MicroRNAs (miRNAs) are small non-coding RNAs that act as critical regulators of gene expression by repressing mRNA translation. The role of miRNAs in cell physiology spans from cell cycle control to cell proliferation and differentiation, both during development and in adult tissues. Accordingly, dysregulated expression of miRNAs has been reported in several diseases, including cancer, where miRNAs can act as oncogenes or oncosuppressors. Of note, miRNA signatures are also under investigation for classification, diagnosis, and prognosis of cancer patients. Brain tumours are primarily associated with poor prognosis and high mortality, highlighting an urgent need for novel diagnostic, prognostic, and therapeutic tools. Among miRNAs investigated in brain tumours, miR-326 has been shown to act as a tumour suppressor in adult and paediatric brain cancers. In this review, we describe the role of miR-326 in malignant as well as benign cancers originating from brain tissue. In addition, since miR-326 expression can be regulated by other non-coding RNA species, adding a further layer of regulation in the cancer-promoting axis, we discuss this miRNA's role in targeted therapy for brain cancers.

This study found that in patients with SLE (n = 5), lethal (let)-7f-5p expression was significantly downregulated in peripheral blood mononuclear cells. Further, high-throughput RNA sequencing was used to mine the differential transcriptome expression in renal tissue exosomes of systemic lupus erythematosus (SLE)-prone mice, and bioinformatics was utilized to analyze non-coding RNAs and coding RNAs in exosomes for their possible roles in SLE. In renal tissues of MRL/lpr SLE-prone mice with exosomes and Pristane-induced SLE mice, we also demonstrated aberrant expression levels of microRNA (miRNA) let-7f-5p. Meanwhile, in the macrophage inflammation model, the expression levels of let-7f-5p were downregulated, that of guanylate binding protein (Gbp2 and Gbp7) were upregulated, and the inflammatory state of macrophages was alleviated following transfection with the let-7f-5p mimic. Co-culturing mesenchymal stem cells with a macrophage model of inflammation resulted in increased let-7f-5p expression and downregulated inflammatory factors, Gbp2 and Gbp7 expression in macrophages. Dual luciferase reporter gene assays confirmed that let-7f-5p directly binds to the 3' UTR of Gbp7 to regulate its expression. Let-7f-5p regulation of the Gbp family is involved in SLE pathogenesis and is a biomarker associated with the inflammatory response with potential clinical applications.

Cancer metastasis is the dissemination of tumor cells from the primary tumor site to other parts of the body via the lymph system or bloodstream. Metastasis is the leading cause of cancer associated death. Despite the significant advances in cancer research and treatment over the past decades, metastasis is not fully understood and difficult to predict in advance. In particular, distant metastasis is more difficult to predict than lymph node metastasis, which is the spread of cancer cells to nearby lymph nodes. Distant metastatic sites is even more difficult to predict than the occurrence of distant metastasis because the problem of predicting distant metastatic sites is a multi-class and multi-label classification problem; there are more than two classes for distant metastatic sites (bone, liver, lung, and other organs), and a single sample can have multiple labels for multiple metastatic sites. This paper presents a new method for predicting distant metastatic sites based on correlation changes of miRNAs with competing endogenous RNAs (ceRNAs) in individual cancer patients. Testing the method on independent datasets of several cancer types demonstrated a high prediction performance. In comparison of our method with other state of the art methods, our method showed a much better and more stable performance than the others. Our method can be used as useful aids in determining treatment options by predicting if and where metastasis will occur in cancer patients at early stages.

Despite the high morbidity of thyroid cancer (THCA), the underlying molecular pathology remains elusive. That autism-associated protein POGZ has recently been involved in tumorigenesis intrigues us exploring its relevant molecular regulatory network in THCA. Clinical characteristics and intermolecular relationships were dissected by bioinformatics. Interaction between POGZ and MAD2L2 was examined by Co-IP assay. Targeting relationships between miR-27b-3p and POGZ/LINC01355 was verified by sequence prediction and dual-luciferase reporter detection. Cellular effects of genes were assessed by CCK-8 assay, clone formation assay, and Transwell assay, and further confirmed by a tumor-bearing nude mice model. Our results demonstrated a decrease in POGZ expression in THCA tissues and cell lines, and an interaction between POGZ and MAD2L2 protein. POGZ inhibited both the proliferation and motility of THCA cells, with these effects being reversed upon MAD2L2 silencing. LINC01355 exhibited low expression level and a positive correlation with POGZ in THCA. Both miR-27b-3p and LINC01355 were identified as regulators of POGZ through targeting. Elevated miR-27b-3p suppressed POGZ expression. LINC01355 promoted POGZ and counteracted the inhibitory effects of miR-27b-3p. Furthermore, miR-27b-3p increased the proliferation and motility of THCA cells, an effect that was blocked by LINC01355. At the animal level, POGZ, LINC01355, and MAD2L2 all attenuated tumor growth in THCA. Collectively, POGZ restrains THCA growth by interacting with MAD2L2 protein, and POGZ modulation involves a complex interplay orchestrated by LINC01355-targeted miR-27b-3p. By reporting the first POGZ-focused ceRNA network involving noncoding RNA in THCA, our study paves the way for exploring POGZ-related pathways and developing new therapeutic strategies in cancer.

The online version contains supplementary material available at 10.1007/s13205-025-04231-7.

Alzheimer's disease is a progressive neurodegenerative condition that is the most frequent reason for dementia. Due to the increasing trend of aging in societies, it will place a large social and financial burden on society. Although beta amyloid plaques and the formation of neurofibrillary tangles are mentioned as the main events in this disorder, the exact molecular pathology and inflammatory regulatory networks involved in neuroinflammatory events, as a fundamental pathogenic mechanism remain unknown. Understanding these molecular network pathways in addition to helping to understand the pathogenesis of Alzheimer's disease, can also help in the early diagnosis as well as the control of inflammatory processes that are involved in its progression. So, in this study, we intend to have an overview on the regulatory lncRNAs of Alzheimer's disease and their related miRNA and mRNAs, as well as the relationship of these regulatory pathways with inflammatory processes, so that we can provide a perspective for future studies in the field of diagnosis and possibly treatment of this disorder.

Dioscin is a natural, bioactive steroid saponin that has the antiarthritic activity. Circular RNAs (circRNAs) are stable noncoding RNAs involving in the pathogenesis of rheumatoid arthritis (RA). Here, this study aimed to probe the role and mechanism of dioscin and circ_0008267 in RA progression. Cell proliferation, apoptosis, invasive, and migratory abilities, as well as inflammatory response were evaluated by CCK-8 assay, EdU assay, flow cytometery, transwell assay, wound healing assay, and ELISA analysis, respectively. Levels of genes and protein were tested by qRT-PCR and western blotting. The interaction between miR-942-5p and circ_0008267 or FK506-binding protein 5 (FKBP5) was confirmed using dual-luciferase reporter and RNA pull-down assays. Dioscin treatment was demonstrated to suppress RA-FLS proliferation, invasion, migration, and inflammatory response, but induced cell apoptosis. Circ_0008267 is a stable circRNA, and was increased in RA samples. Moreover, its expression was reduced by dioscin in RA-FLS, overexpression of circ_0008267 reversed the effects of dioscin on RA-FLS. Mechanistically, circ_0008267 acted as a sponge for miR-942-5p, which targeted FKBP5. Dioscin reduced FKBP5 expression, but elevated miR-942-5p level in RA-FLS. MiR-942-5p inhibition or FKBP5 upregulation abolished the inhibitory effects of dioscin on RA-FLS dysfunction. Moreover, circ_0008267 deficiency impaired RA-FLS proliferation, invasion, migration, and inflammation through regulating FKBP5. Dioscin suppressed the proliferation, invasion, migration, and inflammatory response in RA-FLS via circ_0008267/miR-942-5p/FKBP5 axis, providing new insights for RA prevention.

