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Objective: Competitive endogenous RNA (ceRNA) networks have uncovered a novel mode of RNA interaction, and are implicated in various biological processes and the pathogenesis of IS. This study aimed to explore the potential mechanisms underlying the ceRNA network in IS. Methods: Four public datasets containing lncRNA and mRNA (GSE22255 and GSE16561) and miRNA (GSE55937 and GSE43618) expression profiles from the GEO database were systematically analyzed to explore the role of RNAs in ischemic stroke (IS). Differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) between IS and normal control samples were identified. LncRNA-miRNA and miRNA-mRNA interactions were predicted, and the competing endogenous RNA (ceRNA) regulatory network was constructed using the Cytoscape software. The correlation between the RNAs in the ceRNA network and the clinical features of the samples was evaluated. Finally, principal component analysis was performed on the RNAs that constitute the ceRNA regulatory network, and their differential expression and principal component relationships among different types of samples were observed. Results: A total of 224 DEmRNAs, 7 DEmiRNAs, and four DElncRNAs related to IS in four datasets were identified. Then, through target gene prediction, a lncRNA–miRNA–mRNA ceRNA network that contained 3 DElncRNAs, 2 DEmiRNAs, and 24 DEmRNAs was constructed. Correlations of the clinical characteristics showed that PART1 and SERPINH1 were related to clinical diseases, WNK1 was related to lifestyle, and seven RNAs were related to age. PCA results indicate that three principal components of PC1, PC2, and PC3 can clearly distinguish between control and IS samples. Conclusion: Overall, we constructed a ceRNA network in IS, which could offer insights into the molecular mechanism and potential prognostic biomarkers for further research.

ABSTRACT: Quail, as an advantageous avian model organism due to its compact size and short reproductive cycle, holds substantial potential for enhancing our understanding of skeletal muscle development. The quantity of skeletal muscle represents a vital economic trait in poultry production. Unraveling the molecular mechanisms governing quail skeletal muscle development is of paramount importance for optimizing meat and egg yield through selective breeding programs. However, a comprehensive characterization of the regulatory dynamics and molecular control underpinning quail skeletal muscle development remains elusive. In this study, through the application of HE staining on quail leg muscle sections, coupled with preceding fluorescence quantification PCR of markers indicative of skeletal muscle differentiation, we have delineated embryonic day 9 (E9) and embryonic day 14 (E14) as the start and ending points, respectively, of quail skeletal muscle differentiation. Then, we employed whole transcriptome sequencing to investigate the temporal expression profiles of leg muscles in quail embryos at the initiation of differentiation (E9) and upon completion of differentiation (E14). Our analysis revealed the expression patterns of 12,012 genes, 625 lncRNAs, 14,457 circRNAs, and 969 miRNAs in quail skeletal muscle samples. Differential expression analysis between the E14 and E9 groups uncovered 3,479 differentially expressed mRNAs, 124 lncRNAs, 292 circRNAs, and 154 miRNAs. Furthermore, enrichment analysis highlighted the heightened activity of signaling pathways related to skeletal muscle metabolism and intermuscular fat formation, such as the ECM-receptor interaction, focal adhesion, and PPAR signaling pathway during E14 skeletal muscle development. Conversely, the E9 stage exhibited a prevalence of pathways associated with myoblast proliferation, exemplified by cell cycle processes. Additionally, we constructed regulatory networks encompassing lncRNA‒mRNA, miRNA‒mRNA, lncRNA‒miRNA-mRNA, and circRNA-miRNA‒mRNA interactions, thus shedding light on their putative roles within quail skeletal muscle. Collectively, our findings illuminate the gene and non-coding RNA expression characteristics during quail skeletal muscle development, serving as a foundation for future investigations into the regulatory mechanisms governing non-coding RNA and quail skeletal muscle development in poultry production.

Synaptic dysfunction and neuronal damage have been extensively associated with diabetic retinopathy (DR). Our group evidenced that chronic hyperglycemia reduces the retinal expression of presynaptic proteins, which are crucial for proper synaptic function. The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Transcriptome analysis was performed, comparing the retinas of 10 diabetic (db/db) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily and the retinas of 10 additional db/db mice that received vehicle eye drops. Ten non-diabetic mice (db/+) were used as a control group. The Gene Ontology (GO) and Reactome databases were used to perform the gene set enrichment analysis (GSEA) in order to explore the most enriched biological pathways among the groups. The most differentiated genes of these pathways were validated through quantitative RT-PCR. Transcriptome analysis revealed that sitagliptin eye drops have a significant effect on retinal expression patterns and that neurotransmission is the most enriched biological process. Our study evidenced enriched pathways that contain genes involved in membrane trafficking, transmission across chemical synapses, vesicle-mediated transport, neurotransmitter receptors and postsynaptic signal transmission with negative regulation of signaling as a consequence of neuroprotector treatment with sitagliptin. This improves the modulation of the macromolecule biosynthetic process with positive regulation of cell communication, which provides beneficial effects for the neuronal metabolism. This study suggests that topical administration of sitagliptin ameliorates the abnormalities on presynaptic and postsynaptic signal transmission during experimental DR and that this improvement is one of the main mechanisms behind the previously demonstrated beneficial effects. [ABSTRACT FROM AUTHOR]

