circRNA Expression Research Articles

Knockdown of circ-Gatad1 alleviates LPS induced HK2 cell injury via targeting miR-22-3p/TRPM7 axis in septic acute kidney

BackgroundSepsis is a life-threatening, systemic inflammatory disease that can lead to a variety of conditions, including septic acute kidney injury (AKI). Recently, multiple circular Rnas (circRNAs) have been implicated in the development of this disease.MethodsIn this study, we aimed to elucidate the role of circ-Gatad1 in sepsis induced AKI and its potential mechanism of action. High-throughput sequencing was used to investigate abnormal expression of circRNA in AKI and healthy volunteer. Bioinformatics analysis and luciferase reporting analysis were used to clarify the interacted relationship among circRNA, miRNA and mRNA. HK2 cells were treated with lipopolysaccharide (LPS) to establish septic AKI cell model. HK2 cells were employ to analysis the ROS, inflammatory cytokines expression, proliferation and apoptosis under LPS condition.ResultsThe result show that the expression of circ-Gatad1 was increased in septic acute kidney patients. Downregulation circ-Gatad1 suppressed LPS-treated induced HK2 cells injury including apoptosis, proliferation ability, ROS and inflammatory cytokines level. Bioinformatics and luciferase report analysis confirmed that both miR-22-3p and TRPM7 were downstream targets of circ-Gatad1. Overexpression of TRPM7 or downregulation of miR-22-3p reversed the protective effect of si-circ-Gatad1 to HK2 after exposure to LPS (5 µg/ml) microenvironment.ConclusionIn conclusion, knockdown of circ-Gatad1 alleviates LPS induced HK2 cell injury via targeting miR-22-3p/TRPM7 axis in septic acute kidney.

Circular RNA Expression of Peripheral Blood Mononuclear Cells Associated with Risk of Acute Exacerbation in Smoking Chronic Obstructive Pulmonary Disease.

Circular RNAs (circRNAs) are newly identified endogenous non-coding RNAs that function as crucial gene modulators in the development of several diseases. By assessing the expression levels of circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD), this study attempted to find new biomarkers for COPD screening. We confirmed altered circRNA expression in PBMCs of COPD (n=41) vs controls (n=29). Further analysis focused on the highest and lowest circRNA expression levels. The T-test is used to assess the statistical variances in circRNAs among COPD patients in the smoking and non-smoking cohorts. Additionally, among smokers, the Spearman correlation test assesses the association between circRNAs and clinical indicators. Two circRNAs, hsa_circ_0042590 and hsa_circ_0049875, that were highly upregulated and downregulated in PBMCs from COPD patients were identified and verified. Smokers with COPD had lower hsa_circ_0042590 and higher hsa_circ_0049875, in comparison to non-smokers. There was a significant correlation (r=0.52, P<0.01) between the number of acute exacerbations (AEs) that smokers with COPD experienced in the previous year and the following year (r=0.67, P<0.001). Moreover, hsa_circ_0049875 was connected to the quantity of AEs in the year prior (r=0.68, P<0.0001) as well as the year after (r=0.72, P<0.0001). AUC: 0.79, 95% CI: 0.1210-0.3209, P<0.0001) for hsa_circ_0049875 showed a strong diagnostic value for COPD, according to ROC curve analysis. Hsa_circ_0042590 showed a close second with an AUC of 0.83 and 95% CI: -0.1972--0.0739 (P <0.0001). This research identified a strong correlation between smoking and hsa_circ_0049875 and hsa_circ_0042590 in COPD PBMCs. The number of AEs in the preceding and succeeding years was substantially linked with the existence of hsa_circ_0042590 and hsa_circ_0049875 in COPD patients who smoke. Additionally, according to our research, hsa_circ_0049875 and hsa_circ_0042590 may be valuable biomarkers for COPD diagnosis.

Hijacking and rewiring of host CircRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) regulatory networks by oncoviruses during development of viral cancers.

