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1.
Cell Signal ; 101: 110494, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36241055

RESUMO

Breast cancer (BC) is the most common cause of cancer-related mortality in women worldwide. Circular RNAs (circRNAs), a type of non-coding RNA, have garnered interest because of their unique looped structure. In recent years, circRNAs have been shown to be involved in various diseases, including carcinogenesis, and to serve as biomarkers for early risk assessment and survival prediction of different tumour types. This study aimed to identify a novel circRNA, hsa_circ_0000851, generated from the sixth intron of the oncogene TCF4, reported to be involved in BC pathogenesis. Our study showed that hsa_circ_0000851 was mainly located in the cytoplasm of BC cells and upregulated in BC cell lines and tissue samples. Higher hsa_circ_0000851 expression levels resulted in increased proliferation of BC cells both in vitro and in vivo, while treatment of BC cells with hsa_circ_0000851 siRNA decreased their proliferation. We found that hsa_circ_0000851 bound directly to miR-1183, accelerating the expression of its target gene PDK1, which facilities BC cell proliferation and migration through PDK1/p-AKT.


Assuntos
Neoplasias da Mama , MicroRNAs , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , RNA Circular/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias da Mama/patologia , Neoplasias de Mama Triplo Negativas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Linhagem Celular Tumoral
2.
Cancer Lett ; 553: 215980, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36336149

RESUMO

Cholangiocarcinoma (CCA) is the most common primary biliary malignancy with an adverse prognosis. Although its incidence is relatively low, early diagnosis is difficult due to the lack of specific symptoms. Current treatment options for CCA are limited, resulting in a low curative rate. Circular RNAs (circRNAs) have become a new research hotspot in recent years, and they are frequently dysregulated in CCA and may become therapeutic targets and prognostic biomarkers of CCA. Accumulating evidence has demonstrated that numerous dysregulated circRNAs are vital players in the etiopathogenesis of CCA. Aberrant expression of specific circRNAs was correlated with unfavourable clinical characteristics in CCA. Many studies have found that circRNAs are involved in the progression and development of CCA through various mechanisms, including competitive inhibition of miRNAs via the competing endogenous RNA (ceRNA) network, interaction with RNA-binding proteins (RBPs), activation of cancer-related signalling pathways, and regulation of proteins and peptides. Additionally, some circRNAs are involved in the inflammatory microenvironment of CCA and play a crucial role in chemotherapy drug resistance. Thus, they are essential for the early diagnosis and prediction of CCA, and more attention should be given to the roles and mechanisms of circRNAs in CCA. In this review, we summarize the abnormal expression of circRNAs in CCA and the specific inflammatory microenvironment involved, as well as the roles and mechanisms of circRNAs in the occurrence and development of CCA. We also review the latest knowle dge on circRNAs in CCA and discuss the challenges associated with the introduction of circRNAs into clinical practice and their potential clinical value.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , Humanos , RNA Circular/genética , Colangiocarcinoma/patologia , MicroRNAs/genética , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Microambiente Tumoral/genética
3.
Gene ; 851: 147017, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36341726

RESUMO

Residual feed intake (RFI) is crucial economic indicator used for calculating the feed efficiency of growing beef cattle. circRNA plays an important biological role in gene transcriptional regulation, but little is known about its potential functional regulation underlying RFI phenotypic variation. As the core center of regulation of animal feeding, the hypothalamus is closely associated with RFI. Therefore, the present study aimed to identify the key genes and functional pathways contributing to variance in cattle RFI phenotypes using RNA sequencing from hypothalamic tissue samples, in order to gain insight into the potential regulatory role of circRNAs in bovine RFI phenotypic variation. Differentially expressed genes were detected by RNA sequencing for beef cattle in the high and low RFI groups, followed by GO, KEGG enrichment, and circRNA-miRNA co-expression network analysis. A total of 257 circRNAs were differentially expressed between the two groups, with 128 significantly upregulated and 129 significantly downregulated genes in H group compared to L group. Among them, 9 unique circRNAs were present in group L and 4 unique circRNAs were present in group H. GO and KEGG enrichment analysis of the source genes of the differentially expressed circRNAs revealed that they were mainly involved in metabolic processes, such as cellular metabolic processes, cellular macromolecular metabolic processes, and regulatory pathways related to nutrient metabolism, including protein and amino acid metabolism, as well as vitamin metabolism and pancreatic secretion associated with the animal feeding behavior. The circRNAs detected in this study were mostly novel, and have not been investigated directly to be associated with the RFI phenotype. Interestingly, most miRNAs of differentially expressed circRNAs predicted based on the circRNA-miRNA co-expression network analysis by using top 50 differentially expressed circRNAs and 13 unique circRNAs, have been reported to be related to animal RFIs, implying that circRNAs in bovine hypothalamic tissue may regulate phenotypic variation in RFI through miRNAs. The study results illustrate the complex biological functions of the hypothalamus in regulating feed efficiency and showing the potential role of circRNAs in the feeding behavior regulation of livestock, which would contributing to expanding the understanding of circRNA.