Abstract Background Hypoxia-induced pulmonary hypertension (HPH) is a lethal cardiovascular disease with the characteristic of severe remodeling of pulmonary vascular. Although a large number of dysregulated mRNAs, lncRNAs, circRNAs, and miRNAs related to HPH have been identified from extensive studies, the competitive endogenous RNA (ceRNA) regulatory network in the pulmonary artery that responds to hypoxia remains largely unknown. Results Transcriptomic profiles in the pulmonary arteries of HPH rats were characterized through high-throughput RNA sequencing in this study. Through relatively strict screening, a set of differentially expressed RNAs (DERNAs) including 19 DEmRNAs, 8 DElncRNAs, 19 DEcircRNAs, and 23 DEmiRNAs were identified between HPH and normal rats. The DEmRNAs were further found to be involved in cell adhesion, axon guidance, PPAR signaling pathway, and calcium signaling pathway, suggesting their crucial role in HPH. Moreover, a hypoxia-induced ceRNA regulatory network in the pulmonary arteries of HPH rats was constructed according to the ceRNA hypothesis. More specifically, the ceRNA network was composed of 10 miRNAs as hub nodes, which might be sponged by 6 circRNAs and 7 lncRNAs, and directed the expression of 18 downstream target genes that might play important role in the progression of HPH. The expression patterns of selected DERNAs in the ceRNA network were then validated to be consistent with sequencing results in another three independent batches of HPH and normal control rats. The diagnostic effectiveness of several hub mRNAs in ceRNA network was further evaluated through investigating their expression profiles in patients with pulmonary artery hypertension (PAH) recorded in the Gene Expression Omnibus (GEO) dataset GSE117261. Dysregulated POSTN, LTBP2, SPP1, and LSAMP were observed in both the pulmonary arteries of HPH rats and lung tissues of PAH patients. Conclusions A ceRNA regulatory network in the pulmonary arteries of HPH rats was constructed, 10 hub miRNAs and their corresponding interacting lncRNAs, circRNAs, and mRNAs were identified. The expression patterns of selected DERNAs were further validated to be consistent with the sequencing result. POSTN, LTBP2, SPP1, and LSAMP were suggested to be potential diagnostic biomarkers and therapeutic targets for PAH.

Quail, as an advantageous avian model organism due to its compact size and short reproductive cycle, holds substantial potential for enhancing our understanding of skeletal muscle development. The quantity of skeletal muscle represents a vital economic trait in poultry production. Unraveling the molecular mechanisms governing quail skeletal muscle development is of paramount importance for optimizing meat and egg yield through selective breeding programs. However, a comprehensive characterization of the regulatory dynamics and molecular control underpinning quail skeletal muscle development remains elusive. In this study, through the application of HE staining on quail leg muscle sections, coupled with preceding fluorescence quantification PCR of markers indicative of skeletal muscle differentiation, we have delineated embryonic day 9 (E9) and embryonic day 14 (E14) as the start and ending points, respectively, of quail skeletal muscle differentiation. Then, we employed whole transcriptome sequencing to investigate the temporal expression profiles of leg muscles in quail embryos at the initiation of differentiation (E9) and upon completion of differentiation (E14). Our analysis revealed the expression patterns of 12,012 genes, 625 lncRNAs, 14,457 circRNAs, and 969 miRNAs in quail skeletal muscle samples. Differential expression analysis between the E14 and E9 groups uncovered 3,479 differentially expressed mRNAs, 124 lncRNAs, 292 circRNAs, and 154 miRNAs. Furthermore, enrichment analysis highlighted the heightened activity of signaling pathways related to skeletal muscle metabolism and intermuscular fat formation, such as the ECM-receptor interaction, focal adhesion, and PPAR signaling pathway during E14 skeletal muscle development. Conversely, the E9 stage exhibited a prevalence of pathways associated with myoblast proliferation, exemplified by cell cycle processes. Additionally, we constructed regulatory networks encompassing lncRNA‒mRNA, miRNA‒mRNA, lncRNA‒miRNA-mRNA, and circRNA-miRNA‒mRNA interactions, thus shedding light on their putative roles within quail skeletal muscle. Collectively, our findings illuminate the gene and non-coding RNA expression characteristics during quail skeletal muscle development, serving as a foundation for future investigations into the regulatory mechanisms governing non-coding RNA and quail skeletal muscle development in poultry production. [ABSTRACT FROM AUTHOR]

