pathways, influencing processes like cell proliferation, invasion, migration, and chemoresistance. Despite extensive research, the precise mechanism of acting of lncRNAs in EOC pathogenesis and treatment resistance still needs to be fully understood, highlighting the need for further studies. This review aims to provide an updated overview of the current understanding of lncRNAs in EOC, emphasizing their potential as biomarkers and therapeutic targets. We point out the gaps in the knowledge regarding lncRNAs’ influence on epithelial ovarian cancer (EOC), deliberating on new possible research areas. Full article

Diabetic cardiomyopathy (DCM), a critical complication of type 2 diabetes mellitus (T2DM), is marked by metabolic dysfunction, oxidative stress, and chronic inflammation, ultimately progressing to heart failure. This study investigated the synergistic therapeutic potential of Hippophae rhamnoides L. (sea buckthorn, SBU) extract and metformin in a mouse model of T2DM-induced DCM. T2DM was induced using a 45% high-fat-AGEs-enriched diet, followed by treatment with SBU, metformin, or their combination. Treatment effects were monitored through bioinformatic analysis, chemoinformatic prediction, behavioral testing, biochemical assays, histopathological evaluations and gene expression profiles. Based on bioinformatic analysis, we identified key hub genes involved in the diabetic cardiomyopathy including SERPINE1, NRG1, MYH11, PTH, NR4A2, NRF2, PGC1α, GPX4, ATF1, ASCL2, NOX1, NLRP3, CCK8, COX2, CCL2, PTGS2, EGFR, and oncostatin, which are pivotal in modulating the ferroptosis pathway. Furthermore, the expression of long non-coding RNAs (lncRNAs) NEAT1 and MALAT1, critical regulators of inflammation and cell death, was effectively downregulated, correlating with decreased levels of the pro-inflammatory marker oncostatin. The combined therapy significantly improved glucose regulation, reduced systemic inflammation and protected the heart from oxidative damage. Histopathological analysis revealed notable reductions in cardiac necrosis and fibrosis. Particularly, the combination therapy of SBU and metformin demonstrated a synergistic effect, surpassing the benefits of individual treatments in preventing cardiac damage. These findings highlight the potential of integrating SBU with metformin as a novel therapeutic strategy for managing DCM by targeting both metabolic and ferroptosis-related pathways. This dual intervention opens promising avenues for future clinical applications in diabetic heart disease management, offering a comprehensive approach to mitigating the progression of DCM. Full article

Background: The majority of head and neck cancers (HNCs) occur in the larynx. In clinical practice, adverse effects are frequently observed in laryngeal cancer (LC) patients undergoing radiotherapy (RT). Therefore, investigating markers that can predict these unfavorable events is of interest. Long non-coding RNAs (lncRNAs) have emerged as potential biomarkers for the early identification of patients susceptible to post-RT toxicity. MALAT1 and NEAT1 regulate various cellular processes, the inflammatory response, and resistance to anti-cancer treatments; however, their impact on the portability of post-RT adverse effects remains unknown. The aim of this study was to evaluate the clinical value of two plasma-circulating lncRNAs, MALAT1 and NEAT1, as predictive biomarkers for post-RT adverse effects in LC patients. Methods: The expression levels of the studied lncRNAs were determined using real-time quantitative reverse transcription PCR (qRT-PCR) in plasma samples obtained from 70 LC patients before the initiation of RT. These levels were then correlated with patient outcomes. Results: A low expression of MALAT1 was associated with a significantly higher probability of anemia, liver failure, and severe malnutrition (OR = 5.36; p = 0.040, OR = 6.07; p = 0.037, OR = 9.75; p < 0.001, respectively) after the completion of RT. Similarly, patients with low NEAT1 expression had a significantly higher risk of anemia, liver failure, and mild or severe malnutrition (OR = 5.26; p = 0.020, OR = 5.70; p = 0.016, OR = 13.09; p = 0.002, respectively). Simultaneous lower expression levels of both lncRNAs were significantly associated with shorter median overall survival (OS) in RT-treated LC patients (HR = 5.44; p = 0.001). Conclusions: The analysis of MALAT1 and NEAT1 expression indicates clinical utility in predicting toxic events induced by RT-based therapy. Full article

The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd tissue samples surgically removed from patients with primary hyperparathyroidism (PHPT) were collected and profiled for gene, microRNA, and lncRNA expression (n = 27). Based on a gene set including MEN1, CDC73, GCM2, CASR, VDR, CCND1, and CDKN1B, the transcriptomic profiles were analyzed using a cluster analysis. The expression levels of CDC73 and CDKN1B were the main drivers for clusterization. The samples were separated into two main clusters, C1 and C2, with the latter including two subgroups of five PAds (C2A) and nineteen PAds (C2B), both differing from C1 in terms of their lower expression of CDC73 and CDKN1B. The C2A PAd profile was also associated with the loss of TP73, an increased expression of HAR1B, HOXA-AS2, and HOXA-AS3 lncRNAs, and a trend towards more severe PHPT compared to C1 and C2B PAds. C2B PAds were characterized by a general downregulated gene expression. Moreover, CCND1 levels were also reduced as well as the expression of the lncRNAs NEAT1 and VLDLR-AS1. Of note, the deregulated lncRNAs are predicted to interact with the histones H3K4 and H3K27. Patients harboring C2B PAds had lower ionized and total serum calcium levels, lower PTH levels, and smaller tumor sizes than patients harboring C2A PAds. In conclusion, PAds display heterogeneous transcriptomic profiles which may contribute to the modulation of clinical and biochemical features. The general downregulated gene expression, characterizing a subgroup of PAds, suggests the tumor cells behave as quiescent resting cells, while the severity of PHPT may be associated with the loss of p73 and the lncRNA-mediated deregulation of histones. Full article