Assuntos
MicroRNAs , RNA Circular , Bovinos/genética , Animais , RNA Circular/genética , Ingestão de Alimentos/genética , Ração Animal/análise , Hipotálamo , MicroRNAs/genética
4.
J Environ Sci (China) ; 124: 451-461, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182153

RESUMO

Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of ≤ 2.5 µm (PM2.5), and a critical trigger of most PM2.5 exposure-associated diseases. However, the key molecular events regulating the PM2.5-induced airway inflammation are yet to be elucidated. Considering the critical role of circular RNAs (circRNAs) in regulating inflammation, we predicted 11 circRNAs that may be involved in the PM2.5-induced airway inflammation using three previously reported miRNAs through the starBase website. A novel circRNA circ_0008553 was identified to be responsible for the PM2.5-activated inflammatory response in human bronchial epithelial cells (16HBE) via inducing oxidative stress. Using a combinatorial model PM2.5 library, we found that the synergistic effect of the insoluble core and loaded Zn2+ ions at environmentally relevant concentrations was the major contributor to the upregulation of circ_0008553 and subsequent induction of oxidative stress and inflammation in response to PM2.5 exposures. Our findings provided new insight into the intervention of PM2.5-induced adverse outcomes.


Assuntos
MicroRNAs , RNA Circular , Células Epiteliais/metabolismo , Humanos , Inflamação/induzido quimicamente , MicroRNAs/metabolismo , Estresse Oxidativo , Material Particulado/toxicidade , Zinco/toxicidade
5.
Methods Mol Biol ; 2570: 223-234, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36156786

RESUMO

RNA aptamers can be genetically encoded in cells to probe and manipulate cellular function. The usefulness of aptamers in mammalian cells is limited by low accumulation and degradation by ribonucleases. Expression of circular RNA aptamers using the Tornado expression system achieves high stability and an abundance of intracellular RNA aptamers. With this method, RNA aptamers with otherwise minimal activity become potent inhibitors. Here, we describe protocols to characterize circular RNA aptamers expressed using Tornado. Included are methods to assess stability, abundance, subcellular localization, and target binding by circular RNA aptamers.


Assuntos
Aptâmeros de Nucleotídeos , Animais , Aptâmeros de Nucleotídeos/química , Mamíferos/genética , RNA/química , RNA Circular , Ribonucleases/metabolismo
6.
Cancer Lett ; 552: 215978, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36283584

RESUMO

Aberrant glucose metabolism is one of the most striking characteristics of metabolic reprogramming in cancer. Thus, clarifying the regulatory mechanism of glucose metabolism is crucial to understanding tumor progression and developing novel therapeutic strategies for cancer patients. Recent developments in circular RNAs have explained the regulatory mechanism of glucose metabolism from a new dimension. In this review, we briefly summarize the recent advances in circRNA research on cancer glucose metabolism and emphasize the different regulatory mechanisms, including acting as miRNA sponges, interacting with proteins and being translated into proteins. Additionally, we discuss the future research directions of circular RNAs in the field of glucose metabolism.


Assuntos
MicroRNAs , Neoplasias , Humanos , RNA Circular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Neoplasias/patologia , Glucose
7.
Life Sci Alliance ; 6(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36414375

RESUMO

Sry on the Y chromosome is the master switch of sex determination in mammals. It has been well established that Sry encodes a transcription factor that is transiently expressed in somatic cells of the male gonad, leading to the formation of testes. In the testis of adult mice, Sry is expressed as a circular RNA (circRNA) transcript. However, the physiological function of Sry circRNA (circSRY) remains unknown since its discovery in 1993. Here we show that circSRY is mainly expressed in the spermatocytes, but not in mature sperm or somatic cells of the testis. Loss of circSRY led to germ cell apoptosis and the reduction of sperm count in the epididymis. The level of γH2AX was decreased, and failure of XY body formation was noted in circSRY KO germ cells. Further study demonstrated that circSRY directly bound to miR-138-5p in spermatocytes, and in vitro assay suggested that circSRY regulates H2AX mRNA through sponging miR-138-5p. Our study demonstrates that, besides determining sex, Sry also plays an important role in spermatogenesis as a circRNA.


