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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]

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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]

Abstract 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 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 Purpose Multiple myeloma (MM) is the second most common hematologic malignancy, and there is no cure for this disease. This study aimed to explore the prognostic value of long noncoding RNAs (lncRNAs) in MM and to reveal related immune and chemotherapy resistance mechanisms. Methods In this study, lncRNA profiles from the Multiple Myeloma Research Foundation (MMRF) and Gene Expression Omnibus (GEO) databases were analyzed to identify lncRNAs linked to MM patient survival. A risk assessment model stratified patients into high- and low-risk groups, and survival was evaluated. Additionally, a triple-ceRNA (lncRNA–miRNA–mRNA) network was constructed, and functional analysis was performed. The research also involved immune function analysis and chemotherapy drug sensitivity assessment using oncoPredict and the GDSC dataset. Results We identified 422 lncRNAs significantly associated with overall survival in MM patients and ultimately focused on the 6 with the highest prognostic value. These lncRNAs were used to develop a risk score formula that stratified patients into high- and low-risk groups. Kaplan–Meier analysis revealed shorter survival in high-risk patients. We integrated this lncRNA signature with clinical parameters to construct a nomogram for predicting MM prognosis. Additionally, a triple-ceRNA network was constructed to reveal potential miRNA targets, coding genes related to these lncRNAs and significantly enriched pathways. Immune checkpoint gene expression and immune cell composition were also analyzed in relation to the lncRNA risk score. Finally, using the oncoPredict tool, we observed that high-risk patients exhibited decreased sensitivity to key MM chemotherapeutics, suggesting that lncRNA profiles are linked to chemotherapy resistance.

Osteoarthritis (OA) is a common degenerative joint disorder that adversely affects the quality of life of patients. Identification of novel diagnostic biomarkers is pivotal for the early detection and prevention of OA. Dataset GSE185059 was selected from Gene Expression Omnibus database to obtain differentially expressed lncRNAs (DE-lncRNAs), mRNAs (DE-mRNAs), and circRNAs (DE-circRNAs) between OA and normal samples. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses as well as protein–protein interaction (PPI) network construction of DE-mRNAs were conducted. Hub genes were identified from PPI networks and validated by RT-qPCR. starBase database was utilized for predicting miRNAs binding with hub genes, selected DE-lncRNAs and DE-circRNAs, respectively. The competing endogenous RNA (ceRNA) networks were constructed. A total of 818 DE-mRNAs, 191 DE-lncRNAs, and 2053 DE-circRNAs were identified. The DE-mRNAs were significantly enriched in several inflammation-related GO terms and KEGG pathways such as positive regulation of cell–cell adhesion, TNF-alpha signaling pathway and NF-kappa B signaling pathway. Thirteen hub genes were identified, which were CFTR, GART, SMAD2, NCK1, TJP1, UBE2D1, EFTUD2, PRKACB, IL10, SNRPG, CHD4, RPS24, and SRSF6. OA-related DE-lncRNA/circRNA-miRNA-hub gene networks were constructed. We identified 13 hub genes and constructed the ceRNA networks related to OA, providing a theoretical basis for further research. [ABSTRACT FROM AUTHOR]

This article, titled "RETRACTED: Extracellular Vesicles Carry lncRNA SNHG16 to Promote Metastasis of Breast Cancer Cells via the miR-892b/PPAPDC1A Axis," was published in Frontiers in Cell & Developmental Biology. The study investigated the role of extracellular vesicles (EVs) in breast cancer metastasis. It found that EVs derived from breast cancer cells transferred a specific long non-coding RNA (lncRNA) called SNHG16 to promote the migration, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells. The study also identified the miR-892b/PPAPDC1A axis as the mechanism through which SNHG16 exerted its effects. However, it is important to note that this article has been retracted. [Extracted from the article]

In recent years, burgeoning research has underscored the pivotal role of noncoding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein-protein interaction networks, mRNA-lncRNA co-expression networks, and circRNA-microRNA-mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field. [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]

