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Cervical cancer (CC) poses a threat to human health. Enhancing pyroptosis can prevent the proliferation and epithelial–mesenchymal transition (EMT) of tumor cells. This study aims to reveal the candidates that modulate pyroptosis in CC. Accordingly, the common microRNAs (miRNAs/miRs) that were sponged by RBPMS antisense RNA 1 (RBPMS‐AS1) and could target Phospholipase C–Like 1 (PLCL1) were intersected. The expression of PBPMS‐AS1/miR‐19a‐3p (candidate miRNA)/PLCL1 was predicted in cervical squamous cell carcinoma (CESC), by which the expression location of RBPMS‐AS1 and the binding between RBPMS‐AS1/PLCL1 and miR‐19a‐3p were analyzed. The targeting relationship between RBPMS‐AS1/PLCL1 and miR‐19a‐3p was confirmed by dual‐luciferase reporter assay. After the transfection, cell counting kit‐8 assay, colony formation assay, quantitative reverse transcription PCR, and Western blot were implemented for cell viability and proliferation analysis as well as gene and protein expression quantification analysis. Based on the results, RBPMS‐AS1 and PLCL1 were lowly expressed, yet miR‐19a‐3p was highly expressed in CESC. RBPMS‐AS1 overexpression diminished the proliferation and expressions of N‐cadherin, vimentin, and miR‐19a‐3p, yet enhanced those of E‐cadherin, PLCL1, and pyroptosis‐relevant proteins (inteleukin‐1β, caspase‐1, and gasdermin D N‐terminal). However, the above RBPMS‐AS1 overexpression–induced effects were counteracted in the presence of miR‐19a‐3p. There also existed a targeting relationship and negative interplay between PLCL1 and miR‐19a‐3p. In short, RBPMS‐AS1 sponges miR‐19a‐3p and represses the growth and EMT of CC cells via enhancing PLCL1‐mediated pyroptosis. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a wide-spread gastrointestinal cancer that is associated with augmented morbidity and mortality, and we do not yet have a deep understanding of its epidemiology and carcinogenicity. The transcriptome can reveal the complexity and heterogeneity of tumors and uncover new biomarkers or treatment options. In this study, we identified messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), round RNAs (circRNAs), and microRNAs (miRNAs) using whole-transcriptome sequencing and generated competing endogenous RNA (ceRNA) modulatory axes. We conducted whole transcriptome sequencing on 10 CRC and para-cancer (CRCP) samples and discovered 2465 differentially expressed (DE) mRNAs (DEmRNAs), 77 DE miRNAs (DEmiRNAs). 2852 DE lncRNAs (DElncRNAs) and 1477 DE circRNAs (DEcircRNAs). In addition, utilizing co-DE analysis, we generated the ceRNA axis. Subsequently, we employed the ceRNA axis to identify essential genes and corresponding associations with lncRNAs, circRNAs, and miRNAs in CRC. ceRNA regulatory network including mRNA-miRNA-lncRNA and mRNA-miRNA-circRNA. These modulatory axes potentially modulate the positive regulation of smooth muscle contraction, melanosome, plasma membrane, integral plasma membrane component and so on. Finally, the results of RNA sequencing (RNA-SEQ) were combined with the TCGA and GEO databases, and the DEGs strongly correlated with the TCGA-COAD overall survival (OS) as estimated by univariate cox and logarithmic rank analyses were cross-analyzed, and the co-upregulated DEGs were screened. Among the many DEs, KPNA2 was chosen for additional analysis. Using invitro experimentations, western blot, CCK8, EdU and other experiments were performed to verify the results. We found siRNA-based KPNA2 depletion reduces bladder cancer cells' viability, migratory, and proliferative activities, which showed that the DEmRNA profiles were comparable to the sequencing information, confirming that the sequencing data were very reliable. These evidences highlight the ceRNA regulatory mechanisms in CRC and will aid future research into the molecular mechanisms behind colorectal cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Circular RNA (CircRNA)–microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted. [ABSTRACT FROM AUTHOR]

Nucleus pulposus cells survive in a hypoxic, acidic, nutrient-poor, and hypotonic microenvironment. Consequently, they maintain low proliferation and undergo autophagy to protect themselves from cellular stress. Therefore, we aimed to identify autophagy-related biomarkers involved in intervertebral disc degeneration pathogenesis. Autophagy-related differentially expressed genes were derived from the intersection between the public GSE147383 microarray data set to identify differentially expressed genes and online databases to identify autophagy-related genes. Furthermore, we assessed their biological functions with gene annotation and enrichment analysis in the Metscape portal. Then, the STRING database and Cytoscape software allowed inferring a protein-protein interaction (PPI) network and identifying hub genes. In addition, to predict transcription factors that may regulate the hub genes, we used the GeneMANIA website. Finally, the competing endogenous RNA prediction tools and Cytoscape were also used to construct an mRNA-miRNA-lncRNA network. A total of 123 autophagy-related differentially expressed genes were identified, they were mainly involved in phosphoinositide 3-kinase-Akt signaling, autophagy animal, and apoptosis pathways. Nine were identified as hub genes (PTEN, MYC, CTNNB1, JUN, BECN1, ERBB2, FOXO3, ATM, and FN1) and 36 transcription factors were associated with them. Finally, an autophagy-associated competing endogenous RNA network was constructed based on the 9 hub genes. Nine hub genes were identified and a network of competing endogenous RNA associated with autophagy was established. They can be used as autophagy-related biomarkers of intervertebral disc degeneration and for further exploration. [ABSTRACT FROM AUTHOR]

Dementia, a multifaceted neurological syndrome characterized by cognitive decline, poses significant challenges to daily functioning. The main causes of dementia, including Alzheimer's disease (AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and vascular dementia (VD), have different symptoms and etiologies. Genetic regulators, specifically non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are known to play important roles in dementia pathogenesis. MiRNAs, small non-coding RNAs, regulate gene expression by binding to the 3′ untranslated regions of target messenger RNAs (mRNAs), while lncRNAs and circRNAs act as molecular sponges for miRNAs, thereby regulating gene expression. The emerging concept of competing endogenous RNA (ceRNA) interactions, involving lncRNAs and circRNAs as competitors for miRNA binding, has gained attention as potential biomarkers and therapeutic targets in dementia-related disorders. This review explores the regulatory roles of ncRNAs, particularly miRNAs, and the intricate dynamics of ceRNA interactions, providing insights into dementia pathogenesis and potential therapeutic avenues. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC), an inflammatory bowel disease (IBD), may increase the risk of colorectal cancer (CRC) by activating chronic proinflammatory pathways. The goal of this study was to find serum prediction biomarkers in UC to CRC development by combining low-density miRNA microarray and biocomputational approaches. The UC and CRC miRNA expression profiles were compared by low-density miRNA microarray, finding five upregulated miRNAs specific to UC progression to CRC (hsa-let-7d-5p, hsa-miR-16-5p, hsa-miR-145-5p, hsa-miR-223-5p, and hsa-miR-331-3p). The circRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) network analysis showed that the candidate miRNAs were connected to well-known colitis-associated CRC ACVR2A, SOCS1, IGF2BP1, FAM126A, and CCDC85C mRNAs, and circ-SHPRH circRNA. SST and SCARA5 genes regulated by hsa-let-7d-5p, hsa-miR-145-5p, and hsa-miR-331-3p were linked to a poor survival prognosis in a CRC patient dataset from The Cancer Genome Atlas (TCGA). Lastly, our mRNA and miRNA candidates were validated by comparing their expression to differentially expressed mRNAs and miRNAs from colitis-associated CRC tissue databases. A high level of hsa-miR-331-3p and a parallel reduction in SOCS1 mRNA were found in tissue and serum. We propose hsa-miR-331-3p and possibly hsa-let-7d-5p as novel serum biomarkers for predicting UC progression to CRC. More clinical sample analysis is required for further validation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We aimed to analyze lncRNAs, miRNAs, and mRNA expression profiles of bladder cancer (BC) patients, thereby establishing a gene signature-based risk model for predicting prognosis of patients with BC. METHODS: We downloaded the expression data of lncRNAs, miRNAs and mRNA from The Cancer Genome Atlas (TCGA) as training cohort including 19 healthy control samples and 401 BC samples. The differentially expressed RNAs (DERs) were screened using limma package, and the competing endogenous RNAs (ceRNA) regulatory network was constructed and visualized by the cytoscape. Candidate DERs were screened to construct the risk score model and nomogram for predicting the overall survival (OS) time and prognosis of BC patients. The prognostic value was verified using a validation cohort in GSE13507. RESULTS: Based on 13 selected. lncRNAs, miRNAs and mRNA screened using L1–penalized algorithm, BC patients were classified into two groups: high-risk group (including 201 patients) and low risk group (including 200 patients). The high-risk group's OS time (hazard ratio [HR], 2.160; 95% CI, 1.586 to 2.942; P = 5.678e-07) was poorer than that of low-risk groups' (HR, 1.675; 95% CI, 1.037 to 2.713; P = 3.393 e-02) in the training cohort. The area under curve (AUC) for training and validation datasets were 0.852. Younger patients (age ⩽ 60 years) had an improved OS than the patients with advanced age (age > 60 years) (HR 1.033, 95% CI 1.017 to 1.049; p = 2.544E-05). We built a predictive model based on the TCGA cohort by using nomograms, including clinicopathological factors such as age, recurrence rate, and prognostic score. CONCLUSIONS: The risk model based on 13 DERs patterns could well predict the prognosis for patients with BC. [ABSTRACT FROM AUTHOR]