Assuntos
MicroRNAs , RNA Circular , Masculino , Camundongos , Animais , Proteína da Região Y Determinante do Sexo/genética , RNA Circular/genética , Sêmen , Espermatogênese/genética , Células Germinativas , MicroRNAs/genética , Mamíferos/genética
8.
Oncol Rep ; 49(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36416347

RESUMO

Tumors are one of the most common fatal diseases worldwide and pose a severe threat to human health. Effective tumor prevention and treatment strategies are persistent challenges in the medical community. Angiogenesis plays a critical role in and is the basis for tumor development and metastasis. Circular RNAs (circRNAs) are novel single­stranded covalently closed RNA molecules that are widely expressed in tumors due to their structural specificity and conservation. circRNAs affect angiogenesis by functioning as microRNA sponges to regulate vascular endothelial growth factor­related pathways, thereby participating in various stages of tumor growth, invasion and proliferation. The present review summarizes the involvement of circRNAs in the regulation of tumor angiogenesis through competing endogenous RNA mechanisms, with a particular focus on the regulatory role of circRNAs in tumor angiogenesis in various systems. It is considered that circRNAs have great potential for use as tumor diagnostic markers and anti­angiogenic therapies, and are thus worthy of further research and exploration.


Assuntos
MicroRNAs , Neoplasias , Humanos , RNA Circular/genética , Fator A de Crescimento do Endotélio Vascular , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Biomarcadores Tumorais
9.
Life Sci Alliance ; 6(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36302650

RESUMO

To understand the pathogenesis of acute lung injury (ALI), we focused on circEXOC5, a significantly up-regulated circular RNA in ALI. Using the in vivo cecal ligation and puncture (CLP)-induced ALI mouse model and in vitro LPS-challenged mouse pulmonary microvascular endothelial cell (MPVEC) model, we examined the impacts of knockdown circEXOC5 on lung injury, inflammation, and autophagy. The regulation between circEXOC5, polypyrimidine tract-binding protein 1 (PTBP1), S-phase kinase-associated protein 2 (Skp2), and Runt-related transcription factor 2 (Runx2) was investigated by combining RNA immunoprecipitation, qRT-PCR, mRNA stability, and ubiquitination assays. The significance of PTBP1 in circEXOC5-induced ALI phenotypes was examined both in vitro and in vivo. circEXOC5 was up-regulated and associated with increased inflammation and activated autophagy in cecal ligation and puncture-induced ALI lung tissues and LPS-challenged MPVECs. Through the interaction with PTBP1, circEXOC5 accelerated Skp2 mRNA decay, an E3 ubiquitin ligase for Runx2, and therefore increased Runx2 expression. Functionally, overexpressing PTBP1 reversed shcircEXOC5-inhibited ALI, inflammation, or autophagy. The signaling cascade circEXOC5/PTBP1/Skp2/Runx2, by essentially regulating inflammation and autophagy in MPVECs, aggravates sepsis-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Subunidade alfa 1 de Fator de Ligação ao Core , Ribonucleoproteínas Nucleares Heterogêneas , Proteína de Ligação a Regiões Ricas em Polipirimidinas , RNA Circular , Proteínas Quinases Associadas a Fase S , Animais , Camundongos , Lesão Pulmonar Aguda/genética , Autofagia/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Ribonucleoproteínas Nucleares Heterogêneas/genética , Inflamação/genética , Lipopolissacarídeos , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteínas Quinases Associadas a Fase S/genética , RNA Circular/genética
10.
Gene ; 851: 146950, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36228866

RESUMO

Circular RNA (circRNA) is a neoteric researched transcript that involves gene regulation by serving as a micro-RNA (miRNA) sponge. This circRNA-miRNA-mRNA interaction is being recently explored, and its dysregulation is associated with disease pathogenesis and progression. Studies have demonstrated the involvement of this regulatory network in endothelium dysfunction-mediated regulation of pathology in vascular diseases. The disturbances or imbalance of vasodilation and vasoconstriction factors due to changes in oxidative stress, inflammatory markers, and nitric oxide signaling leads to endothelial dysfunction. These disturbances cause impermeability of blood through the endothelial barrier, thus developing atherosclerotic lesions. Advancements in high-throughput techniques like genome and RNA sequencing have made us understand this complex regulatory network causing endothelial dysfunction. In this review, we emphasize the network of interactions between circRNA, miRNA, and mRNA that mediates gene regulation and is linked to endothelial dysfunction in various pathological conditions.