Chronic trauma is a prevalent and significant complication of diabetes. Mesenchymal stem cell(MSC)-derived exosomes (Exos) have been reported to accelerate the healing of chronic diabetic wounds. MSCs pretreated with chemical or biological factors were reported to enhance the biological activity of MSC-derived exosomes. Hence, this study investigated the role of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) pretreated with metformin (MET) on diabetic wound healing. The results showed that MET-Exos promoted endothelial cell migration, tube formation, and angiogenesis, leading to accelerated wound healing in diabetic mice. Mechanistically, MET-Exos upregulated LINC-PINT, which, through competitive binding to miR-139-3p, activated FOXC2, a key regulator of angiogenesis. These data reveal that MET-Exos might promote revascularization and wound healing through the LINC-PINT/miR-139-3p/FOXC2 axis, showing its potential as a therapeutic modality for diabetic wounds.

MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression. Among these, miR-660, located on chromosome Xp11.23, is increasingly studied for its role in cancer due to its abnormal expression in various biological contexts. It is regulated by 8 competing endogenous RNAs (ceRNAs), which adds complexity to its function. miR- 660 targets 19 genes involved in 6 pathways such as PI3K/AKT/mTOR, STAT3, Wnt/β-catenin, p53, NF‑κB, and RAS, influencing cell cycle, proliferation, apoptosis, and invasion/migration. It also plays a role in resistance to chemotherapies like cisplatin, gemcitabine, and sorafenib in lung adenocarcinoma (LUAD), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC), thus highlighting its clinical importance. Additionally, leveraging liposomes as nanocarriers presents a promising avenue for enhancing cancer drug delivery. Our comprehensive study not only elucidates the aberrant expression patterns, biological functions, and regulatory networks of miR-660 and its ceRNAs but also delves into the intricate signaling pathways implicated. We envisage that our findings will furnish a robust framework and serve as a seminal reference for future investigations of miR-660, fostering advancements in cancer research and potentially catalyzing breakthroughs in cancer diagnosis and treatment paradigms.

Breast cancer, a highly prevalent form of cancer worldwide, has observed a steady increase in its prevalence over the past few decades. This rise can be attributed to the complex nature of the disease, characterized by its heterogeneity, ability to metastasize, and resistance to various treatment. In the field of cancer research, long non-coding RNAs (lncRNAs) are of special interest, which play an important role in the development and progression of various tumors, including breast cancer. LncRNAs affect the tumor microenvironment by attracting diverse immunosuppressive factors and controlling the differentiation of immune cells, often referred to as myeloid and lymphoid cells, which contributes to immune escape of tumor cells. Among the lncRNA families, the small nucleolar RNA host gene (SNHG) family has been found to be dysregulated in breast cancer. These SNHGs have been implicated in crucial cellular processes such as cell proliferation, invasion, migration, resistance to therapies, apoptosis, as well as immune cell regulation and differentiation. Consequently, they have great potential as diagnostic and prognostic biomarkers as well as potential therapeutic targets for breast cancer. In this comprehensive review, we aim to summarize the recent advances in the study of SNHGs in breast cancer pathogenesis and their role in regulating the activity of immune cells in the tumor microenvironment through affecting SNHGs/miRNA/mRNA pathways, with the aim of providing new insights into the treatment of breast cancer.

Long non-coding RNAs (lncRNAs) act as molecular sponges for microRNAs (miRNAs) and indirectly regulate gene expression. Currently, sequence-based prediction methods for lncRNA-miRNA interactions primarily rely on extracting features from full-length sequences, which suffers from the disadvantage of information redundancy.

In this study, we proposed a machine learning method called BSILMI, which predicts lncRNA-miRNA interactions based on sequence and structural information of potential binding site. BSILMI employs XGBoost and focuses on information from potential binding sites between lncRNAs and miRNAs, including the binding free energy, binding site scores, and unpaired probability of RNA folding. BSILMI outperformed LncMirNet, which is a state-of-the-art method. Additionally, we presented a new framework for negative sampling, in which potential interaction pairs are eliminated through sequence similarity alignment. This improves the reliability of the negative sample set. Finally, the key factors influencing the predictions were analyzed using SHAP feature importance analysis.

Our results demonstrated that binding site information plays a crucial role in predicting lncRNA and miRNA interactions. This provides new insights into the research of RNA interactions.

Although triptolide has demonstrated efficacy in treating oral squamous cell carcinoma (OSCC), its precise molecular mechanism remains unclear. This study investigated the mechanism underlying triptolide's action in lncRNA-mediated competing endogenous RNA (ceRNA) regulation.

The impact of triptolide on OSCC in vivo was validated using a xenograft tumor model. Whole-transcriptome sequencing and bioinformatics analysis were conducted to construct the lncRNA-miRNA-mRNA regulatory network. Relative gene and protein expression levels were confirmed using qRT-PCR and Western blot. Dual-luciferase assays were performed to assess target interactions, while cell proliferation was measured using CCK8 assays, and cell migration and invasion were evaluated via wound healing and transwell assays.

Triptolide markedly reduced proliferation, migration, and invasion in Cal27 and Tca8113 cells. After 22 days of triptolide treatment, the tumor volume of mice gradually shrank. This led to significant upregulation of cleaved Caspase-3 and Bax, alongside downregulation of Bcl-2. Transcriptome sequencing and bioinformatics analysis identified 266 differentially expressed mRNAs, 528 lncRNAs, and 85 miRNAs. Enhanced expression of lncRNA MSTRG.24214.1 and mRNA LCN2, along with reduced expression of miR-939-5p, was observed in the triptolide group.

The lncRNA-miRNA-mRNA ceRNA network associated with triptolide's impact on OSCC was successfully established. Triptolide suppressed OSCC development and progression both in vitro and in vivo, potentially through modulation of the MSTRG.24214.1-miR-939-5p-LCN2 axis. These findings offer a solid foundation for future personalized triptolide-based therapeutic approaches.

Breast cancer is a leading malignancy in women, with mortality disparities between developed and underdeveloped regions. Accumulating evidence suggests that the competitive endogenous RNA (ceRNA) regulatory networks play paramount roles in various human cancers. However, the complexity and behavior characteristics of the ceRNA network in breast cancer progression have not been fully elucidated. The expression profiles of three RNAs (long non-coding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) were extracted from breast cancer and adjacent samples were sourced from the TCGA database. The SLC26A4-AS1- hsa-miR-19a-3p-NTRK2 ceRNA network related to the prognosis of breast cancer was obtained by performing bioinformatics analysis. Importantly, we identified the SLC26A4-AS1/NTRK2 axis within the ceRNA network through correlation analysis and found it to be a potential prognostic model in clinical outcomes based on Cox regression analysis. Moreover, methylation analysis suggests that the aberrant downregulation of the SLC26A4-AS1/NTRK2 axis might be attributed to hypermethylation at specific sites. Immune infiltration analysis indicates that the SLC26A4-AS1/NTRK2 axis may have implications for the alteration of the tumor immune microenvironment and the emergence and progression of immune evasion in breast cancer. Finally, we validated the expression of SLC26A4-AS1-hsa-miR-19a-3p-NTRK2 in breast cancer cell lines. In summary, the present study posits that the SLC26A4-AS1/NTRK2 axis, based on the ceRNA network, could be a novel and significant prognostic factor associated with breast cancer diagnosis and outcomes.