The etiology of epilepsy is ascribed to the synchronized aberrant neuronal activity within the brain. Circular RNAs (circRNAs), a class of non‐coding RNAs characterized by their circular structures and covalent linkage, exert a substantial influence on this phenomenon. CircRNAs possess stereotyped replication, transience, repetitiveness, and paroxysm. Additionally, MicroRNA (miRNA) plays a crucial role in the regulation of diverse pathological processes, including epilepsy. CircRNA is of particular significance due to its ability to function as a competing endogenous RNA, thereby sequestering or inhibiting miRNA activity through binding to target mRNA. Our review primarily concentrates on elucidating the pathological and functional roles, as well as the underlying mechanisms, of circRNA–miRNA–mRNA networks in epilepsy. Additionally, it explores the potential utility of these networks for early detection and therapeutic intervention. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common female reproductive endocrine disorder that is related with various factors including epigenetic and environment. Long non-coding RNA (lncRNA), with more than 200 nucleotides, are a kind of RNA molecules that do not code proteins. LncRNA can affect the expression of gene through epigenetic modification, transcriptional and post-transcriptional regulation. As a kind of competing endogenous RNA (ceRNA), lncRNA can affect the expression of target gene by competitively binding microRNA (miRNA). As a new regulatory mechanism, it can play an important role in many biological processes such as cell proliferation and differentiation, inflammatory response and immune response, which is closely related to many diseases. The ceRNA hypothesis also provides a further understanding of the mechanism of PCOS. Recently, the studies of lncRNA in PCOS significantly increased. The lncRNA differentially expressed in PCOS can involve as ceRNA in ovarian granulosa cell proliferation, oocyte maturation as well as hormone synthesis, and play an potential role in the development of PCOS. In this review, we summarize the roles of lncRNA as ceRNA in the occurrence and development of PCOS. [ABSTRACT FROM AUTHOR]

Low-temperature chilling is a major abiotic stress leading to reduced rice yield and is a significant environmental threat to food security. Low-temperature chilling studies have focused on physiological changes or coding genes. However, the competitive endogenous RNA mechanism in rice at low temperatures has not been reported. Therefore, in this study, antioxidant physiological indices were combined with whole-transcriptome data through weighted correlation network analysis, which found that the gene modules had the highest correlation with the key antioxidant enzymes superoxide dismutase and peroxidase. The hub genes of the superoxide dismutase-related module included the UDP-glucosyltransferase family protein, sesquiterpene synthase and indole-3-glycerophosphatase gene. The hub genes of the peroxidase-related module included the WRKY transcription factor, abscisic acid signal transduction pathway-related gene plasma membrane hydrogen-ATPase and receptor-like kinase. Therefore, we selected the modular hub genes and significantly enriched the metabolic pathway genes to construct the key competitive endogenous RNA networks, resulting in three competitive endogenous RNA networks of seven long non-coding RNAs regulating three co-expressed messenger RNAs via four microRNAs. Finally, the negative regulatory function of the WRKY transcription factor OsWRKY61 was determined via subcellular localization and validation of the physiological indices in the mutant. [ABSTRACT FROM AUTHOR]

Background: Lipid metabolism plays a pivotal role in asthma pathogenesis. However, a comprehensive analysis of the importance of lipid metabolism-related genes (LMRGs) in regulating the immune microenvironment in asthma remains lacking. The transcriptome matrix was downloaded from the Gene Expression Omnibus (GEO) dataset. Differentially expressed analysis and weighted gene coexpression network analysis (WGCNA) were conducted on the GSE74986 dataset to select hub LMRGs, and gene set enrichment analysis (GSEA) was conducted to explore their biological functions. The CIBERSORT algorithm was used to determine immune infiltration in the asthma and control groups, and the correlation of diagnostic biomarkers and immune cells was performed via Spearman correlation analysis. Subsequently, a competitive endogenous RNA (ceRNA) network was constructed to investigate the hidden molecular mechanism of asthma. The expression levels of the hub genes were further validated in the GSE143192 dataset, and RT‒qPCR and immunofluorescence were performed to verify the reliability of the results in the OVA asthma model. Lastly, the ceRNA network was confirmed by qRT-PCR and RNAi experiments in the characteristic cytokine (IL-13)-induced asthma cellular model. Results: ASAH1, ACER3 and SGPP1 were identified as hub LMRGs and were mainly involved in protein secretion, mTORC1 signaling, and fatty acid metabolism. We found more infiltration of CD8+ T cells, activated NK cells, and monocytes and less M0 macrophage infiltration in the asthma group than in the healthy control group. In addition, ASAH1, ACER3, and SGPP1 were negatively correlated with CD8+ T cells and activated NK cells, but positively correlated with M0 macrophages. Within the ceRNA network, SNHG9-hsa-miR-615-3p-ACER3, hsa-miR-212-5p and hsa-miR-5682 may play crucial roles in asthma pathogenesis. The low expression of ASAH1 and SGPP1 in asthma was also validated in the GSE74075 dataset. After SNHG9 knockdown, miR-615-3p expression was significantly upregulated, while that of ACER3 was significantly downregulated. Conclusion: ASAH1, ACER3 and SGPP1 might be diagnostic biomarkers for asthma, and are associated with increased immune system activation. In addition, SNHG9-hsa-miR-615-3p-ACER3 may be viewed as effective therapeutic targets for asthma. Our findings might provide a novel perspective for future research on asthma. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a large class of endogenous single-stranded covalently closed RNA molecules. High-throughput RNA sequencing and bioinformatic algorithms have identified thousands of eukaryotic circRNAs characterized by high stability and tissue-specific expression pattern. Recent studies have shown that circRNAs play an important role in the regulation of physiological processes in the norm and in various diseases, including cardiovascular disorders. The review presents current concepts of circRNA biogenesis, structural features, and biological functions, describes the methods of circRNA analysis, and summarizes the results of studies on the role of circRNAs in the pathogenesis of hypertrophic cardiomyopathy, the most common inherited heart disease. [ABSTRACT FROM AUTHOR]

Oxygen is an essential factor for the body's metabolism and survival. Hypoxic adaptation refers to a series of local and systemic changes that occur in the body to adapt to the physiological or pathological phenomenon of hypoxia, reducing the impact of hypoxia. Competing endogenous RNA (ceRNA) refers to RNA molecules that share the same microRNA response elements (MREs) and competitively bind to microRNAs to regulate gene expression at the post- transcriptional level, thereby influencing the biological functions of cells. ceRNA is a complex network regulation mechanism that plays a role in cell proliferation and apoptosis, inflammatory responses, energy metabolism, muscle development, fat deposition, lipid metabolism, and other aspects. The article summarizes the biological functions and characteristics of long noncoding RNA (lncRNA), circular RNA (circRNA), and pseudogenes. It elucidates the validated roles of ceRNA in the biological functions associated with animal hypoxic adaptation, providing reference for the study of mammalian hypoxia adaptability. [ABSTRACT FROM AUTHOR]

Gastric cancer is a kind of tumor with strong heterogeneity. Long noncoding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors. In this study, we divided all TCGA gastric cancer patients into the whole, intestinal and diffuse cohorts for further analysis, and constructed competitive endogenous RNA network and evaluated immune cells using CIBERSORTx. The support vector machines recursive feature elimination (SVM-RFE) was used for screening significant signatures and the support vector machines (SVM) for establishing model predicting the lymph node metastasis. The performance of SVM model was good in the intestinal and diffuse cohort, while the model in the whole cohort was relatively poor. Some important co-expression patterns between immune cells and ceRNAs network indicated significant correlation CD70 with dendritic cells and so on. Our research inferred competing endogenous RNA network of lymph node metastasis and built an excellent predicting model. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear. Methods: We conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis. Results: TDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC. Conclusions: Our study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment. [ABSTRACT FROM AUTHOR]

The article focuses on revealing the regulatory potency of CKAP5 in Human Papillomavirus positive Head and Neck Squamous Cell Carcinoma (HPV+ HNSCC) through Competing Endogenous RNA (ceRNA) analysis. It is discussed that Utilizing high-throughput sequencing technology, the study identifies differential gene expression and constructs a ceRNA network, highlighting CKAP5 as a potential therapeutic target in HPV+ HNSCC, emphasizing its significance in disease progression and prognosis.