A significant portion of human cancers are caused by oncoviruses (12%-25%). Oncoviruses employ various strategies to promote their replication and induce tumourigenesis in host cells, one of which involves modifying the gene expression patterns of the host cells, leading to the rewiring of genes and resulting in significant changes in cellular processes and signalling pathways. In recent studies, a specific mode of gene regulation known as circular RNA (circRNA)-mediated competing endogenous RNA (ceRNA) networks has emerged as a key player in this context. CircRNAs, a class of non-coding RNA molecules, can interact with other RNA molecules, such as mRNAs and microRNAs (miRNAs), through a process known as ceRNA crosstalk. This interaction occurs when circRNAs, acting as sponges, sequester miRNAs, thereby preventing them from binding to their target mRNAs and modulating their expression. By rewiring the host cell genome, oncoviruses have the ability to manipulate the expression and activity of circRNAs, thereby influencing the ceRNA networks that can profoundly impact cellular processes such as cell proliferation, differentiation, apoptosis, and immune responses. This review focuses on a comprehensive evaluation of the latest findings on the involvement of virus-induced reprogramming of host circRNA-mediated ceRNA networks in the development and pathophysiology of human viral cancers, including cervical cancer, gastric cancer, nasopharyngeal carcinoma, Kaposi's sarcoma, hepatocellular carcinoma, and diffuse large B cell lymphoma. Understanding these mechanisms can improve our knowledge of how oncoviruses contribute to human tumourigenesis and identify potential targets for developing optimised therapies and diagnostic tools for viral cancers.

The novel circRNA circ_0045881 inhibits cell proliferation and invasion by targeting mir-214-3p in triple-negative breast cancer

BackgroundTriple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer (BC). The circRNA-miRNA‒mRNA axis is a promising biomarker for the early diagnosis and prognosis of BC. However, the critical circRNA mediators involved in TNBC progression and the underlying regulatory mechanism involved remain largely unclear.MethodsIn this study, we carried out a circRNA microarray analysis of 6 TNBC patients and performed a gene ontology (GO) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to characterize important circRNAs involved in TNBC progression. The interaction between circRNAs and miRNAs was determined by dual luciferase and RNA immunoprecipitation (RIP) assays. Moreover, Transwell, wound healing and Cell Counting Kit-8 (CCK8) assays were performed with altered circRNA or miRNA expression in MDA-MB-231 and BT-549 cells to investigate the roles of these genes in cell invasion, migration and proliferation.ResultsA total of 78 circRNAs were differentially expressed in TNBC tissues, and the hsa_circ_0045881 level was significantly decreased in TNBC tissues and cells. Lentivirus-mediated hsa_circ_0045881 overexpression in MDA-MB-231 and BT-549 cells significantly reduced cell invasion and migration capacity. Additionally, hsa_circ_0045881 interacted with miR-214-3p in MDA-MB-231 cells. miR-214-3p mimics in MDA-MB-231 and BT-549 cells significantly enhanced cell invasion, migration and proliferation, but the other combinations of inhibitors had opposite effects on cell activity.ConclusionsOur data indicated that the circRNA has_circ_0045881 plays key roles in TNBC progression and that hsa_circ_0045881 might act as a sponge for miR-214-3p to modulate its levels in TNBC cells, thereby regulating cell invasion, metastasis and proliferation. hsa_circ_004588 might be a potential prognostic marker and therapeutic target for TNBC.

Circular RNA as a source of neoantigens for cancer vaccines

BackgroundThe effectiveness of somatic neoantigen-based immunotherapy is often hindered by the limited number of mutations in tumors with low to moderate mutation burden. Focusing on microsatellite-stable colorectal cancer (CRC), this...

Comprehensive Analysis of circRNA, lncRNA, miRNA and mRNA Expression Profiles and Their Competing Endogenous RNA Networks in Hepatitis B Virus-Related Hepatocellular Carcinoma.

Pursuing knowledge about circular RNA (circRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression profiles and their competing endogenous RNA (ceRNA) networks in hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) was the focus of this research. Expression patterns of circRNAs, lncRNAs, miRNAs, and mRNAs were searched for in relation to HBV-related HCC using whole-transcriptome sequencing. The expression levels of chosen circRNA, lncRNA, miRNA, and mRNA were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The potential connections and roles of ceRNA were deduced via bioinformatics research. The sum of 284 circRNAs, 2,927 lncRNAs, 693 miRNAs, and 5566 mRNAs were discovered to be expressed at considerably different levels in HBV-related HCC tissue and adjacent normal tissue. And the most significantly up- and down-regulated circRNAs, lncRNAs, miRNAs, and mRNAs were verified in HBV-related HCC by qRT-PCR. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of HBV-related HCC were established, and the ceRNA regulatory networks revealed the gene expression mechanisms controlled by ncRNAs. Collectively, we revealed the contribution of various circRNA, lncRNA, miRNA, and mRNA expression profiles and identified their ceRNA regulatory networks in HBV-related HCC, providing a theoretical basis for further exploration.

