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1.
Chemosphere ; 286(Pt 1): 131614, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34325257

RESUMO

Particulate matter (PM)-induced airway inflammation contributes to the development and exacerbation of chronic airway diseases. Circular RNA (circRNA) is a new class of non-coding RNA that participates in gene regulation in various respiratory diseases, but the regulatory role of circRNA in PM-induced airway inflammation has not been fully elucidated. In this study, we performed the human circRNA microarray to reveal differentially expressed circRNAs in PM-induced human bronchial epithelial cells (HBECs). A total of 176 upregulated and 15 downregulated circRNAs were identified. Of these, a new circRNA termed circTXNRD1 was upregulated by PM exposure in a dose- and time-dependent manner. Knockdown of circTXNRD1 significantly attenuated PM-induced expression of proinflammatory cytokine interleukin 6 (IL-6). CircRNA pull-down, dual-luciferase reporter assay and fluorescence in situ hybridization showed that circTXNRD1 acted as an endogenous sponge to decrease miR-892a levels in HBECs. Downregulation of miR-892a could increase cyclooxygenase-2 (COX-2) expression and eventually promote IL-6 secretion in PM-induced HBECs. Taken together, our findings reveal circTXNRD1 as a novel inflammatory mediator in PM-induced inflammation in HBECs via regulating miR-892a/COX-2 axis. These results provide new insight into the biological mechanism underlying PM-induced inflammation in chronic airway diseases.


Assuntos
MicroRNAs , RNA Circular , Ciclo-Oxigenase 2/genética , Células Epiteliais , Humanos , Hibridização in Situ Fluorescente , Inflamação/induzido quimicamente , Inflamação/genética , MicroRNAs/genética , Material Particulado/toxicidade , RNA/genética
2.
Environ Pollut ; 292(Pt A): 118332, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637826

RESUMO

With the continued increase of global ammonia emission, the damage to human or animal caused by ammonia pollution has attracted wide attention. The noncoding RNAs have been reported to regulate a variety of biological processes under different environmental stimulation via ceRNA (competing endogenous RNA) networks. Autophagy is a hallmark of tissue damage from air pollution. However, the specific role of circular RNAs (circRNAs) in the injury of intestinal tissue caused by autophagy remains unclear. Here, we established 42-days old ammonia-exposed broiler models and observed that autophagy flux in broiler jejunum was activated under ammonia exposure. Meanwhile, a total of eight significantly dysregulated expressed circRNAs were obtained and a circRNAs-miRNAs-genes interaction networks were constructed by bioinformatics analysis. Furthermore, an axis named circRNA-IGLL1/miR-15a/RNF43 was predicted to participate in the excessive autophagy by targeting RNF43. The target relationship was proved by dual-luciferase reporter assay in vitro. Mechanistically, downregulated circRNA-IGLL1 could suppress the expression of RNF43 in ammonia-exposed jejunum and the Wnt/ß-catenin pathway was activated. Inhibition of miR-15a reversed autophagy caused by downregulated circRNA-IGLL1. CircRNA-IGLL1 could competitively bind miR-15a to regulate RNF43 expression, thus modulating the occurrence of autophagy. Taken together, our results showed that circRNA-IGLL1/miR-15a/RNF43 axis is involved in ammonia-induced intestinal autophagy in broilers.


Assuntos
MicroRNAs , RNA Circular , Amônia/toxicidade , Animais , Autofagia , Galinhas , Humanos , Jejuno , MicroRNAs/genética , Ubiquitina-Proteína Ligases , beta Catenina
3.
Anal Chim Acta ; 1189: 339210, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815051

RESUMO

Circular Ribonucleic Acid (CircRNA) plays regulatory roles in many biological processes, such as tumors and metabolic diseases. Due to the fact that circRNA is more stable and conservative than linear RNA, circRNA has become a potential biomarker in early clinical diagnosis and biomedical research. Therefore, the quantification of circRNA expression level is of importance for understanding their functions and their applications for disease diagnosis and treatment. Nevertheless, due to the low abundance of circRNA, it is still a challenge for the analysis of circRNA in cells. Herein, we proposed a sensitive detection method for circRNA based on the T7 exonuclease-assisted cycling enzymatic amplification. The fluorescent sensor was constructed by a hairpin molecular beacon and T7 exonuclease. With the cycling enzymatic amplification process, this sensor achieved the limit of detection of 1 pM with a good linear correlation in the range of 0-100 pM (R2 = 0.9891) using circBART2.2 as a model. Furthermore, we applied the proposed method in the determination of circBART2.2 in cell lysates. The results demonstrated that this method has promising applications in early diagnosis of Epstein-Barr virus (EBV) infection-related diseases using circRNA as the biomarker.