BACKGROUND: Osteoarthritis is one of the most common joint diseases. With the increasing global incidence and prevalence of osteoarthritis, effective early diagnosis and treatment of osteoarthritis have become an urgent problem. OBJECTIVE: To elucidate the important biological functions of long non-coding RNAs, circular RNAs and pseudogenes and their regulatory roles as competing endogenous RNAs in osteoarthritis pathogenesis to gain a comprehensive, in-depth and new understanding of the involvement of competing endogenous RNAs in osteoarthritis progression and to provide new clues for early diagnosis and treatment of osteoarthritis. METHODS: CNKI, PubMed, VIP and WanFang databases were searched for articles published before 2022. The search terms were “osteoarthritis, competing endogenous RNA, circular RNA, long non-coding RNAs, pseudogenes” in Chinese and English. RESULTS AND CONCLUSION: Non-coding RNAs with the same microRNA response elements, including long non-coding RNAs, cyclic RNAs and pseudogenes, are involved in the construction of a regulatory network of competing endogenous RNAs centered on microRNAs. Non-coding RNAs, cyclic RNAs and pseudogenes can act as competing endogenous RNAs to adsorb microRNAs through “sponge” so as to regulate gene expression. Long non-coding RNAs, cyclic RNAs and pseudogenes can act as competing endogenous RNAs to regulate the proliferation, apoptosis and autophagy of osteoarthritic chondrocytes, the synthesis and degradation of extracellular matrix and the occurrence of inflammatory events. The practical application of the regulatory network of competing endogenous RNA to the clinical setting still faces many challenges and problems. The research on competing endogenous RNA as diagnostic markers or therapeutic targets for osteoarthritis is still at an early stage, and the current research on competing endogenous RNA regulatory network is still focused on the identification and validation of individual competing endogenous RNAs, and this regulatory network needs to be further supplemented and improved. However, with the development of advanced technologies, competing endogenous RNAs are expected to become early diagnostic markers and therapeutic targets for osteoarthritis diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the change of disease treatment mode, people have realized the importance of traditional Chinese medicine in the treatment of steroidinduced necrosis of the femoral head (SANFH). Therefore, bioinformatics is used to analyze the pathogenesis of SANFH at the molecular level, build a disease risk model, and predict the potential therapeutic effects of traditional Chinese medicine, so as to provide a theoretical basis for the treatment of SANFH by traditional Chinese medicine in the future. OBJECTIVE: To mine the competing endogenous RNA regulatory network of SANFH based on bioinformatics, analyze its molecular regulatory mechanism in SANFH, predict relevant disease targets, build disease risk models, and predict Chinese herbal medicines with potential therapeutic effects. METHODS: The GEO database was searched to download the SANFH matrix file GSE123568 and gene annotation file GPL15207. The differentially expressed long non-coding RNAs and mRNAs were obtained by software analysis such as R language, and the miRNA-mRNAs associated with the differentially expressed long non-coding RNAs were predicted through the public database. Then, predicted and differentially expressed mRNAs were intersected and integrated to obtain the competing endogenous RNA network. STRING database and Cytoscape software were used to screen key genes and R language was used to analyze the functions and related pathways of key genes and mine the key competing endogenous RNA network. Finally, the risk model of SANFH was constructed according to the key genes and the prediction of traditional Chinese medicine was carried out. RESULTS AND CONCLUSION: Compared with healthy controls, a total of 7 long non-coding RNAs and 1763 mRNAs were differentially expressed in SANFH patients. Six key genes including STAT3, KAT2B, AGO4, JAK2, JAK1, and PTGS2 were identified. The enriched functions of key genes include biological processes such as response to peptide hormones, interleukin-6-mediated signaling pathways, and cell responses to interleukin-6, and are involved in signaling pathways such as JAK-STAT, adipocytokines, and prolactin. Four miRNAs (miR- 135a-5p, miR-137, miR-17-5p, miR-20b-5p) and two long non-coding RNAs (SNHG11, C20orf197) may play a key role in the occurrence and development of SANFH. KAT2B is most likely to be a risk factor for SANFH. Turmeric, Epimedium, and Astragalus have the potential to treat SANFH. Through the analysis of the competing endogenous RNA network mediated by SANFH-related long non-coding RNAs, potential disease targets, signaling pathways, and potential therapeutic traditional Chinese medicines can be identified, providing a reference for further clarifying its pathogenesis in subsequent experimental research. [ABSTRACT FROM AUTHOR]

Purpose: Immune disorders lead to placental dysfunction and fetal growth restriction (FGR), but current research on the immune regulation mechanisms of FGR and the involvement of competing for endogenous RNA (ceRNA) is insufficient. Therefore, this study aimed to construct an immune-related ceRNA network to predict FGR onset risk. Methods: Microarray data from the GEO database was used for gene expression and immune infiltration analyses. Weighted gene co-expression network analysis (WGCNA) was used to screen immune-related module genes with differential expression (DE) in FGR. A ceRNA network was constructed by integrating long non-coding RNA (lncRNA)-mRNA, lncRNA-microRNA (miRNA), and miRNA-mRNA relations. The diagnostic values of key genes in the network and their relationships with immune cell were confirmed in a validation cohort. Results: By comparing FGR and normal samples, DE mRNAs, miRNAs, lncRNAs, and four types of immune cells with different infiltration levels were obtained. WGCNA then revealed 236 immune-related DE mRNAs that were involved in hormone secretion and immune cell differentiation. Based on co-expression analysis and miRNA prediction, we initially constructed a ceRNA network to screen several immune-related genes as potential diagnostic biomarkers of FGR, whose superior predictive performances were further confirmed by receiver operating characteristic curves. Among them, NEURL1 and ODF3B were found to positively correlate with M1 macrophages and may participate in the immunoregulation of FGR. Conclusion: From the perspective of ceRNA mechanism, we constructed an immune-related regulatory network for the first time wherein key genes are initially proposed as potential diagnostic biomarkers of FGR to involve in M1 macrophage-mediated immunoregulation. [ABSTRACT FROM AUTHOR]

Normal articular cartilage plays an important role in limb movement. Joint trauma, biomechanical changes, age, and other risk factors lead to articular cartilage injury. Although previous studies have reported the causes of articular cartilage injury at the molecular level, the inter-molecular regulatory mechanisms of the occurrence and prognosis of cartilage injury are not fully understood. Competing endogenous RNAs (ceRNAs) are a huge inter-molecular regulatory network of RNAs, including non-coding RNAs (ncRNAs) and other molecules. As an emerging regulatory mechanism, ceRNAs participate in the injury and repair of articular cartilage. Studies have found that ceRNAs regulate the proliferation and apoptosis of articular chondrocytes and the degradation of cartilage extracellular matrix through competitive binding of microRNA (miRNA), thus affecting the health of articular cartilage. The authors refer to?the related?literature?and materials?in recent years to review the mechanism of action and potential application of ceRNA network in articular cartilage injury, in order to provide a new thought and direction for the prevention and treatment of articular cartilage injury. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) causes irreversible blindness in people aged over 50 worldwide. The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD. In the current study, we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database. We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis. Peroxisome and tumor necrosis factor-α (TNF-α) signaling and nuclear factor kappa B (NF-κB) were among the top 10 pathways, and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs (circRNAs). We then constructed a competing endogenous RNA network, which is related to differentially expressed circRNAs. This network included seven circRNAs, 15 microRNAs, and 82 mRNAs. The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxiainducible factor-1 (HIF-1) signaling pathway was a common downstream event. The results of the current study may provide insights into the pathological processes of atrophic AMD. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disease of the lung with poor prognosis. Fibrosis results from remodeling of the interstitial tissue. A wide range of gene expression changes are observed, but the role of micro RNAs (miRNAs) and circular RNAs (circRNA) is still unclear. Therefore, this study aimed to establish an messenger RNA (mRNA)–miRNA–circRNA competing endogenous RNA (ceRNA) regulatory network to uncover novel molecular signatures using systems biology tools. Six datasets were used to determine differentially expressed genes (DEGs) and miRNAs (DEmiRNA). Accordingly, protein–protein, mRNA–miRNA, and miRNA–circRNA interactions were constructed. Modules were determined and further analyzed in the Drug Gene Budger platform to identify potential therapeutic compounds. We uncovered common 724 DEGs and 278 DEmiRNAs. In the protein–protein interaction network, TMPRSS4, ESR2, TP73, CLEC4E, and TP63 were identified as hub protein coding genes. The mRNA–miRNA interaction network revealed two modules composed of ADRA1A, ADRA1B, hsa-miR-484 and CDH2, TMPRSS4, and hsa-miR-543. The DEmiRNAs in the modules further analyzed to propose potential circRNA regulators in the ceRNA network. These results help deepen the understanding of the mechanisms of IPF. In addition, the molecular leads reported herein might inform future innovations in diagnostics and therapeutics research and development for IPF. [ABSTRACT FROM AUTHOR]

Cancer is a serious and potentially life-threatening disease, which, despite numerous advances over several decades, remains a challenge to treat that challenging to detect at an early stage or treat during the later stages. Long noncoding RNAs are >200 nucleotides long and do not possess protein-coding capacity, instead regulating cellular processes, such as proliferation, differentiation, maturation, apoptosis, metastasis, and sugar metabolism. Several studies have shown the role of lncRNAs and glucose metabolism in regulating several key glycolytic enzymes and the activity of multiple functional signaling pathways during tumor progression. Thus, it is possible to further learn about the effects of lncRNA and glycolytic metabolism on tumor diagnosis, treatment, and prognosis through a thorough investigation of the lncRNA expression profiles and glycolytic metabolism in tumors. This may provide a novel strategy for improving the management of several types of cancer. [ABSTRACT FROM AUTHOR]