Recently, long non-coding RNAs have gained an increasing amount of attention in treating lung cancer. However, a full understanding of how CCAT1 lncRNA works against proliferation is not yet available. Therefore, we assess the impact of CCAT1 on the lung cancer cell proliferation, apoptosis, and doxorubicin (DOX) sensitivity, and the involvement of miR-181a/CPEB2 pathway. For this purpose, lung cancer A549 cells were exposed to siRNA against CCAT1 and DOX and cell viability were measured by MTT assay. ELISA was used to evaluate cell apoptosis. The protein and mRNA expression levels of apoptotic markers, miR-181a and CPEB2 were measured by western blot and qRT-PCR. Knock-downing CCAT1 inhibited the cell viability of A549 cells. In addition, si-CCAT1 treatment increased apoptosis in both cell lines via modulating the anti- and pro-apoptotic markers. Si-CCAT1 increased the levels miR-181a and decreased CPEB2 in A549 cells. In conclusion, our study has provided strong evidence that lncRNA CCAT1 decreased the sensitivity to doxorubicin in lung cancer cells by regulating the miR-181a/CPEB2 axis.

Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer known for its toxic effects on the male reproductive system. Green tea polyphenols (GTPs), recognized for their antioxidant and anti-inflammatory properties, have demonstrated protective effects on various organs, but the mechanisms by which GTPs mitigate DEHP-induced testicular damage remain unclear. Healthy male C57BL/6J mice were divided into five groups: control, DEHP, DEHP + GTP treatment, GTP, and oil groups. Testicular histopathological changes were assessed using hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), and Masson staining. Ultrastructural alterations were examined through transmission electron microscopy. High-throughput sequencing was performed to analyze the expression of mRNA, miRNA, and lncRNA and construct an lncRNA-miRNA-mRNA regulatory network for identifying key regulatory axes. Mice in the DEHP group exhibited significant testicular damage, including reduced sperm count, mitochondrial deformation, and endoplasmic reticulum dilation. GTP treatment notably improved testicular structural integrity, restored sperm count, and alleviated mitochondrial and endoplasmic reticulum damage. Additionally, DEHP significantly increased activated CD8+ T cells, which were reduced with GTP treatment. High-throughput sequencing revealed that GTP treatment exerted protective effects through the regulation of six key lncRNA-miRNA-mRNA axes. GTPs significantly protect against DEHP-induced testicular damage, and the lncRNA-miRNA-mRNA regulatory axes play a potential role in this process.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory condition characterized by progressive airflow limitation, which may be caused by genetic and environmental factors. Furthermore, epigenetic mechanisms could provide valuable insights into the complex interactions between environment and genes and subsequent development of the disease. The aim of this study is to provide a systematic review of the latest knowledge on epigenetic modifications that characterize COPD, summarizing epigenetic factors that could serve as potential novel biomarkers and therapeutic targets for the treatment of COPD patients. We queried the PubMed and Scopus electronic databases with specific keywords, in May 2024, according to the PRISMA guidelines, and articles were included if they met all the inclusion criteria and survived a quality assessment. We identified 5414 publications in our systematic search. Among them, only 51 articles met the criteria of COPD-associated epigenetic modifications in human patients compared to the control group. Eight studies described DNA methylation, one study histone modifications, and forty-two studies non-coding RNAs. Apoptosis and inflammatory pathways have been found to be the main mechanisms regulated by epigenetic elements in COPD patients. In addition, non-coding RNAs may be useful as biomarkers or therapeutic targets of pulmonary disease. Future studies will be needed to confirm the role of epigenetic elements associated with COPD.

Multi-drug resistance-associated protein 1 (MRP1) plays critical roles in the multi-drug resistance (MDR) of cancer cells, LncRNA HOTAIR is closely related to MDR in lung cancer, however, the effects of HOTAIR on MRP1 expression and MDR in lung cancer cells (A549/DDP) remain unknown. In this study, the effects of HOTAIR on MRP1 gene expression and MDR in A549/DDP cells were monitored. LncRNA HOTAIR was upregulated in A549/DDP cells, and overexpression of HOTAIR promoted MRP1 expression and MDR development. The opposite trend was observed when HOTAIR was silenced in A549/DDP cells. To uncover the role of LncRNA HOTAIR in the MDR of human lung cancer, the effects of Egr1 on MRP1 gene expression and MDR in A549/DDP cells were monitored. The results showed that Egr1 could bind to the MRP1 promoter at site -53/-42 bp and regulate MRP1 expression. Egr1 knock-down reduced MRP1 expression, while Egr1 overexpression increased it. Further, the results demonstrated that LncRNA HOTAIR mediated the effects of Egr1 on MRP1 and MDR via sponging of miR-6807-3p. Moreover, miR-6807-3p exerts its function by targeting the Egr1 3'UTR. In conclusion, the results revealed the novel HOTAIR/miR-6807-3p/Egr1 axis in the regulation of MRP1 expression and MDR in lung cancer cells.

The global issue of salinization has made the use of saline-alkaline water in aquaculture increasingly vital. CircRNAs are a new type of endogenous non-coding RNA. Under high saline-alkaline stress, how circRNAs regulate the stress response of Litopenaeus vannamei, especially the mechanism of its immune and metabolic functions, is still unclear. This study aimed to analyze the expression profile of circRNAs and explore their response mechanisms in L. vannamei under the combined influence of high alkalinity and high pH. The results indicated that 127, 157, and 146 differentially expressed circRNAs (DECs) and 1401, 1547, and 1540 differentially expressed mRNAs (DEGs) were identified in the high-pH, alkalinity, and interaction groups, respectively. KEGG enrichment analysis revealed that DECs were mainly enriched in pathways such as sulfur metabolism, glycerophospholipids, and oxidative phosphorylation. The activities of antioxidant-related enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH - PX), increased, while the activities of energy - metabolism-related enzymes, like hexokinase (HK) and pyruvate kinase (PK), decreased. By combining weighted gene-related network analysis (WGCNA) with circRNA - mRNA data, it was found that the expression levels of essential genes related to metabolisms, such as novel_circ_007011, novel_circ_004981, and novel_circ_021024, declined. Gene-silencing experiments demonstrated that novel_circ_004981 and novel_circ_021024 could regulate the expression of glutathione peroxidase (GPx) and carbonic anhydrase - 3 (cah - 3) and further regulate the metabolic pathway and antioxidant system of L. vannamei. This study provides theoretical support for further understanding the stress-response mechanisms of circRNAs in L. vannamei under high-pH and alkalinity stress and offers a scientific basis for the development of saline-alkali aquaculture.