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. Full article

Chronic obstructive pulmonary disease (COPD) and lung cancer represent formidable challenges in global health, characterized by intricate pathophysiological mechanisms and multifaceted disease progression. This comprehensive review integrates insights from diverse perspectives to elucidate the intricate roles of long non-coding RNAs (lncRNAs) in the pathogenesis of COPD and lung cancer, focusing on their diagnostic, prognostic, and therapeutic implications. In the context of COPD, dysregulated lncRNAs, such as NEAT1, TUG1, MALAT1, HOTAIR, and GAS5, emerge as pivotal regulators of genes involved in the disease pathogenesis and progression. Their identification, profiling, and correlation with the disease severity present promising avenues for prognostic and diagnostic applications, thereby shaping personalized disease interventions. These lncRNAs are also implicated in lung cancer, underscoring their multifaceted roles and therapeutic potential across both diseases. In the domain of lung cancer, lncRNAs play intricate modulatory roles in disease progression, offering avenues for innovative therapeutic approaches and prognostic indicators. LncRNA-mediated immune responses have been shown to drive lung cancer progression by modulating the tumor microenvironment, influencing immune cell infiltration, and altering cytokine production. Their dysregulation significantly contributes to tumor growth, metastasis, and chemo-resistance, thereby emphasizing their significance as therapeutic targets and prognostic markers. This review summarizes the transformative potential of lncRNA-based diagnostics and therapeutics for COPD and lung cancer, offering valuable insights into future research directions for clinical translation and therapeutic development. Full article

Breast cancer is a leading cause of cancer-related deaths among women both worldwide and in Poland. Consequently, ensuring equitable access to diagnostic tests for all populations is crucial, alongside the urgent need to develop new, minimally invasive methods for early cancer detection with a particular focus on metastasis. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of cancer metastasis. This review aims to investigate the potential of lncRNAs as novel biomarkers for breast cancer, focusing on their mechanisms, clinical relevance, and therapeutic implications. A comprehensive literature search was conducted using PubMed and Google Scholar databases, targeting publications from 2013 to 2024. Keywords included “lncRNA”, “biomarker”, “breast cancer”, “metastasis”, “prognosis”, and “diagnosis”. A total of 111 articles were selected based on their relevance and quality. Recent studies have identified numerous lncRNAs such as HOTAIR, MALAT1, BANCR, NEAT1, H19, and GAS5 as key regulators of various metastatic processes in breast cancer. They can be both upregulated and downregulated. Clinical studies have shown that abnormal lncRNA expression correlates with poor prognosis, higher metastatic potential, and therapy resistance in breast cancer patients. LncRNAs have significant potential as novel biomarkers for breast cancer metastasis because of their regulatory roles in metastasis-related processes and detectability in body fluids. Further research is essential to validate these findings in larger clinical studies and to develop lncRNA-based diagnostic and therapeutic tools, ultimately improving patient outcomes in breast cancer. Full article

Glioblastoma (GBM), as the most common primary brain tumor, usually results in an extremely poor prognosis, in which glioma stem cells (GSCs) and their immunosuppressive microenvironment prominently intervene in the resistance to radiotherapy and chemotherapy that directly leads to tumor recurrence and shortened survival time. The specific mechanism through which exosomes generated from GSCs support the creation of an immunosuppressive microenvironment remains unknown, while it is acknowledged to be engaged in intercellular communication and the regulation of the glioma immunosuppressive microenvironment. The elevated expression of LncRNA-NEAT1 was found in glioma cells after radiotherapy, chemotherapy, and DNA damage stimulation, and NEAT1 could promote the malignant biological activities of GSCs. Emerging evidence suggests that lncRNAs may reply to external stimuli or DNA damage by playing a role in modulating different aspects of tumor biology. Our study demonstrated a promotive role of the carried NEAT1 by GSC-derived exosomes in the polarization of M2-like macrophages. Further experiments demonstrated the mediative role of miR-125a and its target gene STAT3 in NEAT1-induced polarization of M2-like macrophages that promote glioma progression. Our findings elucidate the mechanism by which GSCs influence the polarization of M2-like macrophages through exosomes, which may contribute to the formation of immunosuppressive microenvironments. Taken together, our study reveals the miR-125a-STAT3 pathway through which exosomal NEAT1 from treatment-resistant GSCs contributes to M2-like macrophage polarization, indicating the potential of exosomal NEAT1 for treating glioma. Full article

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14–16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients’ blood. Full article

Paraspeckles are nuclear condensates formed by NEAT1_2 lncRNA and different RNA-binding proteins. In general, these membraneless organelles function in the regulation of gene expression and translation and in miRNA processing, and in doing this, they regulate cellular homeostasis and mediate pro-survival in the cell. Despite evidence showing the importance of paraspeckles in the stress response, the dynamics of paraspeckles and their components under conditions of osmotic stress remain unknown. We exposed HEK293T cells to sorbitol and examined NEAT1_2 expression using real-time PCR. Localization and quantification of the main paraspeckle components, NEAT1_2, PSPC1, NONO, and SFPQ, in different cellular compartments was performed using smFISH and immunofluorescence. Our findings showed a significant decrease in total NEAT1_2 expression in cells after osmotic stress. Sorbitol shifted the subcellular localization of NEAT1_2, PSPC1, NONO, and SFPQ from the nucleus to the cytoplasm and decreased the number and size of NEAT1_2 foci in the nucleus. PSPC1 formed immunoreactive cytoplasmic fibrils under conditions of osmotic stress, which slowly disassembled under recovery. Our study deepens the paraspeckle dynamics in response to stress, suggesting a novel role for NEAT1_2 in the cytoplasm in osmotic stress and physiological conditions. Full article