Background: Abdominal fat deposition depends on both the proliferation of preadipocytes and their maturation into adipocytes, which is a well-orchestrated multistep process involving many regulatory molecules. Circular RNAs (circRNAs) have emergingly been implicated in mammalian adipogenesis. However, circRNA-mediated regulation in chicken adipogenesis remains unclear. Our previous circRNA sequencing data identified a differentially expressed novel circRNA, 8:27,886,180|27,889,657, during the adipogenic differentiation of chicken abdominal preadipocytes. This study aimed to investigate the regulatory role of circDOCK7 in the proliferation and adipogenic differentiation of chicken abdominal preadipocytes, and explore its molecular mechanisms of competing endogenous RNA underlying chicken adipogenesis. Results: Our results showed that 8:27,886,180|27,889,657 is an exonic circRNA derived from the head-to-tail splicing of exons 19–22 of the dedicator of cytokinesis 7 (DOCK7) gene, abbreviated as circDOCK7. CircDOCK7 is mainly distributed in the cytoplasm of chicken abdominal preadipocytes and is stable because of its RNase R resistance and longer half-life. CircDOCK7 is significantly upregulated in the abdominal fat tissues of fat chickens compared to lean chickens, and its expression gradually increases during the proliferation and adipogenic differentiation of chicken abdominal preadipocytes. Functionally, the gain- and loss-of-function experiments showed that circDOCK7 promoted proliferation, G0/G1- to S-phase progression, and glucose uptake capacity of chicken abdominal preadipocytes, in parallel with adipogenic differentiation characterized by remarkably increased intracellular lipid droplet accumulation and triglyceride and acetyl coenzyme A content in differentiated chicken abdominal preadipocytes. Mechanistically, a pull-down assay and a dual-luciferase reporter assay confirmed that circDOCK7 interacted with gga-miR-301b-3p, which was identified as an inhibitor of chicken abdominal adipogenesis. Moreover, the ACSL1 gene was demonstrated to be a direct target of gga-miR-301b-3p. Chicken ACSL1 protein is localized in the endoplasmic reticulum and mitochondria of chicken abdominal preadipocytes and acts as an adipogenesis accelerator. Rescue experiments showed that circDOCK7 could counteract the inhibitory effects of gga-miR-301b-3p on ACSL1 mRNA abundance as well as the proliferation and adipogenic differentiation of chicken abdominal preadipocytes. Conclusions: CircDOCK7 serves as a miRNA sponge that directly sequesters gga-miR-301b-3p away from the ACSL1 gene, thus augmenting adipogenesis in chickens. These findings may elucidate a new regulatory mechanism underlying abdominal fat deposition in chickens. [ABSTRACT FROM AUTHOR]

Sepsis is a severe medical condition distinguished by immune systematic dysfunction and multiple organic injury, or even failure, resulting from an acute systemic inflammatory response. Acute liver injury (ALI) could be considered as a notable inflammatory outcome of sepsis. Studies have demonstrated the essential roles played by long non-coding RNAs (lncRNAs) in mediating the processes of various diseases, including their ability to engage in interactions with microRNAs (miRNAs) as complexes of competing endogenous RNA (ceRNA) to modulate signaling pathways. In this study, a newly discovered lncRNA, named 220, was identified to function in regulating autophagy and apoptosis in Kupffer cells treated with lipopolysaccharide (LPS). This was achieved through sponging miR-5101 as a ceRNA complex, as identified via high-throughput sequencing. The expression of 220 was found to be significantly different in the hepatic tissues of endotoxemic mice that were treated with LPS for 8 h, ultimately modulating the ALI process. Our studies have collectively demonstrated that 220 is a novel regulator that acts on LPS-induced autophagy and apoptosis in Kupffer cells, thereby mediating the ALI process induced by LPS. Furthermore, the validation of our findings using clinical databases suggests that 220 could potentially serve as a molecular target of clinical, diagnostic, and therapeutic significance in septic liver injury. [ABSTRACT FROM AUTHOR]

Background: Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein. Results: A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells (HRMECs). We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. Additionally, the expression of six lncRNAs and eleven differentially expressed angiogenic genes were validated by qPCR in HRMECs with or without siLGALS1. Several hub genes, such as NRIR, ZFPM2-AS1, LINC0121, apelin, claudin-5, and C-X-C motif chemokine ligand 10, were found to potentially interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response. Conclusions: The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) carries significant morbidity and mortality globally. An increasing number of studies have confirmed that circular RNA (circRNA) is tightly associated with the carcinogenesis and development of GC, especially acting as a competing endogenous RNA for miRNAs. Objective: Our study aimed to construct the circRNA-miRNA-mRNA regulatory network and analyze the function and prognostic significance of the network using bioinformatics tools. Methods: We first downloaded the GC expression profile from the Gene Expression Omnibus database and identified differentially expressed genes and differentially expressed circRNAs. Then, we predicted the miRNA-mRNA interaction pairs and constructed the circRNA-miRNA-mRNA regulatory network. Next, we established a protein-protein interaction network and analyzed the function of these networks. Finally, we primarily validated our results by comparison with The Cancer Genome Atlas cohort and by performing qRT-PCR. Results: We screened the top 15 hub genes and 3 core modules. Functional analysis showed that in the upregulated circRNA network, 15 hub genes were correlated with extracellular matrix organization and interaction. The function of downregulated circRNAs converged on physiological functions, such as protein processing, energy metabolism and gastric acid secretion. We ascertained 3 prognostic and immune infiltration-related genes, COL12A1, COL5A2, and THBS1, and built a nomogram for clinical application. We validated the expression level and diagnostic performance of key prognostic differentially expressed genes. Conclusions: In conclusion, we constructed two circRNA-miRNA-mRNA regulatory networks and identified 3 prognostic and screening biomarkers, COL12A1, COL5A2, and THBS1. The ceRNA network and these genes could play important roles in GC development, diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

• The expression of Sox2ot is increased after peripheral nerve injury. • Overexpression of Sox2ot promotes Schwann cells migration and proliferation. • Sox2ot regulates the expression of Cthrc1 through competitive adsorption of miR-9 in Schwann cells. • Sox2ot provides a new direction for the treatment of peripheral nerve injury. The effects of traditional treatments for peripheral nerve injury (PNI) are not ideal, which has prompted the identification of new therapeutic strategies. As unique glial cells in the peripheral nervous system, Schwann cells (SCs) play an important role in the repair of PNI. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) are involved in the regulation of nerve repair after PNI. In this study, we used microarray technology to detect mRNA and lncRNA expression profiles at different time points after PNI and identified lncRNA Sox2ot-miR-9-Cthrc1 as a competitive endogenous RNA (ceRNA) for further investigation. Expression of lncRNA Sox2ot was increased after PNI, and overexpression of Sox2ot promoted SCs migration and proliferation. Mechanistic analyses confirmed that Sox2ot can regulate the expression of Cthrc1 through competitive adsorption of miR-9 in SCs, ultimately affecting SCs migration and proliferation. Our findings reveal the key role of lncRNA Sox2ot in nerve regeneration and provide a new direction for PNI treatment. [ABSTRACT FROM AUTHOR]

Background/Aim: Recent studies have highlighted the tumor‐suppressive effect of Marsdenia tenacissima extract (MTE) on human cancers. This research unveils the potential impact of MTE on glioma and ascertains the relevant molecular mechanisms. Methods: Glioma cells were treated with MTE, with normal human astrocytes (NHAs) as controls. A battery of function experiments, including the CCK‐8 viability test, colony formation assay, scratch migration assay, and Transwell invasion assay, was executed to address the responses of glioma cells to MTE treatment and gain or loss of function of lncMEG3, miR‐542‐3p, and SFRP1. FISH, RIP, and dual‐luciferase reporter assays were adopted for assessing gene interactions. U251‐GFP‐Luc cells were delivered into nude mice through intracranial injection to develop an orthotopic glioma model for in vivo validation. Results: 200 mg/mL MTE could suppress the proliferating, migrating, and invading properties of glioma cells but not affect those of NHAs. MTE treatment enhanced the expression of lncMEG3, which competes with SFRP1 for binding miR‐542‐3p. SFRP1 could inactivate the Wnt/β‐catenin pathway. Animal experimentation substantiated the antitumor activity and mechanism of MTE in nude mice. Conclusions: MTE suppresses glioma via the lncMEG3/miR‐542‐3p/SFRP1/Wnt/β‐catenin axis. These findings contribute to a theoretical basis for the use of MTE for glioma patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Non-small lung cancer ranks first in the cancer-related death of all malignant tumors. Exploring novel biological targets is of great significance for diagnosis and therapy of NSCLC. OBJECTIVE: In this study, we aimed to explore the effect of LINC00668 on the biological functions of NSCLC cells and the underlying mechanism. METHODS: RT-qPCR assays and western blot assays were utilized to estimate the relative gene expression at mRNA and protein levels, respectively. CCK8, colony formation, wound healing, transwell, and cell apoptosis assays were employed to assess cell function. IHC and FISH assays were used to determine the gene expression in NSCLC tissues. RIP and dual-luciferase assays were conducted to validate the combination between LINC00668 and miR-518c-3p. The correlation of expression between miR-518c-3p and LINC00668 or TRIP4 was determined by Pearson correlation analysis. RESULTS: LINC00668 was aberrantly upregulated in NSCLC tumor tissues and cell lines. Inhibition of LINC00668 significantly suppressed tumor proliferation, migration, invasion and promoted cell apoptosis. Mechanistically, LINC00668 could bind to miR-518c-3p, thus targeting the 3'UTR of TRIP4. TRIP4 overexpression rescued the weakened cell function mediated by LINC00668 silencing. CONCLUSIONS: LINC00668 acted as an oncogene in NSCLC progression through miR-518c-3p/TRIP4 axis. Our study disclosed a new mechanism of LINC00668 functioned in NSCLC and may give a deeper insight of the targeted therapy of NSCLC in the future. [ABSTRACT FROM AUTHOR]