The tumor microenvironment (TME) plays a crucial role in the development and progression of gastric cancer (GC). The TME comprises a network of cancer cells, immune cells, fibroblasts, endothelial cells, and extracellular matrix components, which provide a supportive niche for cancer cells. This study investigates the role of TME-derived exosomal competitive endogenous RNAs (ceRNAs), particularly long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as major regulating agents in GC development. Exosomal ceRNAs control gene expression across several TME components, amplifying cancer hallmarks like cell proliferation, invasion, metastases, and chemoresistance. They promote dynamic interplay between cancer cells and adjacent stromal cells, enabling tumor development through immune suppression, angiogenesis, and epithelial-mesenchymal transition (EMT). Exosomal ceRNAs can modify the TME, creating a pro-tumorigenic milieu and preparing cancer cells to avoid immunological responses, defy death, and adapt to therapeutic pressures. This review highlights the understudied interactions between the TME and exosomal ceRNAs in gastric cancer and emphasizes their potential utility as diagnostic and therapeutic tools.

Fatty liver hemorrhage syndrome (FLHS) is the most common metabolic diseases in laying hens during the late-laying period, and it causes a significant economic burden on the poultry industry. The competing endogenous RNA plays crucial roles in the occurrence and development of fatty liver. Based on the previously constructed lncRNA-miRNA-mRNA networks, we selected the axis of ENSGALT00000079786-LPL-miR-143-5p for further study to elucidate its mechanistic role in development of fatty liver. In this study, we identified a novel highly conserved lncRNA (ENSGALT00000079786) in poultry, which we designated as lncRNA A2ml2 based on its chromosomal location. Fluorescent in situ hybridization (FISH) revealed that lncRNA A2ml2 was localized in both the nucleus and cytoplasm. Dual-luciferase reporter assay validated the targeted relationship between lncRNA A2ml2, miR-143-5p, and the LPL gene. To further analyze the lncRNA A2ml2 and miR-143-5p function, lncRNA A2ml2 overexpression vector was successfully constructed and transfected into Leghorn male hepatocellular (LMH) cells, which could remarkably inhibit cellular lipid deposition was detected by oil red staining (P < 0.01), the opposite occurred for miR-143-5p (P < 0.01). qPCR demonstrated an inverse correlation between miR-143-5p expression and lncRNA A2ml2 expression, and confirmed that miR-143-5p directly target lncRNA A2ml2. Similarly, we found an inverse correlation between expression of LPL and the expression of miR-143-5p. To further investigate the interactions among these three factors and their effects on cellular lipid metabolism, we assessed the expression levels of LPL by co-transfecting lncRNA A2ml2 with miR-143-5p mimic and miR-143-5p mimic binding site mutants. Co-transfection experiments showed that miR-143-5p diminished the promoting effect of lncRNA A2ml2 on LPL. Meanwhile, miR-143-5p has the capacity to mitigate the suppressive impact of lncRNA A2ml2 overexpression on lipid accumulation in LMH cells. The results revealed that lncRNA A2ml2 attenuated hepatic lipid accumulation through negatively regulating miR-143-5p and enhancing LPL expression in LMH cells. Our findings offer novel insights into ceRNA-mediated in FLHS and identify a novel lncRNA as a potential molecular biomarker.

Alkylating cellular DNA, sulfur mustard (SM) is a chemical warfare agent that causes severe damage to the skin, eyes, and respiratory tract. Exposure can result in painful burns, chronic lung disease, immune system suppression, and an increased chance of developing cancer. The symptoms of itching, redness, and blistering are frequently followed by long-term genetic and psychological damage. By exploring the interaction between microRNA (miRNA), mRNA, and long non-coding RNA (lncRNA) in these patients, it is possible to identify gene expression patterns that could reduce cancer risk or improve treatment outcomes.

The purpose of this study is to examine transcriptome data from PBMC samples obtained from sulfur mustard exposed patients (Mild, Moderate, Severe) and healthy Control, separated into six groups (SC, SMo, SMi, MoMi, MoC, and MiC). miRNA, lncRNA, and mRNA interactions were explored using miRNA, lncRNA, and mRNA tools and databases, such as miRTarBase, miRDB, miRNET, miRcode, and DIANA. A tripartite mRNA-miRNA-lncRNA network was modeled with the aid of Cytoscape software, and functional analyses were performed to gain an understanding of molecular pathways using GO and KEGG functional analyses.

By extracting miRNAs shared between lncRNAs and mRNAs, six groups were identified and Cytoscape software was used to visualize the lncRNA-miRNA-mRNA network. Betweenness, closeness, and degree filters identified key genes, with INO80D and lncRNAs MINCR, LINC00662, NEAT1, and DHRS4-AS1, along with miRNAs hsa-miR-1-3p, hsa-miR-124-3p, and hsa-let-7b-5p as the main players in all groups.

The interaction between key genes involved in chemical injuries and their association with genes implicated in lung cancer is highlighted in this study. By targeting these genes and their proteins, we can improve treatment strategies for sulfur mustard exposed patients and potentially reduce lung cancer risk.

The expression level of long non-coding RNA (lncRNA), which functions in a manner similar to that of microrNA, has been confirmed to be closely associated with the regulatory network of multiple cancers. The primary focus of this particular research endeavor was to elucidate the mechanism of action of LINC01232 within the context of prostate cancer, specifically examining how it influences the proliferation of prostate cancer cells by interacting with the miR-181a-5p/IRS2 pathway. Additionally, the study aimed to delve deeper into the role of the Ki-67 protein within this intricate process. To assess the expression and localization of the Ki-67 protein in prostate cancer cells, researchers employed a combination of immunofluorescence and immunohistochemistry techniques. The expression level of Ki-67 protein decreased significantly after down-regulation of LINC01232, indicating that the cell proliferation activity was inhibited. Immunofluorescence and immunohistochemical experiments further confirmed that the expression of Ki-67 protein in prostate cancer cells was positively correlated with the expression of LINC01232.

Fungal keratitis (FK) is a challenging and sight-threatening corneal disease caused by fungal infections. Although long noncoding RNAs (lncRNAs) have been explored in various infectious diseases, their specific roles in FK remain largely unexplored.

A mouse model of FK was created by infecting corneal stromal cells with Fusarium solani. High-throughput lncRNA expression profiling was conducted on FK-affected corneal tissues to identify differentially expressed lncRNAs. Reverse transcription quantitative PCR (RT-qPCR) was used to validate the results. A competing endogenous RNA (ceRNA) network was constructed. Additionally, a specific antisense oligonucleotide (ASO) targeting lncRNA ENSMUST00000226838/Osr2 (Osr2) was developed for therapeutic evaluation. Inflammatory markers IL-1β, IL-6, and TNF-α were measured, and corneal inflammation was assessed through histological analysis and slit-lamp examination. Fluorescent in situ hybridization (FISH) was used to confirm Osr2 localization, whereas a dual-luciferase reporter assay verified interactions between Osr2 and miR-30a-3p.

We identified 1143 differentially expressed lncRNAs in FK, with 701 upregulated and 442 downregulated. The ceRNA network analysis indicated that lncRNA Osr2 regulates Xcr1 expression through miR-30a-3p. Treatment with ASO-Osr2 significantly reduced corneal inflammation, and FISH confirmed lncRNA Osr2 distribution in both the nucleus and cytoplasm. Dual-luciferase assays demonstrated the interaction between Osr2 and miR-30a-3p, highlighting their potential roles in the progression of FK.

This study outlined the lncRNA expression profile in FK and established a ceRNA regulatory network, identifying lncRNA Osr2 as a crucial modulator of FK pathogenesis through its interaction with miR-30a-3p. These findings highlighted lncRNA Osr2 as a promising therapeutic target for the treatment of FK.