Purpose: Multiple myeloma (MM) is the second most common hematologic malignancy, and there is no cure for this disease. This study aimed to explore the prognostic value of long noncoding RNAs (lncRNAs) in MM and to reveal related immune and chemotherapy resistance mechanisms. Methods: In this study, lncRNA profiles from the Multiple Myeloma Research Foundation (MMRF) and Gene Expression Omnibus (GEO) databases were analyzed to identify lncRNAs linked to MM patient survival. A risk assessment model stratified patients into high- and low-risk groups, and survival was evaluated. Additionally, a triple-ceRNA (lncRNA–miRNA–mRNA) network was constructed, and functional analysis was performed. The research also involved immune function analysis and chemotherapy drug sensitivity assessment using oncoPredict and the GDSC dataset. Results: We identified 422 lncRNAs significantly associated with overall survival in MM patients and ultimately focused on the 6 with the highest prognostic value. These lncRNAs were used to develop a risk score formula that stratified patients into high- and low-risk groups. Kaplan–Meier analysis revealed shorter survival in high-risk patients. We integrated this lncRNA signature with clinical parameters to construct a nomogram for predicting MM prognosis. Additionally, a triple-ceRNA network was constructed to reveal potential miRNA targets, coding genes related to these lncRNAs and significantly enriched pathways. Immune checkpoint gene expression and immune cell composition were also analyzed in relation to the lncRNA risk score. Finally, using the oncoPredict tool, we observed that high-risk patients exhibited decreased sensitivity to key MM chemotherapeutics, suggesting that lncRNA profiles are linked to chemotherapy resistance. [ABSTRACT FROM AUTHOR]

This manuscript summarizes information on the diverse range of RNA molecules and their role as competing endogenous RNAs (ceRNAs). Moreover, it provides an overview of ceRNA regulatory networks and their applications in ruminant biology. Knowledge of co-expression networks has increased with microarrays, RNA-seq, and scRNA-seq characterizing molecular mediators across various biological scales, using sequences from numerous blood and tissue samples. By synthesizing existing knowledge, this study summarizes interactions between coding and non-coding RNAs through microRNA response elements (MREs), elucidating large-scale regulatory networks throughout the transcriptome that influence the expression and activities of various ceRNAs. Identification of non-coding RNAs with important regulatory functions will revolutionize understanding of RNA biology, shifting from an mRNA-centric model to a complex network of RNA crosstalk. The ceRNA networks offer a more comprehensive and arguably more realistic perspective compared to protein–protein interaction (PPI) networks and weighted gene co-expression networks (WGCN). These ceRNA regulatory networks can describe potential molecular regulatory mechanisms related to functional and economically important traits in ruminants, plus contribute to disease and pathology research, by elucidating pathogenesis and potential drug effects in disease and cancer models. Furthermore, they can provide insights into farm animal biology, e.g., reproductive traits in goats and sheep, regulation of fat metabolism in beef cattle, heat stress responses, and lactation regulation in dairy cattle, fertility and muscle characteristics in buffalo, and resistance to high-salt and water-deprivation conditions in camels. In conclusion, ceRNA and associated regulatory networks should promote a new understanding of molecular mechanisms and identify candidate genes and metabolic-signaling pathways in ruminants. [ABSTRACT FROM AUTHOR]

This manuscript summarizes information on the diverse range of RNA molecules and their role as competing endogenous RNAs (ceRNAs). Moreover, it provides an overview of ceRNA regulatory networks and their applications in ruminant biology. Knowledge of co-expression networks has increased with microarrays, RNA-seq, and scRNA-seq characterizing molecular mediators across various biological scales, using sequences from numerous blood and tissue samples. By synthesizing existing knowledge, this study summarizes interactions between coding and non-coding RNAs through microRNA response elements (MREs), elucidating large-scale regulatory networks throughout the transcriptome that influence the expression and activities of various ceRNAs. Identification of non-coding RNAs with important regulatory functions will revolutionize understanding of RNA biology, shifting from an mRNA-centric model to a complex network of RNA crosstalk. The ceRNA networks offer a more comprehensive and arguably more realistic perspective compared to protein–protein interaction (PPI) networks and weighted gene co-expression networks (WGCN). These ceRNA regulatory networks can describe potential molecular regulatory mechanisms related to functional and economically important traits in ruminants, plus contribute to disease and pathology research, by elucidating pathogenesis and potential drug effects in disease and cancer models. Furthermore, they can provide insights into farm animal biology, e.g., reproductive traits in goats and sheep, regulation of fat metabolism in beef cattle, heat stress responses, and lactation regulation in dairy cattle, fertility and muscle characteristics in buffalo, and resistance to high-salt and water-deprivation conditions in camels. In conclusion, ceRNA and associated regulatory networks should promote a new understanding of molecular mechanisms and identify candidate genes and metabolic-signaling pathways in ruminants.