China has a long history of pig breeding and a number of local breeds. The Songliao Black pig, bred in China in 2009, shows high variation in backfat thickness and therefore is well‐suited to fat deposition research. Fat deposition is a complex trait, and the underlying regulatory factors are not fully characterized. In this study, the molecular basis of fat deposition traits was evaluated by comparisons between three individuals with extremely high‐backfat thickness and three with extremely low‐backfat thickness selected from 53 gilts. Subcutaneous adipose tissues of the back were collected for strand‐specific library RNA sequencing (RNA‐seq) and small RNA‐seq. We identified 13 184 mRNAs, 2046 long non‐coding (lnc)RNAs, and 494 micro (mi)RNAs by high‐throughput sequencing. Furthermore, we detected 150 differentially expressed mRNAs, 66 differentially expressed lncRNAs, and eight differentially expressed miRNAs. A functional enrichment analysis indicated that these genes are involved in multiple fat metabolism‐related pathways, including positive regulation of fat cell differentiation, and fat digestion and absorption. We used various algorithms (miRanda, TargetScan, and RNAhybrid) to predict targeting relationships and constructed a competing endogenous RNA network containing seven lncRNAs, three miRNAs, and six mRNAs. All these genes were differentially expressed between the extremely high and low backfat thickness groups or enriched in pathways related to fat metabolism. Our results provide insight into the regulatory mechanisms by which non‐coding RNAs and their target genes influence backfat deposition in pigs. Furthermore, our newly constructed competing endogenous RNA (lncRNA‐miRNA‐mRNA) network provides a basis for further exploration of fat deposition traits and non‐coding RNA functions. [ABSTRACT FROM AUTHOR]

Background: Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role in HCC progression. However, the underlying mechanisms remain unclear. Methods: Differentially expressed immune-related genes were obtained from the Immport, GEO, and TCGA databases. The mRNA and protein expression levels in HCC tissues and adjacent normal tissues were confirmed, and we further investigated the methylation levels of these biomarkers to explore their function. Then, the TIMER and TISCH databases were used to assess the relationship between immune infiltration and hub genes. Survival analysis and univariate and multivariate Cox models were used to evaluate the association between hub genes and HCC diagnosis. Hub gene expression was experimentally validated in six HCC cell lines and 15 HCC samples using qRT-PCR and immunohistochemistry. The hub genes were uploaded to DSigDB for drug prediction enrichment analysis. Results: We identified that patients with abnormal miRNAs (hsa-miR-125b-5p and hsa-miR-21-5p) and their targeted genes (NTF3, PSMD14, CD320, and SORT1) had a worse prognosis. Methylation analysis of miRNA-targeted genes suggested that alteration of methylation levels is also a factor in the induction of tumorigenesis. We also found that the development of HCC progression caused by miRNA-mRNA interactions may be closely correlated with the infiltration of immunocytes. Moreover, the GSEA, GO, and KEGG analysis suggested that several common immune-related biological processes and pathways were related to miRNA-targeted genes. The results of qRT-PCR, immunohistochemistry, and western blotting were consistent with our bioinformatics results, suggesting that abnormal miRNAs and their targeted genes may affect HCC progression. Conclusions: Briefly, our study systematically describes the mechanisms of miRNA-mRNA interactions in HCC and predicts promising biomarkers that are associated with immune filtration for HCC progression. [ABSTRACT FROM AUTHOR]

Nucleolar and spindle-associated protein 1 (NUSAP1) is a potential molecular marker and intervention target for glioblastoma (GBM). In this study, we aim to investigate upstream regulatory lncRNAs and miRNAs of NUSAP1 through both experimental and bioinformatic methods. We screened upstream lncRNAs and miRNAs of NUSAP1 through multiple databases based on ceRNA theory. Then, in vitro and in vivo experiments were performed to elucidate the relevant biological significance and regulatory mechanism among them. Finally, the potential downstream mechanism was discussed. LINC01393 and miR-128-3p were screened as upstream regulatory molecules of NUSAP1 by TCGA and ENCORI databases. The negative correlations among them were confirmed in clinical specimens. Biochemical studies revealed that overexpression or knockdown of LINC01393 respectively enhanced or inhibited malignant phenotype of GBM cells. MiR-128-3p inhibitor reversed LINC01393 knockdown-mediated impacts on GBM cells. Then, dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to validate LINC01393/miR-128-3p/NUSAP1 interactions. In vivo, LINC01393-knockdown decreased tumor growth and improved mice survival, while restoration of NUSAP1 partially reversed these effects. Additionally, enrichment analysis and western blot revealed that the roles of LINC01393 and NUSAP1 in GBM progression were associated with NF-κB activation. Our findings showed that LINC01393 sponged miR-128-3p to upregulate NUSAP1, thereby promoting GBM development and progression via activating NF-κB pathway. This work deepens understanding of GBM mechanisms and provides potential novel therapeutic targets for GBM. [ABSTRACT FROM AUTHOR]

Background: Stroke attributable to atrial fibrillation (AF related stroke, AFST) accounts for 13 ~ 26% of ischemic stroke. It has been found that AFST patients have a higher risk of disability and mortality than those without AF. Additionally, it's still a great challenge to treat AFST patients because its exact mechanism at the molecular level remains unclear. Thus, it's vital to investigate the mechanism of AFST and search for molecular targets of treatment. Long non-coding RNAs (lncRNAs) are related to the pathogenesis of various diseases. However, the role of lncRNAs in AFST remains unclear. In this study, AFST-related lncRNAs are explored using competing endogenous RNA (ceRNA) network analysis and weighted gene co-expression network analysis (WGCNA). Methods: GSE66724 and GSE58294 datasets were downloaded from GEO database. After data preprocessing and probe reannotation, differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) between AFST and AF samples were explored. Then, functional enrichment analysis and protein-protein interaction (PPI) network analysis of the DEMs were performed. At the meantime, ceRNA network analysis and WGCNA were performed to identify hub lncRNAs. The hub lncRNAs identified both by ceRNA network analysis and WGCNA were further validated by Comparative Toxicogenomics Database (CTD). Results: In all, 19 DELs and 317 DEMs were identified between the AFST and AF samples. Functional enrichment analysis suggested that the DEMs associated with AFST were mainly enriched in the activation of the immune response. Two lncRNAs which overlapped between the three lncRNAs identified by the ceRNA network analysis and the 28 lncRNAs identified by the WGCNA were screened as hub lncRNAs for further validation. Finally, lncRNA GAS6-AS1 turned out to be associated with AFST by CTD validation. Conclusion: These findings suggested that low expression of GAS6-AS1 might exert an essential role in AFST through downregulating its downstream target mRNAs GOLGA8A and BACH2, and GAS6-AS1 might be a potential target for AFST therapy. [ABSTRACT FROM AUTHOR]

Background: Our previous studies have confirmed that miR-154-5p can regulate pRb expression, and thus, play a tumor suppressor role in HPV16 E7-induced cervical cancer. However, its upstream molecules have not been elucidated in the progression of cervical cancer. This study aimed to explore the role of the miR-154-5p upstream molecule, hsa_circ_0000276 in cervical cancer development and its possible mechanisms of action. Methods: We detected differences in whole transcriptome expression profiles of cervical squamous carcinoma and tissues adjacent to cervical cancer tissues from patients using microarray technology to predict circular RNAs (circRNAs) with binding sites to miR-154-5p. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of hsa_circ_0000276 (which had the strongest binding capacity to miR-154 and was selected as the target molecule) in cervical cancer tissues, followed by in vitro functional assays. Downstream microRNAs (miRNAs) and mRNAs of hsa_circ_0000276 were identified using transcriptome microarray data and databases, while the protein–protein interaction networks were obtained using STRING. A competing endogenous RNA (ceRNA) network centered on hsa_circ_0000276 was constructed using Cytoscape and GO and KEGG databases. Abnormal expression and prognosis of critical downstream molecules were analyzed using gene databases and molecular experiments. qRT-PCR and western blot analysis was performed to verify the expression of candidate genes. Results: We identified 4,001 differentially expressed circRNAs between HPV16-positive cervical squamous carcinoma and benign cervical tissues and 760 circRNAs targeting miR-154-5p, including hsa_circ_0000276. hsa_circ_0000276 and miR-154-5p directly bound, and hsa_circ_0000276 was upregulated, in cervical precancerous lesions and cervical cancer tissues and cells. Silencing hsa_circ_0000276 inhibited G1/S transition and cell proliferation and promoted apoptosis in SiHa and CaSki cells. Bioinformatics analysis showed that the hsa_circ_0000276 ceRNA network included 17 miRNAs and seven mRNAs, and downstream molecules of hsa_circ_0000276 were upregulated in cervical cancer tissues. These downstream molecules were associated with a poor prognosis and affected cervical cancer-associated immune infiltration. Of these, expression of CD47, LDHA, PDIA3, and SLC16A1 was downregulated in sh_hsa_circ_0000276 cells. Conclusions: Our findings show that hsa_circ_0000276 exerts cancer-promoting effects in cervical cancer and is an underlying biomarker for cervical squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Obesity is a major risk factor for cardiovascular, cerebrovascular, metabolic, and respiratory diseases, and it has become an important social health problem affecting the health of the population. Obesity is affected by both genetic and environmental factors. In this study, we constructed a diet-induced obese C57BL/6J mouse model and performed deep RNA sequencing (RNA-seq) on liner-depleted RNA extracted from the liver tissues of the mice to explore the underlying mechanisms of obesity. A total of 7469 circular RNAs (circRNAs) were detected, and 21 were differentially expressed (DE) in the high-fat diet (HFD) and low-fat diet (LFD) groups. We then constructed a comprehensive circRNA-associated competing endogenous RNA (ceRNA) network. Bioinformatic analysis indicated that DE circRNAs associated with lipid metabolic-related pathways may act as miRNA sponges to modulate target gene expression. CircRNA1709 and circRNA4842 may serve as new candidates to regulate the expression of PTEN. This study provides systematic circRNA-associated ceRNA profiling in HFD mouse liver, and the results can aid early diagnosis and the selection of treatment targets for obesity in the future. [ABSTRACT FROM AUTHOR]