Cleft palate is the most prevalent congenital condition. Cleft palate is brought on by an exogenous chemical called all-trans retinoic acid (atRA). In order to indirectly control gene expression, long chain non-coding RNAs (lncRNAs) act as competitive endogenous RNA (ceRNA) sponges. Its exact mode of action in cleft palate has not yet been determined. The purpose of this study was to determine whether lncRNAs and miRNAs regulated palatal fusion genes during the formation of cleft palate and to offer a possible course for cleft palate target gene therapy. In this work, we created a cleft palate model using atRA, conducted RNA sequencing (RNA-seq) to identify the genes that differed between the atRA-treated group and the control group, and built the lncRNA-miRNA-mRNA ceRNA network based on the projected ceRNA. The results were confirmed using a quantitative real-time polymerase chain reaction (qRT-PCR). ENSMUST00000159153-miR-137-5p-Wnt7a and ENSMUST000000236086-miR-34b-3p-EphA10/TRPM2 may be the main causes of atRA-induced cleft palate, according to the results.

Chemoresistance poses a significant challenge in the treatment of osteosarcoma (OS). Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of cancer biology. Despite accumulating evidence linking dysregulation of lncRNAs to chemoresistance, the specific regulatory functions and complexities involved in lncRNA-mediated modulation of doxorubicin-based chemotherapy in OS remain understudied.

We examined expression levels of lncRNA Lnc-PHF3-3 and miR-142-3p in OS tissues and cell lines by lncRNA microarray profiling and qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of lncRNA Lnc-PHF3-3 and miR-142-3p on chemoresistance of OS cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of Lnc-PHF3-3 in OS cells.

This study aimed to investigate key lncRNAs associated with chemoresistance in OS and identify potential therapeutic targets for patients with chemoresistant OS. To identify chemoresistance-related lncRNAs, microarray analysis was conducted using drug-resistant/drug-sensitive OS cell lines and chemoresistant/chemosensitive OS tissues. Among the identified candidates, a novel lncRNA called Lnc-PHF3-3 was found to be upregulated in doxorubicin-resistant OS cell lines and chemoresistant OS patients. Functional characterization revealed that Lnc-PHF3-3 promoted doxorubicin resistance both in vitro and in vivo. Further investigation revealed that Lnc-PHF3-3 acted as a sponge for microRNA miR-142-3p, and overexpression of miR-142-3p resulted in reduced chemoresistance. Additionally, the high mobility group box 1 (HMGB1) gene was identified as a direct and functional target of miR-142-3p.

We conclude that Lnc-PHF3-3 contributes to doxorubicin resistance in OS by sequestering miR-142-3p and subsequently enhancing HMGB1 expression.

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder with elusive molecular mechanisms. This study explores the competitive endogenous RNA (ceRNA) regulatory network in the cumulus cells of PCOS patients. ceRNAs are transcripts like mRNAs, miRNAs, and lncRNAs that competitively bind shared miRNAs, regulating gene expression post-transcriptionally. We analyzed mRNA, microRNA (miRNA), and long non-coding RNA (lncRNA) from two cohorts: 12 PCOS patients and 11 healthy controls (dataset GSE10946), and 5 PCOS patients and 5 healthy controls (dataset GSE72274). These microarray datasets, obtained from the Gene Expression Omnibus (GEO), helped us identify differentially expressed mRNAs, miRNAs, and lncRNAs. Our analysis revealed a significant ceRNA network, which may play a crucial role in the pathophysiology of PCOS. In this network, 5 lncRNAs, 3 miRNAs, and 36 mRNAs were identified as differentially expressed. These elements form a complex regulatory schema influencing key cellular processes related to the disease, such as cell cycle regulation and response to estrogen. The HOXA11-AS-hsa-miR-454-3p-CCND2 network emerged as a potentially valuable biomarker for PCOS diagnosis, supported by Receiver Operating Characteristic (ROC) curve analysis indicating strong predictive power. Our findings suggest that the ceRNA interactions in PCOS cumulus cells provide a deeper understanding of the disease's molecular basis and offer new avenues for therapeutic intervention. This in silico study lays the groundwork for further experimental validation of these ceRNA networks as targets for PCOS treatment.

Puberty is a crucial developmental stage marked by the transition from childhood to adulthood, organized by complex hormonal signaling within the neuroendocrine system. The hypothalamus, a central region in this system, regulates pubertal functions through the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons, essential in puberty control, release GnRH in a pulsatile manner, initiating the production of sex hormones. Major influence in pubertal timing has been attributed to genetic predisposition, environmental factors, and nutritional status. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as key regulators in various cellular processes by either repressing genes or activating them by inhibiting their repressors. The present study aims to investigate the involvement of miRNAs in the control of puberty.

Small RNA sequencing was used to identify and compare the total population of miRNAs in the hypothalamus of female mice before, during and after puberty. Bioinformatic analysis was applied to analyse the expression profile of miRNAs with altered levels followed by pathway enrichment analysis.

Expression levels of several miRNAs were found up- or down-regulated from pre-pubertal to pubertal stage. Furthermore, monitoring the levels of these miRNAs at the post-pubertal stage revealed four expression patterns, in which pathway analysis displayed the associations of these miRNAs with developmental processes, cell cycle regulation, metabolic biosynthesis and epigenetic regulation.

The findings of the present study improve our understanding of the molecular pathways underlying puberty and stress the significance of miRNAs in fine-tuning gene expression within the hypothalamus during this critical developmental stage.

Different diseases may arise from the dysregulation of non-coding RNAs (ncRNAs), which regulation is necessary for maintaining cellular homeostasis. ncRNAs are regulated by transcriptional, post-transcriptional, translational and post-translational processes. Post-transcriptional regulation of gene expression is carried out by microRNAs (miRNAs), a class of small ncRNA molecules, which can identify their target sites by a brief nucleotide sequence, known as the miRNA response element (MRE), present on the miRNA seed sequence and the target transcript. This binding between miRNAs and targets can regulate the gene expression through inhibition of translation or degradation of target messenger RNA (mRNA). The transcripts that share MREs can be involved in competition for the central miRNA pool, which could have an indirect impact on each other's regulation. This competition network is called competing endogenous RNAs network (ceRNET). Many ncRNAs, including circular RNA, pseudogene, and long non-coding RNA, as well as mRNA, a coding RNA transcript, make up ceRNET. These components play a crucial role in post-transcriptional regulation and are involved in the diagnosis and treatment of many pathological disorders. The mechanism of ceRNET and its essential components, as well as their therapeutic implications in different diseases such as cancer, diabetes mellitus, neurological, cardiovascular, hepatic and respiratory disorders were covered in this review.

Fibrosis is a common late complication of radiation therapy. Molecular dysregulations leading to fibrosis have been characterized for the coding part of the genome, notably those involving the TGFB1 gene network. However, because a large part of the human genome encodes RNA transcripts that are not translated into proteins, exploring the involvement of the noncoding part of the genome in fibrosis susceptibility and development was the aim of this work.

Breast cancer patients having or not having developed severe breast fibrosis after radiation therapy were retrospectively selected from the COPERNIC collection. Exome sequencing and RNA-seq transcriptomic profiling were performed on 19 primary dermal fibroblast strains isolated from the patients' nonirradiated skin. Functional experiments were based on fibrogenic induction by transforming growth factor-Beta1 (TGFB1) and gene knockdown in healthy donor fibroblasts.