Assuntos
MicroRNAs , Doenças Vasculares , Humanos , RNA Circular/genética , MicroRNAs/genética , RNA Mensageiro/genética , Redes Reguladoras de Genes , Doenças Vasculares/genética
12.
Front Immunol ; 13: 910860, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36458003

RESUMO

Avian coccidiosis is a common enzootic disease caused by infection of Eimeria species parasites. It causes huge economic losses in the global poultry industry. Current control using anticoccidial drugs or vaccination is limited due to drug resistance and the relatively high cost of vaccines. Improving host genetic resistance to Eimeria species is considered an effective strategy for improved control of coccidiosis. Circular RNAs (circRNAs) have been found to function as biomarkers or diagnoses of various kinds of diseases. The molecular biological functions of circRNAs, miRNAs, and mRNAs related to Sasso chicken have not yet been described during Eimeria species challenge. In this study, RNA-seq was used to profile the expression pattern of circRNAs, miRNAs, and mRNAs in spleens from Eimeria tenella-infected and non-infected commercial dual-purpose Sasso T445 breed chickens. Results showed a total of 40 differentially expressed circRNAs (DEcircRNAs), 31 differentially expressed miRNAs (DEmiRNAs), and 820 differentially expressed genes (DEmRNAs) between infected and non-infected chickens. Regulatory networks were constructed between differentially expressed circRNAs, miRNAs, and mRNAs to offer insights into the interaction mechanisms between chickens and Eimeria spp. Functional validation of a significantly differentially expressed circRNA, circMGAT5, revealed that circMGAT5 could sponge miR-132c-5p to promote the expression of the miR-132c-5p target gene monocyte to macrophage differentiation-associated (MMD) during the infection of E. tenella sporozoites or LPS stimulation. Pathologically, knockdown of circMGAT5 significantly upregulated the expression of macrophage surface markers and the macrophage activation marker, F4/80 and MHC-II, which indicated that circMGAT5 might inhibit the activation of macrophage. miR-132c-5p markedly facilitated the expression of F4/80 and MHC-II while circMGAT5 could attenuate the increase of F4/80 and MHC-II induced by miR-132c-5p, indicating that circMGAT5 exhibited function through the circMGAT5-miR-132c-5p-MMD axis. Together, our results indicate that circRNAs exhibit their resistance or susceptive roles during E. tenella infection. Among these, circMGAT5 may inhibit the activation of macrophages through the circMGAT5-miR-132c-5p-MMD axis to participate in the immune response induced by Eimeria infection.


Assuntos
Coccidiose , Eimeria , MicroRNAs , Animais , RNA Circular/genética , RNA Mensageiro/genética , MicroRNAs/genética , Galinhas/genética , Perfilação da Expressão Gênica , Coccidiose/genética , Coccidiose/veterinária
13.
Med Oncol ; 40(1): 24, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454423

RESUMO

As one of the most common malignant cancers in the world, gastric cancer is caused by mang factors among which tobacco smoke is an important risk factor. Gastric cancer stem cells (GCSCs) and the derived exosomes play a key role in the occurrence and development of gastric cancer, and exosomal circRNA is considered as a new regulatory factor in the development of gastric cancer. However, it is unclear whether tobacco smoke can affect exosomes and their transport circRNAs to promote the development of gastric cancer. Herein, we provided a new insight into tobacco smoke promoting the progression of gastric cancer. In the present study, we demonstrated that tobacco smoke-induced exosomes promoted the spheroidizing ability, stemness genes expression, and epithelial-mesenchymal transition (EMT) process of GCSCs. We further found that hsa-circRNA-000670 (circ670) was up-regulated in tissues of gastric cancer patients with smoking history, tobacco smoke-induced GCSCs, and their exosomes. Functional assays have shown that circ670 knockdown inhibited the stemness and EMT process of GCSCs, whereas circ670 overexpression appeared to have an opposite effect. Our findings indicated that exosomal circ670 promotes the development of tobacco smoke-induced gastric cancer, which may provide insight into the mechanism of tobacco smoke promoting the progression of gastric cancer.