Understanding Circular RNAs in Health, Welfare, and Productive Traits of Cattle, Goats, and Sheep.

Circular RNAs (circRNAs) are unique noncoding RNA molecules, notable for their covalent closed-loop structures, which play a crucial role in regulating gene expression across a variety of biological processes. This review comprehensively synthesizes the existing knowledge of circRNAs in three key livestock species: Bos taurus (cattle), Ovis aries (sheep), and Capra hircus (goats). It focuses on their functional importance and emerging potential as biomarkers for disease detection, stress response, and overall physiological health. Specifically, it delves into the expression and functionality of circRNAs in these species, paying special attention to traits critical to livestock productivity such as milk production, meat quality, muscle development, wool production, immune responses, etc. We also address the current challenges faced in circRNA research, including the need for standardized methodologies and broader studies. By providing insights into the molecular mechanisms regulated by circRNAs, this review underscores their scientific and economic relevance in the livestock industry. The potential of circRNAs to improve animal health management and the quality of animal-derived products aligns with growing consumer concerns for animal welfare and sustainability. Thus, this paper aims to guide future research directions while supporting the development of innovative strategies in livestock management and breeding.

Mm9_circ_014683 regulates microglia polarization through canonical NFκB signaling pathway in diabetic retinopathy

Diabetic retinopathy (DR) is still the major cause of visual loss in working-aged people, one of the critical pathological processes are retinal microglia-mediated inflammation. Our previous study demonstrated that enhanced M1 microglial polarization was involved in retinal inflammation in DR, but the detailed mechanism needs further investigation. Circular RNAs (circRNAs) are important kind of noncoding RNAs involved in the regulation of various cell biological processes. Herein, the circRNA expression profiles of BV2 mouse microglia treated with or without glucose were detected, and a total of 347 differentially expressed circRNAs were identified in glucose-treated BV2 cells. The key circRNA mm9_circ_014683 increased after glucose stimulation. Inhibiting or overexpressing mm9_circ_014683 showed no effect on the proliferation and apoptosis of microglia. Inhibiting mm9_circ_014683 impeded M1 polarization and promoted M2 polarization, and overexpressing mm9_circ_014683 showed the opposite effect. A total of 216 differentially expressed genes were identified in mm9_circ_014683-knockdown BV2 cells, which were enriched in several signaling pathways, including the NFκB signaling pathway. Moreover, mm9_circ_014683 positively regulated the canonical, NFκB signaling pathway. Besides, mm9_circ_014683 was highly expressed in the retinal microglia of diabetic mice, and intraocular injection of Lv-circRNA inhibited M1 but enhanced M2 retinal microglial polarization. In conclusion, mm9_circ_014683 regulates microglial polarization through the canonical NFκB signaling pathway in diabetic retinopathy. This study may provide insight into the pathogenesis and treatment of DR.

CircRNA_102046 Affects the Occurrence and Development of Ischemic Stroke by Regulating the miR-493-5p/ROCK1 Signaling.

In our previous studies, the results have revealed that circRNA_102046 is significantly upregulated in plasma of patients with ischemic stroke, which closely related to NIHSS score. Human neural stem cells (hNSCs) were used for characterization and subcellular localization of circRNA_102046, and hNSCs OGD/R model was generated. The proliferation of cells was examined by CCK-8 assay. The expression levels of associated molecules were evaluated using RT-qPCR, immunofluorescence staining or western blotting. The binding and co-localization of associated molecules were also evaluated by RIP and FISH assay. Furthermore, MCAO mouse model was established to examine the effects of circRNA_102046 on the progression of ischemic stroke. Expression of circRNA_102046 was detected in the cytoplasma of hNSCs. Then OGD/R cell model was established, where the levels of circRNA_102046 was significantly up-regulated. Furthermore, knockdown of circRNA_102046 was able to enhance the proliferation and differentiation of OGD/R hNSCs. In further downstream molecular studies, the results indicated that circRNA_102046 could participate in the occurrence and development of ischemic stroke through targeting miR-493-5p. In addition, ROCK1 was identified as the putative target of miR-493-5p, and circRNA_102046 regulates the proliferation and differentiation of hNSCs via the miR-493-5p/ROCK1 signaling. More importantly, the infarct volumes of MCAO mice were remarkably reduced after the treatment with sh-circRNA_102046, which also up- and down-regulate the expression of miR-493-5p and ROCK1, respectively. Elucidating this novel pathway provides a theoretical basis for the development of new diagnostic approach and targeted treatment for ischemic stroke.