Objectives: Long non-coding RNAs (lncRNAs) are key regulators involved in the progression of glioma, and many functional lncRNAs are yet to be identified. This study aimed to explore the function of CHRM3-AS2, a rarely reported lncRNA, in glioma, as well as the underlying mechanisms involving miR-370-5p/KLF4. Methods: Differentially expressed RNAs (DERs) were screened from two gene expression profiles of glioblastoma (GBM). Fluorescence in situ hybridisation was performed to determine the subcellular localisation of CHRM3-AS2. Cell viability, colony formation, apoptosis, migration, and invasion were evaluated using cell counting kit-8, colony counts, flow cytometry, wound healing, and Transwell assays, respectively. mRNA and protein expression of specific genes were measured using quantitative real-time polymerase chain reaction and western blotting, respectively. Dual luciferase reporter gene, RNA immunoprecipitation, and RNA pull-down assays were performed to identify the target relationships. A mouse xenograft model was established for in vivo validation. Results: CHRM3-AS2 was screened as a prognosis-associated DER in GBM. CHRM3-AS2 expression was up-regulated in glioma cells, and CHRM3-AS2 was localised in the cytoplasm. Silencing of CHRM3-AS2 expression inhibited cell viability, colony formation, migration, and invasion and promoted apoptosis of U251 and SHG-44 cells. In addition, CHRM3-AS2 targeted miR-370-5p/KLF4 in glioma cells. The anti-tumour effect of CHRM3-AS2 silencing was weakened by miR-370-5p silencing or KLF4 overexpression. In vivo , silencing of CHRM3-AS2 expression inhibited tumour growth and Ki67 expression in mice. Overexpression of KLF4 also weakened the anti-tumour effect of CHRM3-AS2 silencing in mice. Conclusions: Silencing of CHRM3-AS2 expression inhibited the malignant progression of glioma by regulating miR-370-5p/KLF4 expression. [ABSTRACT FROM AUTHOR]

Background: Hypoxia-induced pulmonary hypertension (HPH) is a lethal cardiovascular disease with the characteristic of severe remodeling of pulmonary vascular. Although a large number of dysregulated mRNAs, lncRNAs, circRNAs, and miRNAs related to HPH have been identified from extensive studies, the competitive endogenous RNA (ceRNA) regulatory network in the pulmonary artery that responds to hypoxia remains largely unknown. Results: Transcriptomic profiles in the pulmonary arteries of HPH rats were characterized through high-throughput RNA sequencing in this study. Through relatively strict screening, a set of differentially expressed RNAs (DERNAs) including 19 DEmRNAs, 8 DElncRNAs, 19 DEcircRNAs, and 23 DEmiRNAs were identified between HPH and normal rats. The DEmRNAs were further found to be involved in cell adhesion, axon guidance, PPAR signaling pathway, and calcium signaling pathway, suggesting their crucial role in HPH. Moreover, a hypoxia-induced ceRNA regulatory network in the pulmonary arteries of HPH rats was constructed according to the ceRNA hypothesis. More specifically, the ceRNA network was composed of 10 miRNAs as hub nodes, which might be sponged by 6 circRNAs and 7 lncRNAs, and directed the expression of 18 downstream target genes that might play important role in the progression of HPH. The expression patterns of selected DERNAs in the ceRNA network were then validated to be consistent with sequencing results in another three independent batches of HPH and normal control rats. The diagnostic effectiveness of several hub mRNAs in ceRNA network was further evaluated through investigating their expression profiles in patients with pulmonary artery hypertension (PAH) recorded in the Gene Expression Omnibus (GEO) dataset GSE117261. Dysregulated POSTN, LTBP2, SPP1, and LSAMP were observed in both the pulmonary arteries of HPH rats and lung tissues of PAH patients. Conclusions: A ceRNA regulatory network in the pulmonary arteries of HPH rats was constructed, 10 hub miRNAs and their corresponding interacting lncRNAs, circRNAs, and mRNAs were identified. The expression patterns of selected DERNAs were further validated to be consistent with the sequencing result. POSTN, LTBP2, SPP1, and LSAMP were suggested to be potential diagnostic biomarkers and therapeutic targets for PAH. [ABSTRACT FROM AUTHOR]

Abstract Background Hypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension, which seriously affect people’s life. The purpose of this study was to identify the potential biomarkers of HTN and understand its possible mechanisms. Methods The dataset numbered GSE28260 related to hypertensive and normotensive was downloaded from NCBI Gene Expression Omnibus. Then, the differentially expressed RNAs (DERs) were screened using R limma package, and functional analyses of DE-mRNA were performed by DAVID. Afterwards, a ceRNA network was established and KEGG pathway was analyzed based on the Gene Set Enrichment Analysis (GSEA) database. Finally, a ceRNA regulatory network directly associated with HTN was proposed. Results A total of 947 DERs were identified, including 900 DE-mRNAs, 20 DE-lncRNAs and 27 DE-miRNAs. Based on these DE-mRNAs, they were involved in biological processes such as fatty acid beta-oxidation, IRE1-mediated unfolded protein response, and transmembrane transport, and many KEGG pathways like glycine, serine and threonine metabolism, carbon metabolism. Subsequently, lncRNAs KCTD21-AS1, LINC00470 and SNHG14 were found to be hub nodes in the ceRNA regulatory network. KEGG analysis showed that insulin signaling pathway, glycine, serine and threonine metabolism, pathways in cancer, lysosome, and apoptosis was associated with hypertensive. Finally, insulin signaling pathway was screened to directly associate with HTN and was regulated by mRNAs PPP1R3C, PPKAR2B and AKT3, miRNA has-miR-107, and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG. Conclusions Insulin signaling pathway was directly associated with HTN, and miRNA has-miR-107 and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG were the biomarkers of HTN. These results would improve our understanding of the occurrence and development of HTN.