Assuntos
Exossomos , Neoplasias Gástricas , Poluição por Fumaça de Tabaco , Humanos , RNA Circular/genética , Neoplasias Gástricas/genética , Tabaco/efeitos adversos , Células-Tronco Neoplásicas
14.
BMC Genomics ; 23(1): 790, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456907

RESUMO

BACKGROUND: Excessive deposition of abdominal fat poses serious problems in broilers owing to rapid growth. Recently, the evolution of the existing knowledge on long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have established their indispensable roles in multiple physiological metabolic processes, including adipogenesis and fat deposition. However, not much has been explored on their profiles in the abdominal fat tissues of broilers to date. In the study, we aimed to characterize the vital candidates of lncRNAs and circRNAs and their underlying regulations for abdominal fat deposition in broilers. RESULTS: The present study sequenced the lncRNAs and circRNAs expression profiles in the abdominal fat tissues isolated from 7-week-old broilers, who were divergently selected for their fatness. It identified a total of 3359 lncRNAs and 176 circRNAs, demonstrating differential expressed (DE) 30 lncRNAs and 17 circRNAs between the fat- and lean-line broilers (|log2FC| ≥ 1, P < 0.05). Subsequently, the 20 cis-targets and 48 trans-targets of the candidate DE lncRNAs were identified for depositing abdominal fat by adjacent gene analysis and co-expression analysis, respectively. In addition, the functional enrichment analysis showed the DE lncRNAs targets and DE circRNAs host genes to be mainly involved in the cellular processes, amino/fatty acid metabolism, and immune inflammation-related pathways and GO terms. Finally, the vital 16 DE lncRNAs located in cytoplasm and specifically expressed in fat/lean line and their targets were used to construct the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) regulatory network, comprising 7 DE lncRNAs, 28 miRNAs, 11 DE mRNAs. Notably, three lncRNAs including XR_001468036.2, XR_003077610.1 and XR_001466431.2 with the most connected degrees might play hub regulatory roles in abdominal fat deposition of broilers. CONCLUSIONS: This study characterized the whole expression difference of lncRNAs and circRNAs between the two lines broilers with divergently ability of abdominal fat. The vital candidate DE lncRNAs/circRNAs and ceRNA regulations were identified related to the deposition of abdominal fat in chicken. These results might further improve our understanding of regulating the non-coding RNAs in obesity.


Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , RNA Circular/genética , RNA Longo não Codificante/genética , Galinhas/genética , Gordura Abdominal , Antígenos CD36 , MicroRNAs/genética , RNA Mensageiro
15.
Front Cell Infect Microbiol ; 12: 980974, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452301

RESUMO

Circular RNA (circRNA) exists extensively and plays essential roles in serving as microRNA (miRNA) or protein sponges and protein scaffolding in many organisms. However, the profiles and potential functions of the virus-encoded circRNA, including human cytomegalovirus (HCMV)-encoded circular RNAs, remain unclear. In the present study, HCMV-encoded circRNAs profile in human embryonic lung fibroblasts (HELF) with lytic infection was investigated using RNA deep sequencing and bioinformatics analysis. In total, 629 HCMV-encoded circRNAs were identified with various expression patterns in our results. The full sequences and alternative splicings of circUS12, circUL55, and circUL89 were verified by reverse transcriptase-PCR (RT-PCR) with divergent primers followed and Sanger sequencing. Transcription of circUL89 was validated by Northern blot. The HCMV-encoded circRNA-miRNA network analyses revealed the potential function of HCMV-encoded circRNAs during HCMV infection in HELFs. Collectively, HCMV infection deduced abundant HCMV-associated circRNAs during infection, and the HCMV-encoded circRNAs might play important roles in benefiting HCMV infection.