Coding and noncoding transcriptomes discriminated fibrosis from nonfibrosis conditions, and a signature of breast fibrosis susceptibility comprising 15 long noncoding RNAs (lncRNAs) was identified. A hazard ratio validation showed that the lncRNA vimentin antisense long noncoding RNA 1 (VIM-AS1) was the best biomarker associated with fibrosis risk. This lncRNA has not been previously associated with any fibrotic disorder, but we found it upregulated in data sets from cardiac fibrosis and scleroderma, suggesting a general role in tissue fibrosis. Functional experiments demonstrated a profibrotic action of VIM-AS1 because its knockdown reduced myofibroblast activation, collagen matrix production, and dermal organoid contraction. RNA-seq data analysis after VIM-AS1 silencing also pointed out the regulation of replication, cell cycle, and DNA repair. Mechanistically, because VIM-AS1 was found coregulated with the vimentin gene, these data support a profibrotic function of the TGFB1/VIM-AS1/vimentin axis, targeting the dynamics of fibroblast-myofibroblast transition.

Noncoding RNA analysis can provide specific biomarkers relevant to the prediction of normal tissue responses after radiation therapy, which opens perspectives of next-generation approaches for treatment, in the frame of the recent developments of RNA-based technologies.

As cold-blooded vertebrates, fish are sensitive to environmental changes. The outcome of pathogen infections in fish therefore is highly shaped by hypoxia. The epigenetic regulation of competitive endogenous RNA (ceRNA) bridging non-coding RNAs and mRNAs represents a promising mechanism modulating antibacterial response plus environmental stress. Here, we for the first time systematically analyzed the ceRNA crosstalk in fish response to the combined stimulation of hypoxia and bacterial infection (HB) dual-stimulation. We found that mitochondrial apoptosis initiated by loss of mitochondrial membrane potential was the main causative for liver damage induced by HB challenge in fish. Accordingly, through whole transcriptome analysis, an apoptosis-associated ceRNA network was constructed, based on which a key crosstalk consisting of lnc432, miR-21-y and DAPK2 was identified. Mechanistically, DAPK2 acted as a positive regulator, knockdown of which significantly increased the bacterial burden during hypoxia by promoting mitochondrial apoptosis. MiR-21-y inhibited DAPK2 expression at both mRNA and protein levels by interacting with its 3'UTR, thereby enhancing DAPK2-mediated apoptosis determinations, and exacerbating bacterial infection during hypoxia. Lnc432 knockdown significantly increased miR-21-y and decreased DAPK2, and substantially promoted the expression of genes associated with mitochondrial apoptosis and enhanced the bacterial load during hypoxia stress. Finally, we revealed that lnc432 sponged miR-21-y to alleviate its suppression on DAPK2 in the ceRNA regulatory way. Our findings reveal that lnc432-miR-21-y-DAPK2 ceRNA crosstalk occurs in fish response to bacterial infection during hypoxic stress through mediating mitochondrial apoptosis. This study provides novel insights into the mechanism underlying the interactions among pathogens, hosts and environmental factors.

Histone acetylation, particularly H3 K27 acetylation (H3K27ac), is a critical post-translational modification that regulates chromatin structure and gene expression, which plays a significant role in various cancers, including breast, colon, lung, hepatocellular, and prostate cancer. However, the mechanisms of H3K27ac in tumorigenesis are not yet comprehensive, especially its epigenetic mechanisms. This review endeavors to discuss findings on the involvement of H3K27ac in carcinogenesis within the past 5 years through a literature search using academic databases such as Web of Science. Firstly, we provide an overview of the diverse landscape of histone modifications, emphasizing the distinctive characteristics and critical significance of H3K27ac. Secondly, we summarize and compare advanced high-throughput sequencing technologies that have been utilized in the construction of the H3K27ac epigenetic map. Thirdly, we elucidate the role of H3K27ac in mediating gene transcription. Fourthly, we venture into the potential molecular mechanism of H3K27ac in cancer development. Finally, we engage in discussing future therapeutic approaches in oncology, with a spotlight on strategies that harness the potential of H3K27 modifications. In conclusion, this review comprehensively summarizes the characteristics of H3K27ac and underscores its pivotal role in cancer, providing valuable insights into its potential as a therapeutic target for cancer intervention.

Circular RNAs (circRNAs) are a class of novel RNA molecules featured by single-strand covalently closed circular structure, which not only are extensively found in eukaryotes and are highly conserved, but also conduct paramount roles in the occurrence and progression of pancreatic cancer (PC) through diverse mechanisms. As recent studies have demonstrated, circRNAs typically exhibit tissue-specific and cell specific expression patterns, with strong potential as biomarkers for disease diagnosis and prognosis. On the basis of their localization and specific interactions with DNA, RNA, and proteins, circRNAs are considered to possess specific biological functions by acting as microRNA (miRNA) sponges, RNA binding protein (RBP) sponges, transcriptional regulators, molecular scaffolds and translation templates. On that account, further addressing the technical difficulties in the detection and research of circRNAs and filling gaps in their biological knowledge will definitely push ahead this comparatively young research field and bring circRNAs to the forefront of clinical practice. Thus, this review systematically summarizes the biogenesis, function, molecular mechanisms, biomarkers and therapeutic targets of circRNAs in PC.

The mean survival of metastatic lung adenocarcinoma is less than 1 year, highlighting the urgent need to understand the mechanisms underlying its high mortality rate. The role of Extracellular vesicles (EVs) in facilitating the interactions between cancer cells and the metastatic microenvironment has garnered increasing attention. Previous studies on the role of EVs in metastasis have been primarily focused on cancer cell-derived EVs in modulating the functions of stromal cells. However, whether cancer stem cells (CSCs) can alter the metastatic properties of non-CSC cells, and whether EV crosstalk can mediate such interaction, have not been demonstrated prior to this report. In the present study, we integrated multi-omics sequencing and public database analysis with experimental validation to demonstrate, for the first time, the exosomal Mir100hg, derived from CSCs, could enhance the metastatic potential of non-CSCs both in vitro and in vivo. Mechanistically, HNRNPF and HNRNPA2B1 directly binds to Mir100hg, facilitating its trafficking via exosomes to non-CSCs. In non-CSCs, Mir100hg upregulates ALDOA expression, subsequently leading to elevated lactate production. Consequently, the increased lactate levels enhance H3K14 lactylation by 2.5-fold and promote the transcription of 169 metastasis-related genes. This cascade of events ultimately results in enhanced ALDOA-driven glycolysis and histone lactylation-mediated metastatic potential of non-CSC lung cancer cells. We have delineated a complex regulatory network utilized by CSCs to transfer their high metastatic activity to non-CSCs through exosomal Mir100hg, providing new mechanistic insights into the communication between these two heterogeneous tumor cell populations. These mechanistic insights provide novel therapeutic targets for metastatic lung cancer, including HNRNPF/HNRNPA2B1-mediated Mir100hg trafficking and the histone lactylation pathway, advancing our understanding of CSC-mediated metastasis while suggesting promising strategies for clinical intervention.

Fusarium head blight (FHB), caused primarily by Fusarium graminearum (Fg), poses a significant threat to wheat production. It is necessary to deeply understand the molecular mechanisms underlying FHB resistance in wheat breeding.