ObjectivesLong non-coding RNAs (lncRNAs) are key regulators involved in the progression of glioma, and many functional lncRNAs are yet to be identified. This study aimed to explore the function of CHRM3-AS2, a rarely reported lncRNA, in glioma, as well as the underlying mechanisms involving miR-370-5p/KLF4.MethodsDifferentially expressed RNAs (DERs) were screened from two gene expression profiles of glioblastoma (GBM). Fluorescence in situ hybridisation was performed to determine the subcellular localisation of CHRM3-AS2. Cell viability, colony formation, apoptosis, migration, and invasion were evaluated using cell counting kit-8, colony counts, flow cytometry, wound healing, and Transwell assays, respectively. mRNA and protein expression of specific genes were measured using quantitative real-time polymerase chain reaction and western blotting, respectively. Dual luciferase reporter gene, RNA immunoprecipitation, and RNA pull-down assays were performed to identify the target relationships. A mouse xenograft model was established for in vivo validation.ResultsCHRM3-AS2 was screened as a prognosis-associated DER in GBM. CHRM3-AS2 expression was up-regulated in glioma cells, and CHRM3-AS2 was localised in the cytoplasm. Silencing of CHRM3-AS2 expression inhibited cell viability, colony formation, migration, and invasion and promoted apoptosis of U251 and SHG-44 cells. In addition, CHRM3-AS2 targeted miR-370-5p/KLF4 in glioma cells. The anti-tumour effect of CHRM3-AS2 silencing was weakened by miR-370-5p silencing or KLF4 overexpression. In vivo, silencing of CHRM3-AS2 expression inhibited tumour growth and Ki67 expression in mice. Overexpression of KLF4 also weakened the anti-tumour effect of CHRM3-AS2 silencing in mice.ConclusionsSilencing of CHRM3-AS2 expression inhibited the malignant progression of glioma by regulating miR-370-5p/KLF4 expression.

Synaptic dysfunction and neuronal damage have been extensively associated with diabetic retinopathy (DR). Our group evidenced that chronic hyperglycemia reduces the retinal expression of presynaptic proteins, which are crucial for proper synaptic function. The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Transcriptome analysis was performed, comparing the retinas of 10 diabetic (db/db) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily and the retinas of 10 additional db/db mice that received vehicle eye drops. Ten non-diabetic mice (db/+) were used as a control group. The Gene Ontology (GO) and Reactome databases were used to perform the gene set enrichment analysis (GSEA) in order to explore the most enriched biological pathways among the groups. The most differentiated genes of these pathways were validated through quantitative RT-PCR. Transcriptome analysis revealed that sitagliptin eye drops have a significant effect on retinal expression patterns and that neurotransmission is the most enriched biological process. Our study evidenced enriched pathways that contain genes involved in membrane trafficking, transmission across chemical synapses, vesicle-mediated transport, neurotransmitter receptors and postsynaptic signal transmission with negative regulation of signaling as a consequence of neuroprotector treatment with sitagliptin. This improves the modulation of the macromolecule biosynthetic process with positive regulation of cell communication, which provides beneficial effects for the neuronal metabolism. This study suggests that topical administration of sitagliptin ameliorates the abnormalities on presynaptic and postsynaptic signal transmission during experimental DR and that this improvement is one of the main mechanisms behind the previously demonstrated beneficial effects.

Many local sheep breeds in China have poor meat quality. Increasing intramuscular fat (IMF) content can significantly improve the quality of mutton. However, the molecular mechanisms of intramuscular adipocyte formation and differentiation remain unclear. This study compared differences between preadipocytes and mature adipocytes by whole-transcriptome sequencing and constructed systematically regulatory networks according to the relationship predicted among the differentially expressed RNAs (DERs). Sequencing results showed that in this process, there were 1,196, 754, 100, and 17 differentially expressed messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), respectively. Gene Ontology analysis showed that most DERs enriched in Cell Part, Cellular Process, Biological Regulation, and Binding terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the DERs primarily focused on Focal adhesion, phosphoinositide 3-kinase (PI3K)-Akt, mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor (PPAR) signaling pathways. Forty (40) DERs were randomly selected from the core regulatory network to verify the accuracy of the sequence data. The results of qPCR showed that the DER expression trend was consistent with sequence data. Four novel promising candidate miRNAs (miR-336, miR-422, miR-578, and miR-722) played crucial roles in adipocyte differentiation, and they also participated in multiple and important regulatory networks. We verified the expression pattern of the miRNAs and related pathways’ members at five time points in the adipocyte differentiation process (0, 2, 4, 6, 8, 10 days) by qPCR, including miR-336/ACSL4/LncRNA-MSTRG71379/circRNA0002331, miR-422/FOXO4/LncRNA-MSTRG54995/circRNA0000520, miR-578/IGF1/LncRNA-MSTRG102235/circRNA0002971, and miR-722/PDK4/LncRNA-MSTRG107440/circ RNA0002909. In this study, our data provided plenty of valuable candidate DERs and regulatory networks for researching the molecular mechanisms of sheep adipocyte differentiation and will assist studies in improving the IMF.