Assuntos
Infecções por Vírus Epstein-Barr , RNA Circular , Contagem de Células , Herpesvirus Humano 4 , Humanos , Limite de Detecção , Espectrometria de Fluorescência
4.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(11): 1130-1138, 2021 Nov 24.
Artigo em Chinês | MEDLINE | ID: mdl-34775724

RESUMO

Objective: To explore the differential expression of circRNAs and their potential impact on the pathophysiological process in cardiac hypertrophy. Methods: Six SPF C57BL/6J male mice, aged 8 to 10 weeks, were randomly divided into transverse aortic constriction (TAC) group (n=3) or sham operation(sham) group (n=3) according to random number table method. TAC mouse model was used to induce cardiac hypertrophy. Four weeks after surgery, high-throughput sequencing analysis was performed to detect differentially expressed circRNA in left myocardial tissues of mice between TAC group and sham group, and principal component analysis of circRNA was performed by R language software. Enrichment analysis was performed by GO and KEGG databases to predict the basic functions of differentially expressed circRNA-derived genes and their biological pathways. The differentially expressed circRNAs in the sequencing results were verified by real-time fluorescence quantitative polymerase chain reaction. Cytoscape software was used to construct circRNA-microRNA (miRNA) network maps to predict their interactions by combining differentially expressed circRNA and TargetScan predicted miRNA sites. Results: Principal component analysis was performed on 4 580 circRNAs detected from 6 samples of mice in TAC group and sham group. The results of R language software indicated that the variance contribution rate of the first 3 principal components, namely the first, second and third principal components, was 91.01%, 3.19% and 2.01%, respectively, and the cumulative variance contribution rate of the 3 components was 96.21%. Among the differentially expressed circRNAs, 6 (19%) were up-regulated and 25 (81%) were down-regulated in the TAC group. GO analysis showed that differentially expressed circRNA was closely related to the occurrence and development of cardiac hypertrophy, and KEGG pathway analysis suggested that downregulated circRNA expression was involved in the regulation of actin cytoskeleton. Fifteen out of the 31 differentially expressed circRNAs were selected for real-time fluorescence quantitative polymerase chain reaction verification, and the results showed that 8 circRNAs were consistent with sequencing results. circRNA-miRNA co-expression network analysis results showed that chr11:65218529-65233184-interacts with mmu-miRNA-30e-3p and mmu-miRNA-30a-3p. Conclusions The differential expression of circRNA in hypertrophic myocardium mice is evidenced in TAC mouse model. circRNA may interact with the corresponding miRNA to influence the occurrence and development of cardiac hypertrophy through autophagy-related cellular hypertrophy pathway or apoptosis-related pathological phenotypes.


Assuntos
MicroRNAs , RNA Circular , Animais , Biologia Computacional , Hipertrofia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Miocárdio
5.
Hematology ; 26(1): 885-895, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34753401

RESUMO

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a highly proliferative hematologic malignancy. Circular RNA hsa_circ_0000745 (circ_0000745) has been reported as an oncogene in acute lymphoblastic leukemia (ALL). However, whether circ_0000745 can drive T-ALL progression by controlling notch receptor 1 (NOTCH1) expression is unclear. METHODS: Relative expression of circ_0000745 and NOTCH1 in bone marrow (BM) samples and T-ALL cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Loss- and gain-of-function experiments were executed to evaluate the effects of circ_0000745 and NOTCH1 on T-ALL cell proliferation and apoptosis. The microRNAs (miRs) that might jointly interact with circ_0000745 and NOTCH1 were predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Circ_0000745 and NOTCH1 were overexpressed in T-ALL BM and T-ALL cells. Functionally, both circ_0000745 and NOTCH1 overexpression promoted T-ALL cell proliferation and curbed T-ALL cell apoptosis. In contrast, both circ_0000745 and NOTCH1 silencing restrained T-ALL cell proliferation and induced T-ALL cell apoptosis. Furthermore, circ_0000745 could control T-ALL cell proliferation and apoptosis through regulating NOTCH1 expression. Importantly, circ_0000745 regulated NOTCH1 expression by sponging miR-193b-3p. CONCLUSION: Our findings proposed a novel model in which circ_0000745 promoted cell proliferation and curbed cell apoptosis via upregulating NOTCH1 through serving as a miR-193b-3p sponge in T-ALL.