In this study, the transcriptomic responses of two Chinese wheat landraces-Wuyangmai (WY, resistant) and Chinese Spring (CS, susceptible)-to F. graminearum infection were examined using RNA sequencing (RNA-seq). Differential expression of mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) was analyzed at 3 and 5 days post-Fg inoculation (dpi).

The results showed that WY exhibited a targeted miRNA response, primarily modulating defense-related pathways such as glutathione metabolism and phenylpropanoid biosynthesis, which are crucial for oxidative stress regulation and pathogen defense response. In contrast, CS displayed a broader transcriptional response, largely linked to general metabolic processes rather than immune activation. Notably, the up-regulation of genes involved in oxidative stress and immune defense in WY confirmed its enhanced resistance to FHB. The integrated analysis of miRNA-mRNA interactions highlighted miRNAs as central regulators of defense mechanisms in WY, particularly at later stages of infection. These miRNAs targeted genes involved in immune responses, while lncRNAs and circRNAs played a more limited role in the regulation of defense responses. The GO and KEGG pathway enrichment analyses further revealed that WY enriched for plant-pathogen interaction and secondary metabolite biosynthesis pathways, which are crucial for pathogen resistance. In contrast, CS prioritized metabolic homeostasis, suggesting a less effective defense strategy.

Overall, this study underscores the critical role of miRNA-mediated regulation in FHB resistance in WY. These insights into miRNA-mediated regulatory mechanisms provide a molecular basis for breeding FHB-resistant wheat varieties and highlight miRNA-mRNA interactions as promising targets for enhancing disease resilience.

As a common and complex mental disorder, major depressive disorder (MDD) has brought a huge burden and challenges globally. Although the incidence of female MDD is twice that of male MDD, there are still no accurate diagnostic and treatment criteria for female MDD. The potential of long non-coding RNAs (lncRNAs) as efficient and accurate diagnostic and therapeutic biomarkers provides more possibilities for early and accurate diagnosis of MDD.

First, the differential expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs) between MDD patients and healthy controls was established based on high-throughput sequencing analysis. Then, the potential biomarker was screened out by quantifying differentially expressed lncRNAs based on quantitative real-time PCR. To further investigate the function of biomarkers in the pathogenesis of MDD, bioinformatics analysis on downstream target genes was carried out.

The expression profile screened out 300 differentially expressed lncRNAs. HYMAI was proved to be the potential diagnostic biomarker. Its expression levels were significantly higher in MDD patients than in healthy controls with high potential diagnostic value. Based on bioinformatics analysis, a HYMAI-miRNA-mRNA network and a protein-protein interaction network were established, which also showed that HYMAI is closely related to MDD.

Our findings showed that the dysregulated expression of lncRNA HYMAI may be the pathophysiological basis of women suffering from MDD. Here, insight into the molecular mechanism of women's susceptibility to MDD is shown. Meanwhile, a new perspective for future female MDD prevention, diagnosis and treatment, evaluation, detection, and intervention is provided.

Stomach adenocarcinoma (STAD) has high incidence and mortality rates. Long non-coding RNAs (lncRNAs) and angiogenesis are closely related to the pathogenesis and metastasis of STAD. Recently, emerging evidence demonstrated that DNA methylation plays crucial roles in the development of STAD. This study explored the relationship between DNA methylation and the abnormal expression of angiogenesis-related lncRNAs (ARlncRNAs) in stomach adenocarcinoma, aiming to identify prognostic biomarkers. Moreover, a Cox analysis and Lasso regression were used to establish an ARlncRNA feature set related to angiogenesis. The prognostic model was evaluated by using a Kaplan-Meier (KM) analysis, ROC curves, and nomograms. Based on the identified 18 key ARlncRNAs, a prognostic predictive model was constructed. In addition, a specific ARlncRNA with abnormal methylation in the model, LINC00511, showed significant differences in expression and methylation across different subgroups. The methylation and expression of LINC00511 were analyzed by a correlation and co-expression analysis. The correlation analysis indicated that promoter methylation may improve LINC00511 expression. Further analysis found 355 mRNAs co-expressed with LINC00511 which may interact with 6 miRNAs to regulate target gene expression. The abnormal methylation of LINC00511 could significantly contribute to the progression of stomach adenocarcinoma.

The current study demonstrated that oxidative stress (OS) is closely related to the pathogenesis of polycystic ovary syndrome (PCOS). However, there are numerous factors that lead to OS, therefore, identifying the key genes associated with PCOS that contribute to OS is crucial for elucidating the pathogenesis of PCOS and selecting appropriate treatment strategies.

Four datasets (GSE95728, GSE106724, GSE138572, and GSE145296) were downloaded from the gene expression omnibus (GEO) database. GSE95728 and GSE106724 were combined to identify differentially expressed genes (DEGs) in PCOS. weighted gene correlation network analysis (WGCNA) was used to screen key module genes associated with PCOS. Differentially expressed OS related genes (DE-OSRGs) associated with PCOS were obtained by overlapping DEGs, key module genes, and OSRGs. Subsequently, the optimal machine model was obtained to identify key genes by comparing the performance of the random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM). The molecular networks were constructed to reveal the non-coding regulatory mechanisms of key genes based on GSE138572 and GSE145296. The Drug-Gene Interaction Database (DGIdb) was used to predict the potential therapeutic agents of key genes for PCOS. Finally, the expression of key OSRGs was validated by RT-PCR.

In this study, 8 DE-OSRGs were identified. Based on the residuals and root mean square error of the three models, the best performance of RF was derived and 7 key genes (TNFSF10, CBL, IFNG, CP, CASP8, APOA1, and DDIT3) were identified. The GSEA enrichment analysis revealed that TNFSF10, CP, DDIT3, and INFG are all enriched in the NOD-like receptor signaling pathway and natural killer cell-mediated cytotoxicity pathways. The molecular regulatory network uncovered that both TNFSF10 and CBL are regulated by non-coding RNAs. Additionally, 70 potential therapeutic drugs for PCOS were predicted, with ibuprofen associated with DDIT3 and IFNG. RT-qPCR validation confirmed the expression trends of key genes IFNG, DDIT3, and APOA1 were consistent with the dataset, and the observed differences were statistically significant (P < 0.05).

The identification of seven key genes and molecular regulatory networks through bioinformatics analysis is of great significance for exploring the pathogenesis and therapeutic strategies of PCOS.

Long noncoding RNAs (lncRNAs) HIF1A-AS2 is upregulated in multiple human cancers and are associated with various aspects of tumor progression. However, the molecular mechanisms of HIF1A-AS2 in cervical cancer (CC) remain largely unknown. In this study, we aim to investigate the expression pattern and signaling pathways of HIF1A-AS2 in CC.

The study included a group of 20 CC patients, from whom tumor tissue specimens were collected. Additionally, three distinct CC cell lines (HeLa, SiHa, CaSki) were utilized. Quantitative real-time PCR (qRT-PCR) was used to assess the transcript levels of HIF1A-AS2 in these samples. Functional studies were performed by CCK-8, Transwell and Apoptosis assays. Databases including JASPAR, miRDB and Targetscan were used for the transcription factor or target miRNA prediction, subsequent dual luciferase activity assay, chromatin immunoprecipitation (ChIP) and Ago2 immunoprecipitation (RIP) were also adopted for validation.