Many local sheep breeds in China have poor meat quality. Increasing intramuscular fat (IMF) content can significantly improve the quality of mutton. However, the molecular mechanisms of intramuscular adipocyte formation and differentiation remain unclear. This study compared differences between preadipocytes and mature adipocytes by whole-transcriptome sequencing and constructed systematically regulatory networks according to the relationship predicted among the differentially expressed RNAs (DERs). Sequencing results showed that in this process, there were 1,196, 754, 100, and 17 differentially expressed messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), respectively. Gene Ontology analysis showed that most DERs enriched in Cell Part, Cellular Process, Biological Regulation, and Binding terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the DERs primarily focused on Focal adhesion, phosphoinositide 3-kinase (PI3K)-Akt, mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor (PPAR) signaling pathways. Forty (40) DERs were randomly selected from the core regulatory network to verify the accuracy of the sequence data. The results of qPCR showed that the DER expression trend was consistent with sequence data. Four novel promising candidate miRNAs (miR-336, miR-422, miR-578, and miR-722) played crucial roles in adipocyte differentiation, and they also participated in multiple and important regulatory networks. We verified the expression pattern of the miRNAs and related pathways' members at five time points in the adipocyte differentiation process (0, 2, 4, 6, 8, 10 days) by qPCR, including miR-336/ACSL4/LncRNA-MSTRG71379/circRNA0002331, miR-422/FOXO4/LncRNA-MSTRG54995/circRNA0000520, miR-578/IGF1/LncRNA-MSTRG102235/circRNA0002971, and miR-722/PDK4/LncRNA-MSTRG107440/circ RNA0002909. In this study, our data provided plenty of valuable candidate DERs and regulatory networks for researching the molecular mechanisms of sheep adipocyte differentiation and will assist studies in improving the IMF. [ABSTRACT FROM AUTHOR]

ObjectiveTo analyze the abnormally expressed genes involved in cervical cancer occurrence and development.Materials and MethodsIntegrated bioinformatics methods were used to analyze differentially expressed (DE) RNAs, including mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), in stage I, II, III, and IV cervical cancer patients from the TCGA database to fully reveal the dynamic changes caused by cervical cancer.ResultsFirst, DE RNAs in cervical cancer tissues from stage I, II, III, and IV patients and normal cervical tissues were identified and divided into different profiles. Several DE RNA profiles were down-regulated or up-regulated in stage I, III, and IV patients. GO and KEGG analysis of DE mRNA profile 1, 2, 4, 5, 6 and 22 which were significantly down-regulated or up-regulated showed that DE mRNAs are involved in cell division, DNA replication, cell adhesion, the positive and negative regulation of RNA polymerase ll promoter transcription. Besides, DE RNA profiles with significant differences in patient stages were analyzed to perform a competing endogenous RNA (ceRNA) regulatory network of lncRNA, miRNA, and mRNA. The protein-protein interaction (PPI) network of DE mRNAs in the ceRNA regulatory network was also constructed. The network had nine central genes (up-regulated genes: CDKN2A, GSK3B, BIRC5, CYCS, MAD2L1; down-regulated genes: PTEN, FOXO3, CCND2, TGFBR2). Survival analysis found that 5 lncRNAs, 9 mRNAs, and 4 miRNAs can be used as prognostic indicators of cervical cancer. Finally, combined with cluster analysis results, we further screened 2 DE RNAs (AMZ2P1 and HDAC5) using clinical samples, suggesting that AMZ2P1, and HDAC5 may act as diagnostic biomarkers for the development of cervical cancer.ConclusionThis research provides new effective targets and reliable biological markers for the diagnosis and prognosis of cervical cancer.