Assuntos
Regulação Leucêmica da Expressão Gênica , MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , RNA Circular/genética , Receptor Notch1/genética , Apoptose , Proliferação de Células , Células Cultivadas , Criança , Feminino , Humanos , Masculino , Regulação para Cima
6.
BMC Bioinformatics ; 22(1): 551, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772332

RESUMO

BACKGROUND: The existing studies show that circRNAs can be used as a biomarker of diseases and play a prominent role in the treatment and diagnosis of diseases. However, the relationships between the vast majority of circRNAs and diseases are still unclear, and more experiments are needed to study the mechanism of circRNAs. Nowadays, some scholars use the attributes between circRNAs and diseases to study and predict their associations. Nonetheless, most of the existing experimental methods use less information about the attributes of circRNAs, which has a certain impact on the accuracy of the final prediction results. On the other hand, some scholars also apply experimental methods to predict the associations between circRNAs and diseases. But such methods are usually expensive and time-consuming. Based on the above shortcomings, follow-up research is needed to propose a more efficient calculation-based method to predict the associations between circRNAs and diseases. RESULTS: In this study, a novel algorithm (method) is proposed, which is based on the Graph Convolutional Network (GCN) constructed with Random Walk with Restart (RWR) and Principal Component Analysis (PCA) to predict the associations between circRNAs and diseases (CRPGCN). In the construction of CRPGCN, the RWR algorithm is used to improve the similarity associations of the computed nodes with their neighbours. After that, the PCA method is used to dimensionality reduction and extract features, it makes the connection between circRNAs with higher similarity and diseases closer. Finally, The GCN algorithm is used to learn the features between circRNAs and diseases and calculate the final similarity scores, and the learning datas are constructed from the adjacency matrix, similarity matrix and feature matrix as a heterogeneous adjacency matrix and a heterogeneous feature matrix. CONCLUSIONS: After 2-fold cross-validation, 5-fold cross-validation and 10-fold cross-validation, the area under the ROC curve of the CRPGCN is 0.9490, 0.9720 and 0.9722, respectively. The CRPGCN method has a valuable effect in predict the associations between circRNAs and diseases.


Assuntos
Algoritmos , RNA Circular
7.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 56(11): 1098-1108, 2021 Nov 09.
Artigo em Chinês | MEDLINE | ID: mdl-34763405