Abstract 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.

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]

Introduction: Low-temperature stress negatively impacts rice yield, posing a significant risk to food security. While previous studies have explored the physiological and linear gene expression alterations in rice under lowtemperature conditions, the changes in competing endogenous RNA (ceRNA) networks remain largely unexamined. Methods: We conducted RNA sequencing on two japonica rice varieties with differing cold-tolerance capabilities to establish ceRNA networks. This enabled us to investigate the transcriptional regulatory network and molecular mechanisms that rice employs in response to low-temperature stress. Results: We identified 364 differentially expressed circular RNAs (circRNAs), 224 differentially expressed microRNAs (miRNAs), and 12,183 differentially expressed messenger RNAs (mRNAs). WRKY family was the most prominent transcription factor family involved in cold tolerance. Based on the expression patterns and targeted relationships of these differentially expressed RNAs, we discerned five potential ceRNA networks related to low-temperature stress in rice: osa-miR166j-5p from the miR166 family was associated with cold tolerance; osa-miR528-3p and osa-miR156j-3p were linked to stress response; and osa-miR156j-3p was involved in the antioxidant system. In addition, Os03g0152000 in the antioxidant system, as well as Os12g0491800 and Os05g0381400, correlated with the corresponding stress response and circRNAs in the network. A gene sequence difference analysis and phenotypic validation of Os11g0685700 (OsWRKY61) within the WRKY family suggested its potential role in regulating cold tolerance in rice. Discussion and conclusion: We identified Os11g0685700 (OsWRKY61) as a promising candidate gene for enhancing cold tolerance in japonica rice. The candidate miRNAs, mRNAs, and circRNAs uncovered in this study are valuable targets for researchers and breeders. Our findings will facilitate the development of cold-tolerant rice varieties from multiple angles and provide critical directions for future research into the functions of cold-tolerancerelated miRNAs, mRNAs, and circRNAs in rice. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been identified in diverse cancers for their role in regulating multiple cellular processes by antagonizing microRNAs (miRNAs or miRs). However, the role of circRNA hsa_circ_0000092 in hepatocellular carcinoma (HCC) still remains enigmatic. Therefore, we aimed to investigate the specific mechanism of hsa_circ_0000092 in HCC. Differentially expressed circRNAs associated to HCC were initially analysed. The expression of hsa_circ_0000092, miR‐338‐3p and HN1 in HCC tissues and cell lines was examined. Next, the interaction among hsa_circ_0000092, miR‐338‐3p and HN1 was determined by dual‐luciferase reporter, RNA pull‐down and northern blot assays. Subsequently, a series of mimic, inhibitor or siRNA plasmids were delivered into HCC cells to validate the effects of hsa_circ_0000092, miR‐338‐3p and HN1 in controlling cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, the role of hsa_circ_0000092 in tumour growth of HCC in vivo was assessed with hsa_circ_0000092 depleted with siRNA. The hsa_circ_0000092/miR‐338‐3p/HN1 axis was predicted to participate in the development of HCC. hsa_circ_0000092 and HN1 were highly expressed while miR‐338‐3p was poorly expressed in HCC tissues and cell lines. hsa_circ_0000092 could competitively bind to miR‐338‐3p to up‐regulate HN1 expression. Moreover, depleted hsa_circ_0000092 or elevated miR‐338‐3p was shown to suppress HCC cell proliferation, migration, invasion and angiogenesis in vitro via down‐regulation of HN1. Furthermore, silencing hsa_circ_0000092 was demonstrated to suppress tumour growth in HCC in vivo. The results of this study suggested that hsa_circ_0000092 impaired miR‐338‐3p‐mediated HN1 inhibition to aggravate the development of HCC, indicating that hsa_circ_0000092 is a potential candidate marker and therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is one of the most common malignant neoplasms worldwide. Competing endogenous RNA (ceRNA) networks may identify potential biomarkers associated with the progression and prognosis of BC. The OCT4-pg5/miR-145-5p/OCT4B ceRNA network was found to be related to the progression and prognosis of BC. OCT4-pg5 expression was significantly higher in BC cell lines than in normal bladder cells, with OCT4-pg5 expression correlating with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, whereas miR-145-5p suppressed these activities. The 3' untranslated region (3'UTR) of OCT4-pg5 competed for miR-145-5p, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted epithelial-mesenchymal transition (EMT) by activating the Wnt/β-catenin pathway and upregulating the expression of matrix metalloproteinases (MMPs) 2 and 9 as well as the transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. The OCT4-pg5/miR-145-5p/OCT4B axis promotes the progression of BC by inducing EMT via the Wnt/β-catenin pathway and enhances cisplatin resistance. This axis may represent a therapeutic target in patients with BC. [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]