Objective: To analyze the abnormally expressed genes involved in cervical cancer occurrence and development. Materials and Methods: Integrated bioinformatics methods were used to analyze differentially expressed (DE) RNAs, including mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), in stage I, II, III, and IV cervical cancer patients from the TCGA database to fully reveal the dynamic changes caused by cervical cancer. Results: First, DE RNAs in cervical cancer tissues from stage I, II, III, and IV patients and normal cervical tissues were identified and divided into different profiles. Several DE RNA profiles were down-regulated or up-regulated in stage I, III, and IV patients. GO and KEGG analysis of DE mRNA profile 1, 2, 4, 5, 6 and 22 which were significantly down-regulated or up-regulated showed that DE mRNAs are involved in cell division, DNA replication, cell adhesion, the positive and negative regulation of RNA polymerase ll promoter transcription. Besides, DE RNA profiles with significant differences in patient stages were analyzed to perform a competing endogenous RNA (ceRNA) regulatory network of lncRNA, miRNA, and mRNA. The protein-protein interaction (PPI) network of DE mRNAs in the ceRNA regulatory network was also constructed. The network had nine central genes (up-regulated genes: CDKN2A, GSK3B, BIRC5, CYCS, MAD2L1; down-regulated genes: PTEN, FOXO3, CCND2, TGFBR2). Survival analysis found that 5 lncRNAs, 9 mRNAs, and 4 miRNAs can be used as prognostic indicators of cervical cancer. Finally, combined with cluster analysis results, we further screened 2 DE RNAs (AMZ2P1 and HDAC5) using clinical samples, suggesting that AMZ2P1, and HDAC5 may act as diagnostic biomarkers for the development of cervical cancer. Conclusion: This research provides new effective targets and reliable biological markers for the diagnosis and prognosis of cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: Competitive endogenous RNA (ceRNA) networks have uncovered a novel mode of RNA interaction, and are implicated in various biological processes and the pathogenesis of IS. This study aimed to explore the potential mechanisms underlying the ceRNA network in IS., Methods: Four public datasets containing lncRNA and mRNA (GSE22255 and GSE16561) and miRNA (GSE55937 and GSE43618) expression profiles from the GEO database were systematically analyzed to explore the role of RNAs in ischemic stroke (IS). Differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) between IS and normal control samples were identified. LncRNA-miRNA and miRNA-mRNA interactions were predicted, and the competing endogenous RNA (ceRNA) regulatory network was constructed using the Cytoscape software. The correlation between the RNAs in the ceRNA network and the clinical features of the samples was evaluated. Finally, principal component analysis was performed on the RNAs that constitute the ceRNA regulatory network, and their differential expression and principal component relationships among different types of samples were observed., Results: A total of 224 DEmRNAs, 7 DEmiRNAs, and four DElncRNAs related to IS in four datasets were identified. Then, through target gene prediction, a lncRNA-miRNA-mRNA ceRNA network that contained 3 DElncRNAs, 2 DEmiRNAs, and 24 DEmRNAs was constructed. Correlations of the clinical characteristics showed that PART1 and SERPINH1 were related to clinical diseases, WNK1 was related to lifestyle, and seven RNAs were related to age. PCA results indicate that three principal components of PC1, PC2, and PC3 can clearly distinguish between control and IS samples., Conclusion: Overall, we constructed a ceRNA network in IS, which could offer insights into the molecular mechanism and potential prognostic biomarkers for further research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Competing endogenous RNAs (ceRNAs) are a newly proposed RNA interaction mechanism that has been associated with the tumorigenesis, metastasis, diagnosis, and predicting survival of various cancers. In this study, we constructed a ceRNA network in colorectal cancer (CRC). Then, we sought to develop and validate a composite clinicopathologic–genomic nomogram using The Cancer Genome Atlas (TCGA) database. To construct the ceRNA network in CRC, we analyzed the mRNAseq, miRNAseq data, and clinical information from TCGA database. LncRNA, miRNA, and mRNA signatures were identified to construct risk score as independent indicators of the prognostic value in CRC patients. A composite clinicopathologic–genomic nomogram was developed to predict the overall survival (OS). One hundred sixty-one CRC-specific lncRNAs, 97 miRNAs, and 161 mRNAs were identified to construct the ceRNA network. Multivariate Cox proportional hazards regression analysis indicated that nine-lncRNA signatures, eight-miRNA signatures, and five-mRNA signatures showed a significant prognostic value for CRC. Furthermore, a clinicopathologic–genomic nomogram was constructed in the primary cohort, which performed well in both the primary and validation sets. This study presents a nomogram that incorporates the CRC-specific ceRNA expression profile, clinical features, and pathological factors, which demonstrate its excellent differentiation and risk stratification in predicting OS in CRC patients.

Background Oxidative-stress (OS) was causal in the development of cell dysfunction and insulin resistance. Streptozotocin (STZ) was an alkylation agent that increased reactive oxygen species (ROS) levels. Here we aimed to explore the oxidative-stress and related RNAs in the liver of STZ-induced diabetic mice. Methods RNA-sequencing was performed using liver tissues from STZ induced diabetic mice and controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. The differentially expressed RNAs involved in the peroxisome pathway were validated by qRT-PCR. The glucose metabolite and OS markers were measured in the normal control (NC) and STZ-induced diabetic mellitus (DM) group. Results The levels of serum Fasting insulin, HbA1c, Malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) were significant higher in DM groups than NC group, while SOD activity decreased significantly in DM groups. We found 416 lncRNAs and 910 mRNAs were differentially expressed in the STZ-induced diabetic mice compared to the control group. OS associated RNAs were differentially expressed in the liver of STZ-induced diabetic mice. Conclusion This study confirmed that the OS was increased in the STZ-induced DM mice as evidenced by the increase of lipid peroxidation product MDA and 8-iso-PGF2α, identified aberrantly expressed lncRNAs and mRNAs in STZ-induced diabetic mice.