Valgus-valgus deformity (VVD) is a common leg deformity in broilers with inward or outward deviation of the tibiotarsus and tarsometatarsus. The competing endogenous RNA (ceRNA) network plays an essential role in the study of leg disease. However, its role in the etiology and pathogenesis of VVD remains unclear. Here, based on case (VVD) and control (normal) group design, we performed analyses of differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed mRNAs (DEmRNAs). Transcriptome data derived 86 DEcircRNAs, 13 DEmiRNAs and 410 DEmRNAs. Functional analysis showed that DEmRNAs were significantly enriched in cell cycle, apoptosis, ECM-receptor interaction, FoxO signaling pathway and protein processing synthesis. DEcirc/miRNA-associated DEmRNAs were associated with skeletal and muscle growth and development pathways, including mTOR, Wnt, and VEGF signaling pathways. Subsequently, a circRNA–miRNA–mRNA regulatory network was constructed based on the ceRNA hypothesis, including 8 circRNAs, 6 miRNAs, and 31 mRNAs, which were significantly enriched in the skeletal developmental pathway. Finally, two key mRNAs (CDC20 and CTNNB1) and their regulatory axes were screened by the PPI network and cytohubba. The expression levels of CDC20 and CTNNB1 in cartilage and seven other tissues were also quantified by qPCR. In conclusion, we analyzed the functions of DEmRNA, DEcircRNA and DEmiRNA and constructed the hub ceRNA regulatory axis, and obtained two hub genes, CDC20 and CTNNB1. The study more deeply explored the etiology and pathogenesis of VVD and lays the foundation for further study of the role of the ceRNA network on skeletal development. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteoarthritis is one of the most common joint diseases and the leading cause of chronic joint pain and limited mobility in older adults. As an emerging important member of the competing endogenous RNA regulatory network, circular RNA plays an important role in the occurrence and development of osteoarthritis. OBJECTIVE: To overview circular RNAs, their biological functions, and competing endogenous RNAs and to emphatically review the research progress in the role of circular RNAs as competing endogenous RNAs in osteoarthritis. METHODS: CNKI, WanFang, VIP Chinese journal database, and PubMed databases were searched for relevant articles using “osteoarthritis, circular RNA, competing endogenous RNA” as Chinese and English search terms. We excluded outdated and repeated views, sorted out the retrieved literature, and selected 64 articles for review. RESULTS AND CONCLUSION: The mechanism of circular RNAs by which affect the occurrence of osteoarthritis is mainly to bind microRNAs as competing endogenous RNAs, thereby regulating the expression level of their target genes and regulating the related proliferation, apoptosis and differentiation of the cells to which they belong. Circular RNA as a competing endogenous RNA participates in regulating the proliferation, apoptosis, and autophagy of chondrocytes. Circular RNA as a competing endogenous RNA participates in regulating the formation and degradation of the extracellular matrix of chondrocytes. Circular RNA as a competing endogenous RNA is involved in regulating the production of inflammatory factors in chondrocytes. Circular RNA as a competing endogenous RNA is involved in regulating synovial cell apoptosis and autoimmune responses. Since circular RNAs are highly stable and conserved, the research on the competing endogenous RNA regulatory network mediated by circular RNAs will also open up new avenues for basic research on osteoarthritis, which help understand the pathogenesis of osteoarthritis more comprehensively. Circular RNA is also expected to be a high-quality early diagnostic marker and therapeutic target for osteoarthritis. To date, the competing endogenous RNA regulatory network is still in the verification stage. With the rapid development of bioinformatics, the competing endogenous RNA regulatory network needs to be further improved and supplemented. [ABSTRACT FROM AUTHOR]

Objective: Osteoporosis is a progressive systemic skeletal disorder. Multiple profiling studies have contributed to characterizing biomarkers and therapeutic targets for osteoporosis. However, due to the limitation of the platform of miRNA sequencing, only a part of miRNA can be sequenced based on one platform. Materials and methods: In this study, we performed miRNA sequencing in osteoporosis bone samples based on a novel platform Illumina Hiseq 2500. Bioinformatics analysis was performed to construct osteoporosis-related competing endogenous RNA (ceRNA) networks. Gene interference and osteogenic induction were used to examine the effect of identified ceRNA networks on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs). Results: miR-1303 was lowly expressed, while cochlin (COCH) and KCNMA1-AS1 were highly expressed in the osteoporosis subjects. COCH knockdown improved the osteogenic differentiation of HBMSCs. Meanwhile, COCH inhibition compensated for the suppression of osteogenic differentiation of HBMSCs by miR-1303 knockdown. Further, KCNMA1-AS1 knockdown promoted osteogenic differentiation of HBMSCs through downregulating COCH by sponging miR-1303. Conclusions: Our findings suggest that the KCNMA1-AS1/miR-1303/COCH axis is a promising biomarker and therapeutic target for osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: Steroid-induced osteonecrosis of the femoral head (SONFH) was a refractory orthopedic hip joint disease in the young and middle-aged people, but the pathogenesis of SONFH remained unclear. We aimed to identify the potential genes and screen potential therapeutic compounds for SONFH. Methods: The microarray was obtained for blood tissue from the GEO database, and then it identifies differentially expressed genes (DEGs). The DEGs were analyzed to obtain the differences in immune cell infiltration. The gene functional enrichment analysis of SONFH was analyzed. The PPI of DEGs was identified through the STRING database, and the cluster modules and hub genes were ascertained using MCODE and CytoHubba, and the ROC curve of hub genes was analyzed, and the tissues distribution of hub genes was understood by the HPA, Bgee and BioGPS databases. The hub genes and target miRNAs and corresponding upstream lncRNAs were predicted by TargetScan, miRDB and ENCORI database. Subsequently, we used CMap, DGIdb and L1000FWD databases to identify several potential therapeutic molecular compounds for SONFH. Finally, the AutoDockTools Vina, PyMOL and Discovery Studio were employed for molecular docking analyses between compounds and hub genes. Results: The microarray dataset GSE123568 was obtained related to SONFH. There were 372 DEGs including 197 upregulated genes and 175 downregulated genes by adjusted P value < 0.01 and |log2FC|> 1. Several significant GSEA enrichment analysis and biological processes and KEGG pathway associated with SONFH were identified, which were significantly related to cytoskeleton organization, nucleobase-containing compound catabolic process, NOD-like receptor signaling pathway, MAPK signaling pathway, FoxO signaling pathway, neutrophil-mediated immunity, neutrophil degranulation and neutrophil activation involved in immune response. Activated T cells CD4 memory, B cells naïve, B cells memory, T cells CD8 and T cells gamma delta might be involved in the occurrence and development of SONFH. Three cluster modules were identified in the PPI network, and eleven hub genes including FPR2, LILRB2, MNDA, CCR1, IRF8, TYROBP, TLR1, HCK, TLR8, TLR2 and CCR2 were identified by Cytohubba, which were differed in bone marrow, adipose tissue and blood, and which had good diagnostic performance in SONFH. We identified IRF8 and 10 target miRNAs that was utilized including Targetsan, miRDB and ENCORI databases and 8 corresponding upstream lncRNAs that was revealed by ENCORI database. IRF8 was detected with consistent expression by qRT-PCR. Based on the CMap, DGIdb and L1000FWD databases, the 11 small molecular compounds that were most strongly therapeutic correlated with SONFH were estradiol, genistein, domperidone, lovastatin, myricetin, fenbufen, rosiglitazone, sirolimus, phenformin, vorinostat and vinblastine. All of 11 small molecules had good binding affinity with the IRF8 in molecular docking. Conclusion: The occurrence of SONFH was associated with a "multi-target" and "multi-pathway" pattern, especially related to immunity, and IRF8 and its noncoding RNA were closely related to the development of SONFH. The CMap, DGIdb and L1000FWD databases could be effectively used in a systematic manner to predict potential drugs for the prevention and treatment of SONFH. However, additional clinical and experimental research is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Gefitinib resistance limits the therapeutic efficacy of gefitinib to lung adenocarcinoma (LUAD). The goal of this research is to learn more about the lncRNA AFAP1-AS1 and how it functions in gefitinib-resistant LUAD cells. Methods: RT-qPCR was performed to test the expression of AFAP1-AS1, miR-653-5p and AGR2 in LUAD tissues with acquired resistance to gefitinib or not as well as in gefitinib-resistant LUAD cells. Cell proliferation, invasion and apoptosis were measured by CCK8 assays, transwell invasion assays and flow cytometry, respectively. Luciferase reporter assay showed that miR-653-5p and AFAP1-AS1 or AGR2 interactions. Results: In gefitinib-resistant LUAD cells and tissues, AFAP1-AS1 was overexpressed. Meanwhile, silencing AFAP1-AS1 reduced proliferation and migration while increasing apoptosis and gefitinib sensitivity. Mechanically, AFAP1-AS1 sequestered the miR-653-5p and blocked the inhibition of miR-653-5p to AGR2 and stepwise upregulated AGR2 overexpression in LUAD gefitinib resistant cells, resulting gefitinib resistance in LUAD. Conclusion: AFAP1-AS1 promotes gefitinib-resistance LUAD cells through a previously unrecognized miR-653-5p/AGR2 axis, suggesting targeting AFAP1-AS1/miR-653-5p/AGR2 axis might be a promising way for LUAD intervention. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a type of malignant tumor. miRNAs are noncoding RNAs and their differential expression patterns are observed in HCC-induced by alcoholism, HBV and HCV infections. By acting as a competing endogenous RNA (ceRNA), circRNA regulates the miRNA function, indirectly controlling the gene expression and leading to HCC progression. In the present study, data mining was performed to screen out all miRNAs and circRNA involved in alcohol, HBV or HCV-induced HCC with statistically significant (≤0.05%) expression levels reported in various studies. Further, the interaction of miRNAs and circRNA was also investigated to explore their role in HCC due to various causative agents. Together, these study data provide a deeper understanding of the circRNA–miRNA regulatory mechanisms in HCC. These screened circRNA, miRNA and their interactions can be used as prognostic biomarkers or therapeutic targets for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Background: Among the most lethal cancers, pancreatic adenocarcinoma (PAAD) is an essential component of digestive system malignancies that still lacks effective diagnosis and treatment methods. As exosomes and competing endogenous RNA (ceRNA) regulatory networks in tumors go deeper, we expect to construct a ceRNA regulatory network derived from blood exosomes of PAAD patients by bioinformatics methods and develop a survival prediction model based on it. Methods: Blood exosome sequencing data of PAAD patients and normal controls were downloaded from the exoRbase database, and the expression profiles of exosomal mRNA, lncRNA, and circRNA were differentially analyzed by R. The related mRNA, circRNA, lncRNA, and their corresponding miRNA prediction data were imported into Cytoscape software to visualize the ceRNA network. Then, we conducted GO and KEGG enrichment analysis of mRNA in the ceRNA network. Genes that express differently in pancreatic cancer tissues compared with normal tissues and associate with survival (P < 0.05) were determined as Hub genes by GEPIA. We identified optimal prognosis-related differentially expressed mRNAs (DEmRNAs) and generated a risk score model by performing univariate and multivariate Cox regression analyses. Results: 205 DEmRNAs, 118 differentially expressed lncRNAs (DElncRNAs), and 98 differentially expressed circRNAs (DEcircRNAs) were screened out. We constructed the ceRNA network, and a total of 26 mRNA nodes, 7 lncRNA nodes, 6 circRNA nodes, and 16 miRNA nodes were identified. KEGG enrichment analysis showed that the DEmRNAs in the regulatory network were mainly enriched in Human papillomavirus infection, PI3K-Akt signaling pathway, Osteoclast differentiation, and ECM-receptor interaction. Next, six hub genes (S100A14, KRT8, KRT19, MAL2, MYO5B, PSCA) were determined through GEPIA. They all showed significantly increased expression in cancer tissues compared with control groups, and their high expression pointed to adverse survival. Two optimal prognostic-related DEmRNAs, MYO5B (HR = 1.41, P < 0.05) and PSCA (HR = 1.10, P < 0.05) were included to construct the survival prediction model. Conclusion: In this study, we successfully constructed a ceRNA regulatory network in blood exosomes from PAAD patients and developed a two-gene survival prediction model that provided new targets which shall aid in diagnosing and treating PAAD. [ABSTRACT FROM AUTHOR]