Assuntos
MicroRNAs , RNA Circular , Humanos , RNA Circular/genética , Citomegalovirus/genética , MicroRNAs/genética , Análise de Sequência de RNA , Processamento Alternativo , RNA Viral/genética
16.
Front Endocrinol (Lausanne) ; 13: 1028031, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440224

RESUMO

Background: Osteosarcoma is a common bone sarcoma that occurs in childhood and adolescence. Although research on non-coding RNAs (ncRNAs) of osteosarcoma has been developed rapidly in recent years, a specific bibliometric analysis on this topic has not yet been performed. The bibliometric analysis aims to summarize knowledge atlas, research hotspots, and emerging trends and to provide researchers with new perspectives in further studies. Methods: All publications regarding ncRNAs of osteosarcoma published from 2000 to 2021 were retrieved from the Web of Science Core Collection. Quantitative indicators including the number of publications and citations, H-index, and journal citation reports were analyzed by using Excel 2019 and R software. VOSviewer and CiteSpace were used to analyze the cooperation among countries/institutions/journals/authors and the co-occurrence of keywords, keywords bursts, and references. Results: A total of 3206 publications were extracted. A significant growth trend in the annual number of publications over the past 22 years is revealed (R 2 = 0.999). The most prolific country and institution were China (2260) and Shanghai Jiao Tong University (134), respectively. Professors Wang W and Liu W contributed the most to this field. The keywords were stratified into six clusters: Cluster 1 (apoptosis and growth), Cluster 2 (cancer and progression), Cluster 3 (microRNAs and downregulation), Cluster 4 (genes and differentiation), Cluster 5 (expression and biological functions), and Cluster 6 (metastasis). The long non-coding RNAs and circular RNAs have been considered as an important research hotspot in the near future. Conclusion: This study offers a scientific perspective on ncRNAs of osteosarcoma and provides researchers with valuable information to understand the knowledge structure and to identify emerging trends in this field.


Assuntos
Bibliometria , Osteossarcoma , Humanos , China , Publicações , RNA Circular , Osteossarcoma/genética
17.
Braz J Med Biol Res ; 55: e12347, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36350973

RESUMO

Severe pneumonia related to human adenoviruses (HAdVs) has a high lethality rate in children and its early diagnosis and treatment remain a major challenge. Circular RNAs (circRNAs) are novel long noncoding RNAs that play important roles in gene regulation and disease pathogenesis. To investigate the roles of circRNAs in HAdV pneumonia, we analyzed the circRNA profiles of healthy children and children with HAdV pneumonia, including both mild and severe cases, and identified 139 significantly upregulated circRNAs in children with HAdV pneumonia vs healthy controls and 18 significantly upregulated circRNAs in children with severe HAdV pneumonia vs mild HAdV pneumonia. In particular, hsa_circ_0002171 was differentially expressed in both groups and might thus be useful as a diagnostic biomarker of HAdV pneumonia and severe HAdV pneumonia. To identify the underlying mechanisms of circRNAs in HAdV pneumonia, we analyzed the transcriptome of children with HAdV pneumonia and established a circRNA-mRNA regulatory network. Enrichment analysis of differentially expressed target mRNAs demonstrated that the differentially expressed genes between healthy controls and HAdV pneumonia patients were mainly involved in RNA splicing while the differentially expressed genes between children with mild and severe HAdV pneumonia were mainly involved in regulating lymphocyte activation. Receiver operating characteristic (ROC) curve analysis suggested that hsa_circ_0002171 had a significant value in the diagnosis of HAdV pneumonia and of severe HAdV pneumonia. Taken together, the circRNA expression profile was altered in children with HAdV pneumonia. These results demonstrated that hsa_circ_0002171 is a potential diagnostic biomarker of HAdV pneumonia.


Assuntos
Adenovírus Humanos , Pneumonia , Criança , Humanos , RNA Circular/genética , Adenovírus Humanos/genética , Adenovírus Humanos/metabolismo , Biomarcadores , Curva ROC , RNA Mensageiro/genética , RNA/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-36374958