The study demonstrated that HIF1A-AS2 expression was elevated in clinical cervical cancer specimens and cultured cell lines in comparison to normal controls. Knockdown of HIF1A-AS2 notably inhibited the proliferation and invasion of cervical cancer cells, while inducing apoptosis. In contrast, HIF1A-AS2 overexpression promoted cellular proliferation and invasion and suppressed apoptosis. It was also identified that c-Jun functions as a transcription factor, activating HIF1A-AS2 expression. Additionally, HIF1A-AS2 was found to serve as a molecular sponge for miR-34b-5p, negatively regulating its expression. Furthermore, HIF1A-AS2 controlled the expression of radixin (RDX) by sponging the miR-34b-5p pathway.

Our findings indicate that c-Jun-activated HIF1A-AS2 acts as an oncogenic factor in CC by sponging miR-34b-5p to target radixin. These findings suggest that HIF1A-AS2 might be a viable and promising therapeutic target for cervical cancer treatment.

Cancer remains a major global health challenge, with prostate cancer, lung cancer, colorectal cancer, and breast cancer accounting for nearly half of all diagnoses. Despite advancements in cancer treatment, metastasis to distant organs continues to be the leading cause of cancer-related mortality. The progression of cancer involves the alteration of numerous genes, with dynamic changes in chromatin organization and histone modifications playing a critical role in regulating cancer-associated genes. Special AT-rich sequence-binding protein 1 (SATB1), a critical chromatin organizer, plays a pivotal role in cancer progression by regulating gene expression, chromatin remodeling, and cell signaling pathways. SATB1 binds to AT-rich DNA sequences, acting as a scaffold for chromatin-modifying enzymes and transcription factors, thus coordinating the regulation of extensive gene networks. Its overexpression has been implicated in a wide range of cancers and is associated with poor prognosis, aggressive tumor phenotypes, and enhanced epithelial-mesenchymal transition (EMT). Moreover, SATB1's activity is modulated by microRNAs (miRNAs) and post-translational modifications, further contributing to its complex regulatory functions. Given its crucial involvement in cancer progression and metastasis, SATB1 has emerged as a promising target for novel therapeutic strategies. This review delves into the molecular mechanisms of SATB1 in cancer and explores potential therapeutic approaches for targeting this key regulator in cancer treatment.

This study investigates the regulatory function of circular RNA (circRNA) as a competing endogenous RNA (ceRNA) in rice (Oryza sativa L.) under toxic levels of copper (Cu) stress. Physiological parameters and differences in Cu accumulation were analyzed through a hydroponic experiment. RNA sequencing (RNA-seq) identified 1051 circRNAs, of which 26 were differentially expressed (FDR <0.05, |log2FC| > 1) under Cu stress. A Cu-responsive ceRNA network mediated by circRNAs was constructed, comprising 16 circRNAs, 34 miRNAs, and 126 mRNAs. Topological analysis identified the circGDSL/miR1850.1/OPR3 triplet as a key regulatory hub, which was experimentally validated by RT-qPCR. Overexpression of circGDSL conferred significant resistance to Cu stress, characterized by enhanced antioxidant enzyme activity, reduced reactive oxygen species (ROS) levels, and alleviated Cu-induced growth suppression. Functional studies indicated that circGDSL upregulates the expression of the key jasmonic acid (JA) synthesis gene OPR3 by sponging miR1850.1, thereby activating the JA signaling pathway. The increased endogenous JA concentration represses the expression of genes (IRT1, Nramp5, and HMA2) that promote Cu uptake and translocation, resulting in decreased Cu concentration in rice. Conversely, overexpression of miR1850.1 reduces endogenous JA concentration and increases sensitivity to Cu, a phenotype that can be rescued by exogenous methyl jasmonate (MeJA). In conclusion, we identified a Cu-responsive circRNA in rice and confirmed its role in activating JA synthesis pathway as miRNA sponge, thereby enhancing rice tolerance to Cu stress.

The specific role of efferocytosis-related long noncoding RNAs (ERLncRNAs) in Clear Cell Renal Cell Carcinoma (ccRCC) has not been thoroughly examined. This study aims to identify and validate a signature of ERLncRNAs for prognostic prediction and characterization of the immune landscape in individuals with ccRCC.

Analysis of ccRCC samples was conducted by utilizing clinical and RNA sequencing information obtained from The Cancer Genome Atlas (TCGA). Pearson correlation analysis was utilized to identify lncRNAs associated with efferocytosis, which was then used to create a new prognostic model through univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and stepwise multivariate Cox analysis. In order to investigate the biological significance, we performed a functional enrichment analysis to assess how well the model predicts outcomes. Differences in the immune landscape were observed through a comparison of immune cell infiltration, tumor mutational burden (TMB), and tumor microenvironment (TME) characteristics. Following this, drug sensitivity analysis was conducted.

This led to the identification of a unique signature consisting of seven ERLncRNAs (LINC01615, RUNX3-AS1, FOXD2-AS1, AC002070.1, LINC02747, LINC00944, and AC092296.1). Model performance was measured by Kaplan-Meier curves and receiver operating characteristic (ROC) curves. The nomogram and C-index provided additional validation of the strong correlation between the risk signature and clinical decision-making.

On the whole, our innovative signature exhibits potential for prognostic prediction and assessment of immunotherapeutic response in patients with ccRCC.

AbstractImmunosuppression induced by infectious bursal disease virus (IBDV) and its subsequent secondary infections remain the serious problems that urgently need to be addressed in poultry industry. Even more troubling, the molecular mechanism of IBDV-induced immunosuppression is not fully understood. In this study, expression characteristics of immune checkpoint programmed cell death-ligand 1 (PD-L1) gene were explored in chicken immune response induced by IBDV attenuated vaccine, and the competing endogenous RNA (ceRNA) regulatory mechanism of PD-L1 gene in vivo was identified by quantitative real-time PCR (qRT-PCR). The results showed that PD-L1 gene expressions were closely related to the immune response to IBDV, and played important regulatory roles in the immune-related tissues at different stages of the immune response. Significant game relationships in expression levels between miR-17 family members (miR-17-5p, miR-20a-5p, and miR-20b-5p), circITSN2, and PD-L1 gene were identified in vivo, so the circITSN2-miR-17-5p/20a-5p/20b-5p-PD-L1 network was a potential molecular regulatory mechanism of PD-L1 in the immune response to IBDV vaccine, and heart (5 dpi), proventriculus (5 dpi), and lung (21 dpi) were the key tissues. This study can provide valuable references for further studying the molecular mechanisms of immunosuppression induced by IBDV.

Ischemic stroke (IS) is a severe and sudden cerebrovascular event, associated with notably high rates of mortality and morbidity. The process of apoptosis, a genetically orchestrated form of programmed cell death, is divided into two pathways: intrinsic and extrinsic. The intricate involvement of long non-coding RNA (lncRNA) in the pathobiology of IS, particularly in modulating neuronal apoptosis, is a burgeoning area of research. This review synthesizes the current understanding of the regulatory mechanisms of lncRNA on neuronal apoptosis in the context of ischemic stroke. Specifically, we highlight the roles of lncRNA such as ANRIL, C2dat1/2, H19, TUG1, MEG3, SNHG, and GAS5, which have been implicated in the facilitation of neuronal apoptosis. Conversely, the lncRNA N1LR has been shown to exert an inhibitory effect on this process. The role of MALAT1 in neuronal apoptosis remains a subject of ongoing debate, as its function oscillates between pro-apoptotic and anti-apoptotic roles, thus highlighting the need for further elucidation.