Simple Summary: MEG3 is a class of lncRNA, which is considered a tumor suppressor. It is lost or decreased in different biological processes of various human tumors and is closely related to various diseases. MEG3 can modulate the expression of target genes through transcription, translation, post-translational modification and epigenetic regulation. Studies have shown that MEG3 dysfunction has been linked to a poor prognosis and drug resistance. MEG3 mediates the hallmarks of cancer through a variety of mechanisms, acting as a tumor suppressor to limit tumor growth. Hence, MEG3 is a potential prognostic marker and antitumor therapeutic target. Long non-coding RNAs (lncRNAs) are critical regulators in various biological processes involved in the hallmarks of cancer. Maternally expressed gene 3 (MEG3) is lncRNA that regulates target genes through transcription, translation, post-translational modification, and epigenetic regulation. MEG3 has been known as a tumor suppressor, and its downregulation could be found in various cancers. Furthermore, clinical studies revealed that impaired MEG3 expression is associated with poor prognosis and drug resistance. MEG3 exerts its tumor suppressive effect by suppressing various cancer hallmarks and preventing cells from acquiring cancer-specific characteristics; as it could suppress tumor cells proliferation, invasion, metastasis, and angiogenesis; it also could promote tumor cell death and regulate tumor cell metabolic reprogramming. Hence, MEG3 is a potential prognostic marker, and overexpressing MEG3 might become a potential antitumor therapeutic strategy. Herein, we summarize recent knowledge regarding the role of MEG3 in regulating tumor hallmarks as well as the underlying molecular mechanisms. Furthermore, we also discuss the clinical importance of MEG3, as well as their potential in tumor prognosis and antitumor therapeutic strategies. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNA) can regulate mammary gland development and lactation physiological activities. However, the molecular genetic mechanisms of lncRNA in mammary gland involution and cell remodeling remain unclear. This work analyzed the expression characteristics and molecular functions of lncRNA in goat mammary gland tissue at the late lactation (LL), dry period (DP), and late gestation (LG) stages. Sequencing results showed that 3074 lncRNAs were identified in non-lactating goat mammary gland tissue. Statistical analysis of lncRNA length characteristics and exon number found that goat lncRNAs were shorter in length, had fewer exons, and significantly lower expression levels than those of protein-coding genes. 331 differentially expressed lncRNAs were identified in the three comparison groups (LLvsDP, DPvsLG, and LLvsLG), which indicated that the lncRNAs expression at the transcriptional level were changed during mammary involution. Interestingly, lncRNAs were more actively expressed during the dry period compared to lactation, suggesting that lncRNAs in mammary glands are developmentally specific. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that lncRNAs could regulate immune function, cell proliferation, apoptosis, hormones, substance metabolism, transport, and intercellular communication in the mammary gland through various action modes. Among them, cis-acting lncRNAs enhanced the protection of mammary gland health during the dry period and late gestation. The above reflects the particular mechanisms of lncRNA to adapt to the developmental needs of mammary involution and remodeling. Furthermore, in the lncRNA-miRNA-mRNA network associated with mammary gland development, the expression of LOC102168552 was higher in late gestation than in the dry period and late lactation. Its expression was positively correlated with PRLR and negatively correlated with chi-miR-324-3p. Overexpression of LOC102168552 in goat mammary epithelial cells cultured in vitro could up-regulate PRLR to activate the prolactin signaling pathway by competitively binding to chi-miR-324-3p, promoting cell proliferation, reducing cell cycle arrest in the G1 / S phase, and inhibiting apoptosis. However, overexpression of LOC102168552 alone did not affect mammary cell growth status and the prolactin signaling pathway. This indicates that LOC102168552 must rely on chi-miR-324-3p to inhibit mammary cell apoptosis. In conclusion, the above analysis revealed that lncRNAs in goat mammary tissue are differentially expressed at different stages of involution. As expected, lncRNAs adaptively regulate various physiological activities during mammary gland involution through multiple modes of action, in preparation for a new round of lactation. These findings provide a reference and help further understand the regulatory role of lncRNAs in mammary cell involution and remodeling. • Characterization of lncRNAs in non-lactating mammary tissue of dairy goats. • The expression of lncRNA changes during mammary gland involution. • LncRNAs regulate multiple physiological activities to adapt to the mammary gland involution through various action modes. • Overexpression of LOC102168552 promotes the growth of mammary epithelial cells by competitively binding to chi-miR-324-3p. [ABSTRACT FROM AUTHOR]