A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway

BackgroundClear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer with high aggressive phenotype and poor prognosis. Accumulating evidence suggests that circRNAs have been identified as pivotal mediators in cancers. However, the role of circRNAs in ccRCC progression remains elusive.MethodsThe differentially expressed circRNAs in 4 paired human ccRCC and adjacent noncancerous tissues ccRCC were screened using circRNA microarrays and the candidate target was selected based on circRNA expression level using weighted gene correlation network analysis (WGCNA) and the gene expression omnibus (GEO) database. CircPDHK1 expression in ccRCC and adjacent noncancerous tissues (n = 148) were evaluated along with clinically relevant information. RT-qPCR, RNase R digestion, and actinomycin D (ActD) stability test were conducted to identify the characteristics of circPDHK1. The subcellular distribution of circPDHK1 was analyzed by subcellular fractionation assay and fluorescence in situ hybridization (FISH). Immunoprecipitation-mass spectrometry (IP-MS) and immunofluorescence (IF) were employed to evaluate the protein-coding ability of circPDHK1. ccRCC cells were transfected with siRNAs, plasmids or lentivirus approach, and cell proliferation, migration and invasion, as well as tumorigenesis and metastasis in nude mice were assessed to clarify the functional roles of circPDHK1 and its encoded peptide PDHK1-241aa. RNA-sequencing, western blot analysis, immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) assays were further employed to identify the underlying mechanisms regulated by PDHK1-241aa.ResultsCircPDHK1 was upregulated in ccRCC tissues and closely related to WHO/ISUP stage, T stage, distant metastasis, VHL mutation and Ki-67 levels. CircPDHK1 had a functional internal ribosome entry site (IRES) and encoded a novel peptide PDHK1-241aa. Functionally, we confirmed that PDHK1-241aa and not the circPDHK1 promoted the proliferation, migration and invasion of ccRCC. Mechanistically, circPDHK1 was activated by HIF-2A at the transcriptional level. PDHK1-241aa was upregulated and interacted with PPP1CA, causing the relocation of PPP1CA to the nucleus. This thereby inhibited AKT dephosphorylation and activated the AKT-mTOR signaling pathway.ConclusionsOur data indicated that circPDHK1-encoded PDHK1-241aa promotes ccRCC progression by interacting with PPP1CA to inhibit AKT dephosphorylation. This study provides novel insights into the multiplicity of circRNAs and highlights the potential use of circPDHK1 or PDHK1-241aa as a therapeutic target for ccRCC.

CircRNA expression profiles and regulatory networks in the vitreous humor of people with high myopia

Myopia is a global health and economic issue. Circular RNAs (circRNAs) have been shown to play an important role in the pathogenesis of many ocular diseases. We first evaluated the circRNA profiles and possible roles in vitreous humor samples of individuals with high myopia by a competitive endogenous RNA (ceRNA) array. Vitreous humor samples were collected from 15 high myopic (5 for ceRNA array, and 10 for qPCR) and 15 control eyes (5 for ceRNA array, and 10 for qPCR) with idiopathic epiretinal membrane (ERM) and macular hole (MH). 486 circRNAs (339 upregulated and 147 downregulated) and 264 mRNAs (202 upregulated and 62 downregulated) were differentially expressed between the high myopia and control groups. The expression of hsa_circ_0033079 (hsa-circDicer1), hsa_circ_0029989 (hsa-circNbea), hsa_circ_0019072 (hsa-circPank1) and hsa_circ_0089716 (hsa-circEhmt1) were validated by qPCR. Pearson analysis and multivariate regression analysis showed positive and significant correlations for axial length with hsa-circNbea and hsa-circPank1. KEGG analysis showed that the target genes of circRNAs were enriched in the mTOR, insulin, cAMP, and VEGF signaling pathways. GO analysis indicated that circRNAs mainly targeted transcription, cytoplasm, and protein binding. CircRNA-associated ceRNA network analysis and PPI network analysis identified several critical genes for myopia. The expression of circNbea, circPank1, miR-145-5p, miR-204-5p, Nras, Itpr1 were validated by qPCR in the sclera of form-deprivation myopia (FDM) mice model. CircPank1/miR-145-5p/NRAS and circNbea/miR-204-5p/ITPR1 were identified and may be important in the progression of myopia. Our findings suggest that circRNAs may contribute to the pathogenesis of myopia and may serve as potential biomarkers.