RESUMO

Inactivation of hepatic stellate cells (HSCs) slows down liver cirrhosis (LC) advancement. The role of circular RNAs (circRNAs) in LC is largely undiscovered. Here, we clarified the effect of circCHD2 on HSCs. LX-2 cells were stimulated with TGF-ß1 to establish a cell model. The circCHD2, miR-200b-3p, and HLF were inspected using quantitative real-time PCR (qPCR). Cell counting kit-8, 5-Ethynyl-2'-deoxyuridine, together with colony formation assays were all conducted to analyze cell proliferation. α-SMA and Col1A1 were evaluated by qPCR and Western blot. The targets of circCHD2 and miR-200b-3p were verified by luciferase reporter assay. We found the circCHD2 was upregulated in the patients with LC and transforming growth factor beta 1 (TGF-ß1)-stimulated LX-2 cells. Interfering of circCHD2 inhibited the proliferation induced by TGF-ß1, downregulated α-SMA, and Col1A1. CircCHD2 served as a miR-200b-3p sponge, which directly targeted downstream HLF. Downregulated miR-200b-3p abrogated suppression on the cellular process, α-SMA and Col1A1 levels induced by knockdown of circCHD2. Enforced HLF reversed the effect induced by miR-200b-3p overexpression. Taken together, a loss of circCHD2/miR-200b-3p/HLF axis contributed to alleviate LC progression. The findings suggested that circCHD2 may have potential to be a therapeutic target of LC.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica , Cirrose Hepática , MicroRNAs , RNA Circular , Humanos , Proliferação de Células/genética , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática/genética , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , MicroRNAs/genética , Fator de Crescimento Transformador beta1/farmacologia , RNA Circular/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética
19.
Brief Bioinform ; 23(6)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36384071

RESUMO

Emerging evidence suggests that circular RNA (circRNA) is an important regulator of a variety of pathological processes and serves as a promising biomarker for many complex human diseases. Nevertheless, there are relatively few known circRNA-disease associations, and uncovering new circRNA-disease associations by wet-lab methods is time consuming and costly. Considering the limitations of existing computational methods, we propose a novel approach named MNMDCDA, which combines high-order graph convolutional networks (high-order GCNs) and deep neural networks to infer associations between circRNAs and diseases. Firstly, we computed different biological attribute information of circRNA and disease separately and used them to construct multiple multi-source similarity networks. Then, we used the high-order GCN algorithm to learn feature embedding representations with high-order mixed neighborhood information of circRNA and disease from the constructed multi-source similarity networks, respectively. Finally, the deep neural network classifier was implemented to predict associations of circRNAs with diseases. The MNMDCDA model obtained AUC scores of 95.16%, 94.53%, 89.80% and 91.83% on four benchmark datasets, i.e., CircR2Disease, CircAtlas v2.0, Circ2Disease and CircRNADisease, respectively, using the 5-fold cross-validation approach. Furthermore, 25 of the top 30 circRNA-disease pairs with the best scores of MNMDCDA in the case study were validated by recent literature. Numerous experimental results indicate that MNMDCDA can be used as an effective computational tool to predict circRNA-disease associations and can provide the most promising candidates for biological experiments.


Assuntos
Redes Neurais de Computação , RNA Circular , Humanos , Algoritmos
20.
Genes (Basel) ; 13(11)2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36360223

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are a novel class of epigenetic regulators that participate in leukemogenesis. However, their roles in leukemia relapse after transplantation remain unclear. METHODS: We defined the circRNAs profile of the bone-marrow-enriched CD34+ cells from ten acute myeloid leukemia (AML) patients after transplantation (five relapse [RE] and five continuous complete remission [CR]) and four healthy controls (HCs) by RNA-seq. Differentially expressed circRNAs were validated using real-time quantitative polymerase chain reaction (RT-qPCR) in an independent cohort of six AML patients with pairwise samples at diagnosis and at relapse and six controls. RESULTS: The bioinformatics analysis revealed a distinct circRNAs profile in relapse patients compared with controls (CR or HCs), while there was no significant difference between CR and HCs. Functional enrichment analysis demonstrated that mRNAs co-expressed with identified circRNAs were primarily involved in immune-related pathways, including the T cell receptor signaling pathway and lymphocyte differentiation. Moreover, we performed a protein-protein interaction network based on the immune-related genes and annotated 20 hub genes. The abnormal expression of hub genes was responsible for impairing T cell co-stimulation and activation, thus contributing to the immune escape of relapse blasts. We further constructed competing endogenous RNAs (ceRNA) regulatory networks based on immune-related genes and identified 10 key circRNAs that are associated with immune evasion. Six candidate circRNAs and their associated miRNA/mRNAs in the ceRNA network were randomly selected to be validated in another set by RT-qPCR. CONCLUSIONS: CircRNAs dysregulation may be involved in the immune evasion of relapse blasts and is associated with AML relapse. Our results identify several promising biomarkers and might provide novel insights into the biology of AML relapse post-transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , MicroRNAs , Humanos , RNA Circular/genética , Evasão da Resposta Imune , RNA Mensageiro/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Recidiva
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