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high mortality and poor prognosis. Despite intensive research focused on tumor suppression, the 5‐year survival rate of ESCC is lower than 15%. Therefore, investigate fundamental mechanisms involved in ESCC is on‐demand crucial for diagnostics and developing targeted therapeutic drugs. Circular RNAs (circRNAs), as an emerging class of non‐coding RNA, have been elucidated that circRNAs participated in regulating a variety of pathological processes and tumorigenesis. Nevertheless, the functional role of circRNAs in the occurrence and development of ESCC remains unclear. We identify a novel circRNA (hsa_circ_0001707), which was highly expressed in ESCC patients' tissues and cell lines. Furthermore, gain‐ and loss‐of‐function assays were performed and found that overexpression of hsa_circ_0001707 significantly promote tumor proliferation, metastasis, and invasion. By functioning as a competing endogenous RNA (ceRNA), the dual‐luciferase activity assay verified that hsa_circ_0001707 can endogenously bind with miR‐203a‐3p and regulate its downstream gene Snail2. Rescue assay further confirms that hsa_circ_0001707 downregulation could partially attenuate the facilitation effect of miR‐203a‐3p, thereby inhibiting the endothelial‐mesenchymal transition (EMT) process of ESCC. Our results suggested that hsa_circ_0001707 play an oncogenic role in the pathogenesis of ESCC, which might be a potential biomarker for diagnostics and targeting therapy. [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]

The current situation of hepatocellular carcinoma (HCC) management is challenging due to its high incidence, mortality, recurrence and metastasis. Recent advances in gene genetic and expression regulation have unveiled the significant role of non-coding RNA (ncRNA) in various cancers. This led to the formulation of the competing endogenous RNA (ceRNA) hypothesis, which posits that both coding RNA and ncRNA, containing miRNA response elements (MRE), can share the same miRNA sequence. This results in a competitive network between ncRNAs, such as lncRNA and mRNA, allowing them to regulate each other. Extensive research has highlighted the crucial role of the ceRNA network in HCC development, impacting various cellular processes including proliferation, metastasis, cell death, angiogenesis, tumor microenvironment, organismal immunity, and chemotherapy resistance. Additionally, the ceRNA network, mediated by lncRNA or circRNA, offers potential in early diagnosis and prevention of HCC. Consequently, ceRNAs are emerging as therapeutic targets for HCC. The complexity of these gene networks aligns with the multi-target approach of traditional Chinese medicine (TCM), presenting a novel perspective for TCM in combating HCC. Research is beginning to show that TCM compounds and prescriptions can affect HCC progression through the ceRNA network, inhibiting proliferation and metastasis, and inducing apoptosis. Currently, the lncRNAs TUG1, NEAT1, and CCAT1, along with their associated ceRNA networks, are among the most promising ncRNAs for HCC research. [ABSTRACT FROM AUTHOR]