Competing endogenous RNAs (ceRNAs) are a newly proposed RNA interaction mechanism that has been associated with the tumorigenesis, metastasis, diagnosis, and predicting survival of various cancers. In this study, we constructed a ceRNA network in colorectal cancer (CRC). Then, we sought to develop and validate a composite clinicopathologic–genomic nomogram using The Cancer Genome Atlas (TCGA) database. To construct the ceRNA network in CRC, we analyzed the mRNAseq, miRNAseq data, and clinical information from TCGA database. LncRNA, miRNA, and mRNA signatures were identified to construct risk score as independent indicators of the prognostic value in CRC patients. A composite clinicopathologic–genomic nomogram was developed to predict the overall survival (OS). One hundred sixty-one CRC-specific lncRNAs, 97 miRNAs, and 161 mRNAs were identified to construct the ceRNA network. Multivariate Cox proportional hazards regression analysis indicated that nine-lncRNA signatures, eight-miRNA signatures, and five-mRNA signatures showed a significant prognostic value for CRC. Furthermore, a clinicopathologic–genomic nomogram was constructed in the primary cohort, which performed well in both the primary and validation sets. This study presents a nomogram that incorporates the CRC-specific ceRNA expression profile, clinical features, and pathological factors, which demonstrate its excellent differentiation and risk stratification in predicting OS in CRC patients. [ABSTRACT FROM AUTHOR]

The present study aimed to identify a long non-coding (lnc) RNAs-based signature for prognosis assessment in gastric cancer (GC) patients. By integrating gene expression data of GC and normal samples from the National Center for Biotechnology Information Gene Expression Omnibus, the EBI ArrayExpress and The Cancer Genome Atlas (TCGA) repositories, the common RNAs in Genomic Spatial Event (GSE) 65801, GSE29998, E-MTAB-1338, and TCGA set were screened and used to construct a weighted correlation network analysis (WGCNA) network for mining GC-related modules. Consensus differentially expressed RNAs (DERs) between GC and normal samples in the four datasets were screened using the MetaDE method. From the overlapped lncRNAs shared by preserved WGCNA modules and the consensus DERs, an lncRNAs signature was obtained using L1-penalized (lasso) Cox-proportional hazard (PH) model. LncRNA-mRNA networks were constructed for these signature lncRNAs, followed by functional annotation. A total of 14,824 common mRNAs and 2,869 common lncRNAs were identified in the 4 sets and 5 GC-associated WGCNA modules were preserved across all sets. MetaDE method identified 1,121 consensus DERs. A total of 50 lncRNAs were shared by preserved WGCNA modules and the consensus DERs. Subsequently, an 11-lncRNA signature was identified by LASSO-based Cox-PH model. The lncRNAs signature-based risk score could divide patients into 2 risk groups with significantly different overall survival and recurrence-free survival times. The predictive capability of this signature was verified in an independent set. These signature lncRNAs were implicated in several biological processes and pathways associated with the immune response, the inflammatory response and cell cycle control. The present study identified an 11-lncRNA signature that could predict the survival rate for GC. [ABSTRACT FROM AUTHOR]

RNAs may act as competing endogenous RNAs (ceRNAs), a critical mechanism in determining gene expression regulations in many cancers. However, the roles of ceRNAs in thyroid carcinoma remains elusive. In this study, we have developed a novel pipeline called Molecular Network-based Identification of ceRNA (MNIceRNA) to identify ceRNAs in thyroid carcinoma. MNIceRNA first constructs micro RNA (miRNA)-messenger RNA (mRNA)long non-coding RNA (lncRNA) networks from miRcode database and weighted correlation network analysis (WGCNA), based on which to identify key drivers of differentially expressed RNAs between normal and tumor samples. It then infers ceRNAs of the identified key drivers using the long non-coding competing endogenous database (lnCeDB). We applied the pipeline into The Cancer Genome Atlas (TCGA) thyroid carcinoma data. As a result, 598 lncRNAs, 1025 mRNAs, and 90 microRNA (miRNAs) were inferred to be differentially expressed between normal and thyroid cancer samples. We then obtained eight key driver miRNAs, among which hsa-mir-221 and hsa-mir-222 were key driver RNAs identified by both miRNA-mRNA-lncRNA and WGCNA network. In addition, hsa-mir-375 was inferred to be significant for patients' survival with 34 associated ceRNAs, among which RUNX2, DUSP6 and SEMA3D are known oncogenes regulating cellular proliferation and differentiation in thyroid cancer. These ceRNAs are critical in revealing the secrets behind thyroid cancer progression and may serve as future therapeutic biomarkers. [ABSTRACT FROM AUTHOR]

RNAs may act as competing endogenous RNAs (ceRNAs), a critical mechanism in determining gene expression regulations in many cancers. However, the roles of ceRNAs in thyroid carcinoma remains elusive. In this study, we have developed a novel pipeline called Molecular Network-based Identification of ceRNA (MNIceRNA) to identify ceRNAs in thyroid carcinoma. MNIceRNA first constructs micro RNA (miRNA)–messenger RNA (mRNA)long non-coding RNA (lncRNA) networks from miRcode database and weighted correlation network analysis (WGCNA), based on which to identify key drivers of differentially expressed RNAs between normal and tumor samples. It then infers ceRNAs of the identified key drivers using the long non-coding competing endogenous database (lnCeDB). We applied the pipeline into The Cancer Genome Atlas (TCGA) thyroid carcinoma data. As a result, 598 lncRNAs, 1025 mRNAs, and 90 microRNA (miRNAs) were inferred to be differentially expressed between normal and thyroid cancer samples. We then obtained eight key driver miRNAs, among which hsa-mir-221 and hsa-mir-222 were key driver RNAs identified by both miRNA–mRNA–lncRNA and WGCNA network. In addition, hsa-mir-375 was inferred to be significant for patients’ survival with 34 associated ceRNAs, among which RUNX2, DUSP6 and SEMA3D are known oncogenes regulating cellular proliferation and differentiation in thyroid cancer. These ceRNAs are critical in revealing the secrets behind thyroid cancer progression and may serve as future therapeutic biomarkers.