Background: Centrosomal protein 55 (CEP55) is implicated in the tumorigenesis of bladder cancer (BC) but the detailed molecular mechanisms are unknown. We aim to develop a potential competing endogenous RNA (ceRNA) network related with CEP55 in BC. Methods: We first extracted the expression profiles of RNAs from The Cancer Genome Atlas (TCGA) database and used bioinformatic analysis to establish ceRNAs in BC. Real-time quantity PCR (RT-qPCR) and immunohistochemical analysis were performed to measure CEP55 expression in different bladder cell lines and different grades of cancer. Bioinformatics analysis and luciferase assays were conducted to predict potential binding sites among miR-497-5p, CEP55, parathyroid hormone like hormone (PTHLH) and high mobility group A2 (HMGA2). Tumor xenograft model was used to show the effect of CEP55 3'-UTR on cisplatin therapy. Bioinformatics analysis, luciferase assays, and 5' rapid amplification of cDNA ends (5'RACE) were to explore the function of CEP55 3'-untranslated region (3'-UTR) on targeting miR-497-5p. Western blot and immunofluorescence assays were to detect the epithelial–mesenchymal transition (EMT) induction of CEP55 3'-UTR. Results: CEP55 expression as well as the expression levels of the oncogenic proteins PTHLH and HMGA2 were upregulated in BC cells while miR-497-5p was downregulated. Low miR-497-5p expression and high CEP55 and HMGA2 expression levels were associated with more advanced tumor clinical stage and pathological grade. Overexpression of the CEP55 3'-UTR promoted the proliferation, migration, and invasion of the EJ cell line in vitro and accelerated EJ-derived tumor growth in nude mice, while inhibition of the CEP55 3'-UTR suppressed all of these oncogenic processes. In addition, CEP55 3'-UTR upregulation reduced the cisplatin sensitivity of BC cell lines and xenograft tumors. Bioinformatics analysis, luciferase assays, and 5'RACE suggested that the CEP55 3'-UTR functions as a ceRNA targeting miR-497-5p, leading to miR-497-5p downregulation and disinhibition of PTHLH and HMGA2 expression. Further, CEP55 downregulated miR-497-5p transcription by promoting NF- κ B signaling. In turn, CEP55 3'-UTR ultimately promotes EMT and tumorigenesis by activating P38MAPK and ERK 1/2 pathways. Conclusions: These results suggest that a ceRNA regulatory network involving CEP55 upregulates PTHLH and HMGA2 expression by suppressing endogenous miR-497-5p. We unveiled a novel mechanism of BC metastasis, and could become novel therapeutics targets in BC. [ABSTRACT FROM AUTHOR]

In recent years, circularRNA (circRNA) mediated endogenous competitive RNA (ceRNA) regulatory network has been proved to play a key role in pathological and physiological processes following acute ischemic stroke (AIS) injury. Moreover, circRNA is expected to be a biomarker of AIS after the wide application of molecular diagnostic tools. The summary of the above studies can broaden the vision of the pathogenesis of AIS and provide new ideas for its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Study Question: Would the construction of a competing endogenous RNA (ceRNA) network help identify new drug targets for the development of potential therapies for polycystic ovary syndrome (PCOS)?Summary Answer: Both Food and Drug Administartion (FDA)-approved and candidate drugs could be identified by combining bioinformatics approaches with clinical sample analysis based on our established ceRNA network.What Is Known Already: Thus far, no effective drugs are available for treating PCOS. ceRNAs play crucial roles in multiple diseases, and some of them are in current use as prognostic biomarkers as well as for chemo-response and drug prediction.Study Design, Size, Duration: For the bioinformatics part, five microarrays of human granulosa cells were considered eligible after applying strict screening criteria and were used to construct the ceRNA network for target identification. For population-based validation, samples from 24 women with and without PCOS were collected from January 2021 to July 2021.Participants/materials, Setting, Methods: The public data included 27 unaffected women and 25 women with PCOS, according to the Rotterdam criteria proposed in 2003. The limma and RobustRankAggreg R packages were used to identify differentially expressed messenger RNAs and noncoding RNAs. Gene Ontology, Reactome and Kyoto Encyclopedia of Genes and Gemomes (KEGG) enrichment analyses were performed. A ceRNA network was constructed by integrating the differentially expressed genes and target genes. The population-based validation included human luteinized granulosa cell samples from 12 unaffected women and 12 women with PCOS. Quantitative real-time polymerase chain reaction was conducted to detect the levels of mRNAs and microRNAs (miRNAs). Connectivity map and computational model algorithms were implemented to predict therapeutic drugs from the ceRNA network. Additionally, we compared the predicted drugs with known clinical medications in DrugBank.Main Results and the Role Of Chance: A set of 10 mRNAs, 11 miRNAs and 53 long non-coding RNAs (lncRNAs) were differentially expressed. Functional enrichment analysis revealed the highest relevance to immune system-related biological processes and signalling pathways, such as cytokine secretion and leucocyte chemotaxis. A ceRNA consisting of two lncRNAs, two miRNAs and five mRNAs was constructed. Through network construction via bioinformatic analysis, we identified some already approved drugs (such as metformin) that could target some molecules in the network as potential drug candidates for PCOS.Large Scale Data: Public sequencing data were obtained from GSE34526, GSE84376, GSE102293, GSE106724 and GSE114419, which have been deposited in the Gene Expression Omnibus database.Limitations, Reasons For Caution: Experiments, such as immunoprecipitation, luciferase reporter assays and animal model studies, are needed to validate the potential targets in the ceRNA network before the identified drug candidates can be tested using cellular and animal model systems.Wider Implications Of the Findings: Our findings provide new bioinformatic insight into the possible pathogenesis of PCOS from ceRNA network analysis, which has not been previously studied in the human reproductive field. Our study also reveals some potential drug candidates for the future development of possible therapies against PCOS.Study Funding/competing Interest(s): This study was supported by grants from the National Key Research and Development Program of China (2021YFC2700400) and the National Natural Science Foundation of China (82001498). The authors have no conflicts of interest to disclose. [ABSTRACT FROM AUTHOR]

With the rapid increase in the incidence of diabetes, non-healing diabetic wounds have posed a huge challenge to public health. Endothelial progenitor cell (EPC) has been widely reported to promote wound repairing, while its number and function were suppressed in diabetes. However, the specific mechanisms and competing endogenous RNA (ceRNA) network of EPCs in diabetes remain largely unknown. Thus, the transcriptome analyses were carried in the present study to clarify the mechanism underlying EPCs dysfunction in diabetes. EPCs were successfully isolated from rats. Compared to the control, diabetic rat-derived EPCs displayed impaired proliferation, migration, and tube formation ability. The differentially expressed (DE) RNAs were successfully identified by RNA sequencing in the control and diabetic groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DE mRNAs were significantly enriched in terms and pathways involved in the functions of EPCs and wound healing. Protein–protein interaction networks revealed critical DE mRNAs in the above groups. Moreover, the whole lncRNA–miRNA–mRNA ceRNA network was constructed, in which 9 lncRNAs, 9 mRNAs, and 5 miRNAs were further validated by quantitative real-time polymerase chain reaction. Rno-miR-10b-5p and Tgfb2 were identified as key regulators of EPCs dysfunction in diabetes. The present research provided novel insight into the underlying mechanism of EPCs dysfunction in diabetes and prompted potential targets to restore the impaired functions, thus accelerating diabetic wound healing. Key messages: • Compared to the control, diabetic rat-derived EPCs displayed impaired proliferation, migration, and tube formation ability. • The DE RNAs were successfully identified by RNA sequencing in the control and diabetic groups and analyzed by DE, GO, and KEGG analysis. • PPI and lncRNA–miRNA–mRNA ceRNA networks were constructed. • 9 lncRNAs, 9 mRNAs, and 5 miRNAs were further validated by qRT-PCR. • Rno-miR-10b-5p and Tgfb2 were identified as key regulators of EPCs dysfunction in diabetes. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer (CC) is a common cancer in female, which is associated with problems like poor prognosis. Circular RNA (circRNA) is a kind of competing endogenous RNA (ceRNA) that has an important role in regulating microRNA (miRNA) in many cancers. The regulatory mechanisms of CC immune microenvironment and the transcriptome level remain to be fully explored. Methods: In this study, we constructed the ceRNA network through the interaction data and expression matrix of circRNA, miRNA and mRNA. Meanwhile, based on the gene expression matrix, CIBERSORT algorithm was used to reveal contents of tumor-infiltrating immune cells (TIICs). Then, we screened prognostic markers based on ceRNA network and immune infiltration and constructed two nomograms. In order to find immunological differences between the high- and low-risk CC samples, we examined multiple immune checkpoints and predicted the effect of PD-L1 ICI immunotherapy. In addition, the sensitive therapeutics for high-risk patients were screened, and the potential agents with anti-CC activity were predicted by Connective Map (CMap). Results: We mapped a ceRNA network including 5 circRNAs, 17 miRNAs and 129 mRNAs. From the mRNA nodes of the network six genes and two kind of cells were identified as prognostic makers for CC. Among them, there was a significant positive correlation between CD8+ T cells and SNX10 gene. The results of TIDE and single sample GSEA (ssGSEA) showed that T cells CD8 do play a key role in inhibiting tumor progression. Further, our study screened 24 drugs that were more sensitive to high-risk CC patients and several potential therapeutic agents for reference. Conclusions: Our study identified several circRNA-miRNA-mRNA regulatory axes and six prognostic genes based on the ceRNA network. In addition, through TIIC, survival analysis and a series of immunological analyses, T cells were proved to be good prognostic markers, besides play an important role in the immune process. Finally, we screened 24 potentially more effective drugs and multiple potential drug compounds for high- and low-risk patients. [ABSTRACT FROM AUTHOR]