Introduction: Menstrual blood-derived stem cells (MenSCs) are vital in treating many degenerative and traumatic disorders. However, the underlying molecular mechanisms remain obscure in MenSCs-treating spinal cord injury (SCI) rats. Methods: MenSCs were adopted into the injured sites of rat spinal cords at day 7 post surgery and the tissues were harvested for total RNA sequencing analysis at day 21 after surgery to investigate the expression patterns of RNAs. The differentially expressed genes (DEGs) were analyzed with volcano and heatmap plot. DEGs were sequentially analyzed by weighted gene coexpression network, functional enrichment, and competitive endogenous RNAs (ceRNA) network analysis. Next, expression of selected miRNAs, lncRNAs, circRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics packages and extra databases were enrolled to scoop the genes functions and their interaction relationships. Results: A total of 89 lncRNAs, 65 circRNAs, 120 miRNAs and 422 mRNAs were significantly upregulated and 65 lncRNAs, 72 circRNAs, 74 miRNAs, and 190 mRNAs were significantly downregulated in the MenSCs treated rats compared to SCI ones. Current investigation revealed that MenSCs treatment improve the recovery of the injured rats and the most significantly involved pathways in SCI regeneration were cell adhesion molecules, nature killer cell mediated cytotoxicity, primary immunodeficiency, chemokine signaling pathway, T cell receptor signaling pathway and B cell receptor signaling pathway. Moreover, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA ceRNA network of SCI was constructed. Finally, the protein-protein interaction (PPI) network was constructed using the top 100 DE mRNAs. The constructed PPI network included 47 nodes and 70 edges. Discussion: In summary, the above results revealed the expression profile and potential functions of differentially expressed (DE) RNAs in the injured spinal cords of rats in the MenSCs-treated and SCI groups, and this study may provide new clues to understand the mechanisms of MenSCs in treating SCI. [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]

Small cell lung cancer (SCLC) is characterized by early metastatic dissemination and rapid emergence of chemoresistance resulting in a very dismal prognosis. SCLC tumors are characterized by nearly universal biallelic inactivation of TP53 and RB1 genes and are classified into four molecular subtypes based on the expression of lineage-specific transcription factors. The integration of information encoded by the coding and non-coding genome has significantly improved our understanding of the contribution of various non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), in the pathogenesis of SCLC. This has led to the concept of competing endogenous RNAs (ceRNAs) where the presence of the same miRNA response elements in one or more coding and ncRNAs may result in them competing for the same miRNA. Several studies have looked at the role of lncRNAs and circRNAs as ceRNAs by constructing ceRNA regulatory networks (ceRNETs). In this review, we discuss the role of ceRNETs in regulating various cancer hallmarks, including cell proliferation, invasion, migration, EMT, apoptosis, and chemoresistance of SCLC cells. We also discuss the potential of lncRNAs and circRNAs as biomarkers for diagnosis, prognosis, and predicting chemoresistance of SCLC.

Background: Hepatocellular carcinoma (HCC) continues to endanger human health worldwide. Regulatory networks of competing endogenous RNAs (ceRNAs) play important roles in HCC. TP53 is the second most often altered gene in HCC and has a significant role in regulating target genes such as miRNAs and lncRNAs. Methods: Data from patients with TP53 mutation were collected through the cBioPortal database and differential analysis was performed to screen RNAs related to TP53 mutation. The lncRNA-miRNA–mRNA relationship was predicted by the miRcode, miRDB, and TargetScan databases. The ceRNA networks were screened and visualized by Cytoscape. Core ceRNA networks were generated by differential analysis, coexpression analysis, prognostic analysis and subcellular localization. Finally, methylation, mutation, PPI, GSEA, immunity and drug sensitivity analyses of MEX3A were performed to determine the role of MEX3A in HCC. Results: We identified 1508 DEmRNAs, 85 DEmiRNAs and 931 DElncRNAs and obtained a ceRNA network including 28 lncRNAs, 4 miRNAs and 31 mRNAs. Twenty hub DERNAs in the TP53-altered-related ceRNA network were screened out by Cytoscape and the core ceRNA network (LINC00491/TCL6-hsa-miR-139-5p-MEX3A) was obtained by multiple analyses. In addition, we discovered that the methylation level of MEX3A was decreased and the mutation frequency was raised in HCC. Furthermore, elevated MEX3A expression was associated with alterations in the HCC immunological microenvironment. Conclusion: We successfully constructed a reciprocal ceRNA network, which could provide new ideas for exploring HCC mechanisms and therapeutic approaches.