CircBRIP1: a plasma diagnostic marker for non-small-cell lung cancer

BackgroundCircular RNA (circRNA), which has been demonstrated in studies to be abundantly prevalent in tumor cells and bodily fluids and to play a significant role in tumors, has the potential for biological markers to be used to assist tumor diagnosis. This study mainly discusses the potential of circBRIP1 as a biomarker for diagnosing non-small-cell lung cancer (NSCLC).MethodsFirst, high-throughput sequencing screened the differentially expressed circBRIP1, and real-time fluorescence quantitative PCR (qRT-PCR) verified its expression in NSCLC. Next, sanger sequencing, agarose gel electrophoresis, RNase R assay, and fluorescence in situ hybridization (FISH) were used to verify its molecular characteristics. The diagnostic value was analyzed by the subject operating characteristic curve (ROC), and the cardinality test was analyzed for correlation with clinicopathological parameters. Finally, we tentatively predicted the downstream miRNA- or RNA-binding protein that may bind to circBRIP1.ResultsCircBRIP1 is highly expressed in NSCLC tissues, cells and plasma with good specificity and stability. CircBRIP1 not only can well-distinguish NSCLC patients from benign pulmonary diseases (BPD) patients, healthy individuals and small cell lung cancer (SCLC) patients, but it also has some potential for dynamic monitoring. Combined with the analysis of clinicopathological data, the high level of circRNA expression was related to the degree of tumor differentiation, TNM stage, T stage, lymph node metastasis and distal metastasis in NSCLC patients. In addition, circBRIP1 has a high diagnostic value.ConclusionsPlasma circBRIP1 is significantly overexpressed in NSCLC patients. It can be used as a sensitive biomarker with unique value for early diagnosis, tumor development and prognosis detection.

Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery

BackgroundExosomes (Exos) generated from bone mesenchymal stem cells (BMSCs) are elucidated to enhance cutaneous wound healing in mice models of diabetes mellitus (DM). While underlying mechanisms remain unknown.MethodsNext-generation sequencing (NGS) was used to examine changes in circRNA expression levels following Exo treatment. Luciferase assays were used to determine the interactions between RNAs. Immunofluorescence staining was used to examine reactive oxygen species (ROS) in endothelial progenitor cells (EPCs) cultured in high glucose (HG) conditions. Therapeutic effects regarding Exos were also examined by immunofluorescence.ResultsWe found that Exo treatment enhanced cutaneous wound healing significantly. NGS indicated that circ-Snhg11 was involved in Exo-mediated tissue repairing. Downregulation of circ-Snhg11 decreased Exo-mediated therapy responses during wound healing in diabetic mouse. Our luciferase reporter data confirmed that SLC7A11 and miR-144-3p were circ-Snhg11 downstream targets. miR-144-3p overexpression or SLC7A11 knockdown altered the protective effects of circ-Snhg11 upon EPCs exposed to HG conditions. Upregulation of circ-Snhg11 incremented therapy effects of Exo treatment during wound healing in DM mice through enhanced angiogenesis along with a reduction in GPX4-mediated ferroptosis.Conclusionscirc-Snhg11 in BMSC-Exos enhanced SLC7A11/GPX4-mediated anti-ferroptosis signals via miR-144-3p sponging resulting in enhanced diabetic wound healing and improved angiopoiesis.

A therapeutical insight into the correlation between circRNAs and signaling pathways involved in cancer pathogenesis.

Pre-messenger RNA molecules are back-spliced to create circular RNAs, which are non-coding RNA molecules. After a thorough investigation, it was discovered that these circRNAs have critical biological roles. CircRNAs have a variety of biological functions, including their ability to operate as microRNA sponges, interact with proteins to alter their stabilities and activities, and provide templates for the translation of proteins. Evidence supports a link between the emergence of numerous diseases, including various cancer types, and dysregulated circRNA expression. It is commonly known that a significant contributing element to cancer development is the disruption of numerous molecular pathways essential for preserving cellular and tissue homeostasis. The dysregulation of multiple biological processes is one of the hallmarks of cancer, and the molecular pathways linked to these processes are thought to be promising targets for therapeutic intervention. The biological and carcinogenic effects of circRNAs in the context of cancer are thoroughly reviewed in this article. Specifically, we highlight circRNAs' involvement in signal transduction pathways and their possible use as novel biomarkers for the early identification and prognosis of human cancer.