Synaptic dysfunction and neuronal damage have been extensively associated with diabetic retinopathy (DR). Our group evidenced that chronic hyperglycemia reduces the retinal expression of presynaptic proteins, which are crucial for proper synaptic function. The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Transcriptome analysis was performed, comparing the retinas of 10 diabetic (db/db) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily and the retinas of 10 additional db/db mice that received vehicle eye drops. Ten non-diabetic mice (db/+) were used as a control group. The Gene Ontology (GO) and Reactome databases were used to perform the gene set enrichment analysis (GSEA) in order to explore the most enriched biological pathways among the groups. The most differentiated genes of these pathways were validated through quantitative RT-PCR. Transcriptome analysis revealed that sitagliptin eye drops have a significant effect on retinal expression patterns and that neurotransmission is the most enriched biological process. Our study evidenced enriched pathways that contain genes involved in membrane trafficking, transmission across chemical synapses, vesicle-mediated transport, neurotransmitter receptors and postsynaptic signal transmission with negative regulation of signaling as a consequence of neuroprotector treatment with sitagliptin. This improves the modulation of the macromolecule biosynthetic process with positive regulation of cell communication, which provides beneficial effects for the neuronal metabolism. This study suggests that topical administration of sitagliptin ameliorates the abnormalities on presynaptic and postsynaptic signal transmission during experimental DR and that this improvement is one of the main mechanisms behind the previously demonstrated beneficial effects.

Background: Oxidative-stress (OS) was causal in the development of cell dysfunction and insulin resistance. Streptozotocin (STZ) was an alkylation agent that increased reactive oxygen species (ROS) levels. Here we aimed to explore the oxidative-stress and related RNAs in the liver of STZ-induced diabetic mice., Methods: RNA-sequencing was performed using liver tissues from STZ induced diabetic mice and controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. The differentially expressed RNAs involved in the peroxisome pathway were validated by qRT-PCR. The glucose metabolite and OS markers were measured in the normal control (NC) and STZ-induced diabetic mellitus (DM) group., Results: The levels of serum Fasting insulin, HbA1c, Malondialdehyde (MDA) and 8-iso-prostaglandin F2 α (8-iso-PGF2 α ) were significant higher in DM groups than NC group, while SOD activity decreased significantly in DM groups. We found 416 lncRNAs and 910 mRNAs were differentially expressed in the STZ-induced diabetic mice compared to the control group. OS associated RNAs were differentially expressed in the liver of STZ-induced diabetic mice., Conclusion: This study confirmed that the OS was increased in the STZ-induced DM mice as evidenced by the increase of lipid peroxidation product MDA and 8-iso-PGF2 α , identified aberrantly expressed lncRNAs and mRNAs in STZ-induced diabetic mice., Competing Interests: The authors declare there are no competing interests., (©2020 Guo et al.)

Background: Neonatal sepsis is a serious and difficult-to-diagnose systemic infectious disease occurring during the neonatal period., Objective: This study aimed to identify potential biomarkers of neonatal sepsis and explore its underlying mechanisms., Methods: We downloaded the neonatal sepsis-related gene profile GSE25504 from the NCBI Gene Expression Omnibus (GEO) database. The differentially expressed RNAs (DERs) were screened and identified using LIMMA. Then, the functions of the DERs were evaluated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, a competing endogenous RNA (ceRNA) network was constructed and functional analyses were performed., Results: The initial screening identified 444 differentially expressed (DE)-mRNAs and 45 DElncRNAs. GO analysis showed that these DE-mRNAs were involved in immune response, defense response, and positive regulation of immune system process. KEGG analysis showed that these DE-mRNAs were enriched in 30 activated pathways and 6 suppressed pathways, and those with the highest scores were the IL-17 signaling pathway and ribosome. Next, 722 miRNAs associated with the identified lncRNAs were predicted using miRWalk. A ceRNA network was constructed that included 6 lncRNAs, 11 mRNAs, and 55 miRNAs. In this network, HCP5, LINC00638, XIST and TP53TG1 were hub nodes. Functional analysis of this network identified some essential immune functions, hematopoietic functions, osteoclast differentiation, and primary immunodeficiency as associated with neonatal sepsis., Conclusion: HCP5, LINC00638, TP53TG1, ST20-AS1, and SERPINB9P1 may be potential biomarkers of neonatal sepsis and may be useful for rapid diagnosis; the biological process of the immune response was related to neonatal sepsis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)