Abstract 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.

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]

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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.

The prognosis of patients with advanced renal cell carcinoma (RCC) has improved with newer therapies, including molecular-targeted therapies and immuno-oncology agents. Despite these therapeutic advances, many patients with metastatic disease remain uncured. Inhibition of glycogen synthase kinase-3β (GSK-3β) is a promising new therapeutic strategy for RCC; however, the precise regulatory mechanism has not yet been fully elucidated. MicroRNAs (miRNAs) act as post-translational regulators of target genes, and we investigated the potential regulation of miRNAs on GSK-3β in RCC. We selected nine candidate miRNAs from three databases that could potentially regulate GSK-3β. Among these, hsa-miR-4465 (miR-4465) was downregulated in RCC cell lines and renal cancer tissues. Furthermore, luciferase assays revealed that miR-4465 directly interacted with the 3′ untranslated region of GSK-3β, and Western blot analysis showed that overexpression of miR-4465 significantly decreased GSK-3β protein expression. Functional assays showed that miR-4465 overexpression significantly suppressed cell invasion of A498 and Caki-1 cells; however, cell proliferation and migration were suppressed only in Caki-1 and A498 cells, respectively, with no effect on cell cycle and apoptosis. In conclusion, miR-4465 regulates GSK-3β expression but does not consistently affect RCC cell function as a single molecule. Further comprehensive investigation of regulatory networks is required in this field.

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.

Introduction: IgA nephropathy (IgAN) is a prevalent worldwide glomerular disease with a complex pathophysiology that has significant economic implications. Despite the lack of successful research, this study aims to discover the potential competing endogenous RNA (ceRNA) network of autophagy-associated genes in IgAN and examine their correlation with immune cell infiltration. Methods: Autophagy-related hub genes were discovered by assessing the GSE116626 dataset and constructing a protein-protein interaction network. Nephroseq v5 analysis engine was used to analyze correlations between hub genes and proteinuria, glomerular filtration rate (GFR), and serum creatinine levels. Then, a ceRNA network construction and the CIBERSORT tool for immune cell infiltration analysis were also performed. Additionally, the differentially expressed autophagy-related genes were used to predict potential targeted medications for IgAN. Results: Overall, 1,396 differentially expressed genes were identified in IgAN along with 25 autophagy-related differentially expressed messenger RNAs. Enrichment analysis revealed significant involvement of autophagy and apoptosis in biological processes. Next, we evaluated the top hub nodes based on their highest degrees. The ability of IgAN discrimination was confirmed in the GSE35487 and GSE37460 datasets by validating the five hub genes: SIRT1, FOS, CCL2, CDKN1A, and MYC. In the Nephroseq v5 analysis engine, the clinical correlation of the five hub genes was confirmed. Furthermore, the ceRNA network identified 18 circular RNAs and 2 microRNAs associated with hub autophagy-related genes in IgAN. Our investigation identified hsa-miR-32-3p and hsa-let-7i-5p as having elevated expression levels and substantial diagnostic value. Finally, four distinctively infiltrated immune cells were found to be associated with the hub autophagy-related genes, and 67 drugs were identified as potential therapeutic options for IgAN. Conclusion: This study sheds light on a novel ceRNA regulatory network mechanism associated with autophagy in IgAN development.

Abstract 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 Background The differential expression of circular RNAs (circRNAs) in individuals with very severe chronic obstructive pulmonary disease (COPD) and healthy individuals was screened using microarray technology. The related functions and mechanisms were analyzed using bioinformatic methods to explore the potential of target circRNAs as biomarkers of COPD and provide insights for future pathogenesis. Patients and methods Thirty patients with very severe COPD and thirty healthy controls were diagnosed at The Second People’s Hospital of Hefei from September 2021 to September 2022. The differential expression of circRNAs was compared and analyzed using a gene microarray and verified using quantitative real-time polymerase chain reaction (qRT-PCR) technology. Results A total of 90 upregulated and 29 downregulated circRNAs were screened in patients with very severe COPD and compared with those in healthy controls. qRT-PCR analysis showed that hsa_circ_0062683 of patients with very severe COPD was significantly upregulated, and hsa_circ_0089763 and hsa_circ_0008882 were significantly downregulated. By constructing the circRNA-miRNA interaction network, it was found that hsa-miR-612, hsa-miR-593-5p, hsa-miR-765, and hsa-miR-103a-2-5p are the miRNAs regulated by more differentially expressed circRNAs (DEcircRNAs). DEcircRNAs may participate in the development of COPD through hypoxia or regulation of various immune cells. Conclusion Plasma circRNAs may play a helpful role in the diagnosis and assessment of COPD and be valuable disease biomarkers.