Expression profiles of host miRNAs and circRNAs and ceRNA network during Toxoplasma gondii lytic cycle

Toxoplasma gondii is an opportunistic protozoan parasite that is highly prevalent in the human population and can lead to adverse health consequences in immunocompromised patients and pregnant women. Noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), play important regulatory roles in the pathogenesis of many infections. However, the differentially expressed (DE) miRNAs and circRNAs implicated in the host cell response during the lytic cycle of T. gondii are unknown. In this study, we profiled the expression of miRNAs and circRNAs in human foreskin fibroblasts (HFFs) at different time points after T. gondii infection using RNA sequencing (RNA-seq). We identified a total of 7, 7, 27, 45, 70, 148, 203, and 217 DEmiRNAs and 276, 355, 782, 1863, 1738, 6336, 1229, and 1680 DEcircRNAs at 1.5, 3, 6, 9, 12, 24, 36, and 48 h post infection (hpi), respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the DE transcripts were enriched in immune response, apoptosis, signal transduction, and metabolism-related pathways. These findings provide new insight into the involvement of miRNAs and circRNAs in the host response to T. gondii infection.

Research Progress of Circular RNA in Acute Myeloid Leukemia --Review

Acute myeloid leukemia(AML) is a malignant tumor of the blood system that is highly heterogeneous in terms of pathogenesis, genetic background and prognostic outcome, with an extremely high fatality rate and recurrence rate. Therefore, exploring new treatment methods and diagnostic strategies is one of the ways to improve the survival rate of patients with acute myeloid leukemia. Circular RNA (circRNA) is a special kind of noncoding RNA, which plays an important role in gene transcription, translation and epigenetic modification, and participates in the disease progression and prognosis of multiple solid tumors. At present, it has found that the abnormal expression of circRNA is closely related to the occurrence, development, drug resistance and prognosis of acute myeloid leukemia.Clinically, it can be used as a new biomarker and potential therapeutic target for AML. This article briefly reviews the research progress of circRNA in acute myeloid leukemia, aiming to provide new strategies for optimizing the diagnosis, treatment and prognosis of leukemia.

The Function of Circular RNAs in Myocardial Ischemia-Reperfusion Injury: Underlying Mechanisms and Therapeutic Advancement.

Myocardial ischemia reperfusion injury (MIRI) represents a prevalent and severe cardiovascular condition that arises primarily after myocardial infarction recanalization, cardiopulmonary bypass surgery, and both stable and unstable angina pectoris. MIRI can induce malignant arrhythmias and heart failure, thereby increasing the morbidity and mortality rates associated with cardiovascular diseases. Hence, it is important to assess the potential pathological mechanisms of MIRI and develop effective treatments. The role of circular RNAs (circRNAs) in MIRI has increasingly become a topic of interest in recent years. Moreover, significant evidence suggests that circRNAs play a critical role in MIRI pathogenesis, thereby representing a promising therapeutic target. This review aimed to provide a comprehensive overview of the current understanding of the role of circRNAs in MIRI and discuss the mechanisms through which circRNAs contribute to MIRI development and progression, including their effects on apoptosis, inflammation, oxidative stress, and autophagy. Furthermore, the potential therapeutic applications of circRNAs in MIRI treatment, including the use of circRNA-based therapies and modulation of circRNA expression levels, have been explored. Overall, this paper highlights the importance of circRNAs in MIRI and underscores their potential as novel therapeutic targets.

Circ-phkb promotes cell apoptosis and inflammation in LPS-induced alveolar macrophages via the TLR4/MyD88/NF-kB/CCL2 axis

BackgroundCircular RNAs (CircRNAs) have been associated with acute lung injury (ALI), but their molecular mechanisms remain unclear.MethodsThis study developed a rat model of lipopolysaccharide (LPS)-induced ALI and evaluated the modeling effect by hematoxylin and eosin staining, Masson’s trichrome staining, lung wet-to-dry weight ratio, terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA) detection of inflammatory factors (interleukin-1β, tumor necrosis factor alpha, and interleukin-6). Using lung tissues from a rat model of LPS-induced ALI, we then conducted circRNA sequencing, mRNA sequencing, and bioinformatics analysis to obtain differential circRNA and mRNA expression profiles as well as potential ceRNA networks. Furthermore, we performed quantitative real-time polymerase chain reaction (qRT-PCR) assays to screen for circ-Phkb in ALI rat lung tissues, alveolar macrophages, and LPS-induced NR8383 cells. We conducted induction with or without LPS with circ-Phkb siRNA and overexpression lentivirus in NR8383. Cell Counting Kit-8, C5-Ethynyl-2′-deoxyuridine (Edu), TUNEL, and cytometry were used to identify proliferation and apoptosis, respectively. We detected inflammatory factors using ELISA. Finally, we used Western blot to detect the apoptosis-related proteins and TLR4/MyD88/NF-kB/CCL2 pathway activation.ResultsOur results revealed that both circRNA and mRNA profiles are different from those of the Sham group. We observed a significant circ-Phkb upregulation in NR8383 cells and LPS-exposed rats. Apoptosis and inflammation were greatly reduced when circ-Phkb expression was reduced in NR8383 cells, cell proliferation was increased, and circ-Phkb overexpression was decreased.ConclusionsIn terms of mechanism, circ-Phkb suppression inhibits CCL2 expression via the TLR4/MyD88/NF-kB pathway in LPS-induced alveolar macrophages.

Investigation of Circular RNA Expression Profiles in Ultrasound-guided Incomplete Radiofrequency Ablation Transplanted Tumor Models of Human Liver Cancer.

Abnormally expressed circular RNAs (circRNAs) are associated with many diseases and have important biological effects on the regulation of gene expression. However, the circRNA expression profile in incomplete radiofrequency ablation (RFA)-treated liver cancer (LC) patients has not been characterized. This study investigated the potential biological effects of differentially expressed (DE) circRNAs in an incomplete RFA-treated transplantation tumor model of human LC. A circRNA microarray was utilized to analyze changes in the circRNA expression profiles. CircRNA host gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also conducted using computational biology. Quantitative real-time PCR (qPCR) was also performed on the selected DE-circRNAs to verify the reliability of the microarray. The circRNA/miRNA interactions were predicted by Arraystar software and confirmed by a dual-luciferase assay. Following RFA incomplete ablation, 76 DE-circRNAs were detected (|fold change |>1.5, P-value < 0.05), 21 of which were upregulated and 55 of which were downregulated. Computational biological analysis revealed that the T-cell receptor signaling pathway was the most significantly enriched pathway of the genes related to altered expression, as indicated by enrichment of LCK, AKT3 and DLG1. PCR results for the upregulated hsa_circRNA_103595 and downregulated hsa_circRNA_001264 indicated that the circRNA microarray sequencing results were reliable. Double luciferase reporter assays confirmed that hsa-miR-185-3p was the target miRNA of hsa_circRNA_103595. The current study confirmed the changes in the expression profiles of circRNAs in tumor transplantation models after incomplete ablation, these changes may play a crucial role in the pathophysiological process of residual cancer transplantation tumors. These findings could lead to new directions for investigating the molecular biological mechanisms underlying RFA-treated LC as well as new ideas for treating LC by regulating circRNAs.

Circular RNAs: Regulators of endothelial cell dysfunction in atherosclerosis.

Endothelial cell (EC) dysfunction is associated with atherosclerosis. Circular RNAs (circRNAs) are covalently closed loops formed by back-splicing, are highly expressed in a tissue-specific or cell-specific manner, and regulate ECs mainly through miRNAs (mircoRNAs) or protein sponges. This review describes the regulatory mechanisms and physiological functions of circRNAs, as well as the differential expression of circRNAs in aberrant ECs. This review focuses on their roles in inflammation, proliferation, migration, angiogenesis, apoptosis, senescence, and autophagy in ECs from the perspective of signaling pathways, such as nuclear factor κB (NF-κB), nucleotide-binding domain, leucine-rich-repeat family, pyrin-domain-containing 3 (NLRP3)/caspase-1, Janus kinase/signal transducer and activator of transcription (JAK/STAT), and phosphoinositide-3 kinase/protein kinase B (PI3K/Akt). Finally, we address the issues and recent advances in circRNAs as well as circRNA-mediated regulation of ECs to improve our understanding of the molecular mechanisms underlying the progression of atherosclerosis and provide a reference for studies on circRNAs that regulate EC dysfunction and thus affect atherosclerosis.