Abstract 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 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.

Bladder cancer is a common disease associated with high rates of morbidity and mortality. Although immunotherapy approaches such as adoptive T-cell therapy and immune checkpoint blockade have been investigated for the treatment of bladder cancer, their off-target effects and ability to affect only single targets have led to clinical outcomes that are far from satisfactory. Therefore, it is important to identify novel targets that can effectively control tumor growth and metastasis. It is well known that long noncoding RNAs (lncRNAs) are powerful regulators of gene expression. Increasing evidence has shown that dysregulated lncRNAs in bladder cancer are involved in cancer cell proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). In this review, we focus on the roles and underlying mechanisms of lncRNA-mediated competing endogenous RNA (ceRNA) networks in the regulation of bladder cancer progression. In addition, we discuss the potential of targeting lncRNA-mediated ceRNA networks to overcome cancer treatment resistance and its association with clinicopathological features and outcomes in bladder cancer patients. We hope this review will stimulate research to develop more effective therapeutic approaches for bladder cancer treatment.

Accumulating evidence showed that competing endogenous RNA (ceRNA) mechanism plays a pivotal role in salt sensitivity of blood pressure (SSBP). We constructed a ceRNA network based on SSBP-related differently expressed lncRNAs (2), mRNAs (73) and miRNAs (18). Bioinformatic analyses were utilized to analyze network and found network genes participate in biological pathways related to SSBP pathogenesis such as regulation of nitric oxide biosynthetic process (GO:0045,428) and cellular response to cytokine stimulus (GO:0071,345). Fourteen candidate ceRNA pathways were selected from network to perform qRT-PCR validation and found nine RNAs (KCNQ1OT1, SLC8A1-AS1, IL1B, BCL2L11, KCNJ15, CX3CR1, KLF2, hsa-miR-362–5p and hsa-miR-423–5p) differently expressed between salt-sensitive (SS) and salt-resistant (SR) groups (P

Background: Acute myeloid leukemia (AML) is characterized by a high recurrence and mortality rate. Cuproptosis is involved in cell death regulation in in a variety of solid tumors. Long non-coding RNAs that regulate cuproptosis genes in the pathogenesis of acute leukemia have yet to be explored. Methods: First, cuproptosis genes with distinct expression levels were discovered by contrasting AML with normal samples from the TCGA and GTEx cohorts. Pearson correlation and univariate Cox-regression analysis were performed to identify cuproptosis-associated lncRNAs with significant prognostic values. Then the least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to establish a multi-gene signature to predict AML prognosis. Next, Kaplan-Meier estimator, receiver operating characteristic curve, and a nomogram were performed to evaluate the predictive capacity of the risk signature. Functional enrichment analyses were employed to assess their function. Moreover, qRT-PCR testing of lncRNA expression in AML samples was conducted. The competing endogenous RNA (ceRNA) network was constructed to find the target genes. Results: A risk model based on the signature of three cuproptosis-associated lncRNAs was developed. The results showed that the model possessed excellent prognostic potential. The nomogram raised the accuracy in predicting AML survival. In addition, functional enrichment analyses demonstrated an enrichment of inflammatory and immune-related pathways. Moreover, correlations between the risk signature and clinicopathological variables, tumor mutational burden, RNA stemness score, immune profile, and drug sensitivity were observed. Furthermore, we discovered that TRAF3IP2-AS1 may function as a ceRNA to regulate cuproptosis and ferroptosis gene expression. Conclusion: The risk signature established in this study could serve as a reliable biosignature for AML prognosis. And the findings presented here may facilitate research on cuproptosis in AML.