RESUMO

Objective: To investigate the effects of circular RNA (circRNA) BICD2 (circ-BICD2) on glutamine metabolism, cell proliferation, migration, invasion and apoptosis of oral squamous cell carcinoma (OSCC) cells and to further explore the possible mechanism. Methods: OSCC cells were purchased from Shanghai Institute of Cellular Cells, Chinese Academy of Sciences. Samples of OSCC tissues and corresponding adjacent tissues were collected from 35 OSCC patients who underwent surgical resection at the First Affiliated Hospital of Zhengzhou University from January 2016 to January 2018. Real-time quantitative PCR (RT-qPCR) and western blot were performed to detect the expression levels of circ-BICD2, miR-296-5p and transgelin2 (TAGLN2) in OSCC tissues and cells. Bioinformatics, dual luciferase report experiment and RNA immunoprecipitation (RIP) experiment were used to determine the targeting relationship between circ-BICD2 and miR-296-5p, miR-296-5p and TAGLN2. According to different transfection oligonucleotides or plasmids, CAL27 and SCC9 cells were divided into si-NC group (transfection si-NC), si-circ-BICD2 group (transfection si-circ-BICD2), si-circ-BICD2+anti-miR-NC group (transfected with si-circ-BICD2 and anti-miR-NC), si-circ-BICD2+anti-miR-296-5p group (transfected with si-circ-BICD2 and anti-miR-296-5p), miR-NC group (transfected with miR-NC), miR-296-5p group (transfected with miR-296-5p mimic), miR-296-5p+pcDNA (transfected with miR-296-5p mimic and pcDNA) and miR-296-5p+TAGLN2 group (transfected with miR-296-5p mimic and pcDNA-TAGLN2). Cell counting kit 8(CCK-8), colony formation experiment, flow cytometry, Scratch healing test and Transwell experiment were applied to detect OSCC cell viability, number of colonies, cycle distribution, apoptosis rate, migration rate and invasive cell numbers. Glutamine (gln) consumption, α-ketoglutaric acid (α-KG) production and adenosine triphosphate (ATP) concentration were also detected by the kit. The expression of cyclinD1 and Glutamine hydrolase (GLS1) proteins of CAL27 and SCC9 cells in each of the groups were detected by western blot. Twelve four-week-old clean BALB/c female nude mice were injected with a single-cell suspension of SCC9 cells into the axillary skin to establish a transplanted tumor model. Twelve transplanted tumor model mice were divided into sh-circ-BICD2 group and sh-NC group. Mice were sacrificed by cervical dislocation at 32 days after injection, the tumors were removed and the tumor weight was tested. Results: The expressions of circ-BICD2 (2.54±0.74) and TAGLN2 (1.86±0.15) were increased (P<0.05), while the expression of MiR-296-5p was decreased in OSCC tissues (P<0.05). Cell viability, clone formation numbers, migration rate, invasive cell numbers, S phase cell ratio, glu consumption, α-KG production, ATP concentration, expression of cyclinD1 and GLS1 proteins of OSCC cells were significantly reduced after interference with circ-BICD2 expression. The apoptosis rate, the proportion of cells in G0-G1 phase and the expression of miR-296-5p were significantly increased (P<0.05). Inhibiting the expression of miR-296-5p coulld reverse the effect of interfering with circ-BICD2 on OSCC cell proliferation, migration, invasion, apoptosis and glutamine metabolism (P<0.05). After overexpression of miR-296-5p, cell viability, clone formation red number, migration rate, number of invasive cells, S phase cell ratio, glu consumption, α-KG production, ATP concentration and expressions of cyclinD1, GLS1 and TAGLN2 proteins in OSCC cells were significant decrease. The rate of apoptosis and the proportion of cells in G0-G1 phase were significantly increased (P<0.05). Compared with overexpression of miR-296-5p, cell viability, clone formation red number, migration rate, number of invasive cells, S phase cell ratio, glu consumption, α-KG production, ATP concentration, cyclinD1, GLS1 and TAGLN2 proteins in OSCC cells after overexpression of miR-296-5p and TAGLN2 were significantly increased, and the apoptosis rate and the proportion of cells in the G0-G1 phase were significantly decreased (P<0.05). Compared with the sh-NC group, the tumor weights of mice in the sh-circ-BICD2 group were significantly reduced (P<0.05). Conclusions: Circ-BICD2 was highly expressed in OSCC cells. Interfering with circ-BICD2 could inhibit the proliferation, migration and invasion of OSCC cells, glutamine metabolism and tumor growth and promote cell apoptosis, which might be relate to the regulation of miR-296-5p/TAGLN2 molecular axis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Animais , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , China , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos , Neoplasias Bucais/genética , RNA Circular , Carcinoma de Células Escamosas de Cabeça e Pescoço
8.
Clin Lab ; 67(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34758237

RESUMO

BACKGROUND: CircPVT1's effects and mechanisms of acute lymphoblastic leukemia were explored in this research. METHODS: Real-time fluorescent quantitative PCR was utilized to test circPVT1 and miR-125b in ALL samples and ALL cell systems. Dual luciferase reporter assay verified the combination of circPVT1 and miR-125b. We utilized circPVAT1 as well as miR-125b's over-expression and low-expression to prove their influence on cell proliferation and invading. RESULTS: We found that more expression of circPVT1 occurred in ALL samples and ALL cell systems. CircPVT1 over-expression promoted ALL cell proliferation and migration besides invading. CircPVT1 low expression inhibited ALL cell proliferation and migration besides invading. MiR-125b was a target combination of circPVT1. CircPVT1 was able to enhance NF-κB signal pathway's expression through reducing miR-125b. CONCLUSIONS: CircPVT2 can promote ALL cell proliferation and invading through miR-125b modulation of NF-κB, which would be one new potential target for ALL therapy.


Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proliferação de Células , Humanos , MicroRNAs/genética , NF-kappa B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , RNA Circular , Transdução de Sinais
9.
Braz J Med Biol Res ; 54(12): e11459, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34730679

RESUMO

Reportedly, circular RNAs (circRNAs) are crucial regulators in cancer progression. Nonetheless, the molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) has not been fully clarified. Gene expression omnibus (GEO) database was employed to screen out the differentially expressed circRNAs in HCC. qRT-PCR and western blot were executed to detect circ_0001806 expression, miR-193a-5p expression, and MMP16 mRNA and protein expressions in HCC. The effect of circ_0001806 on HCC was analyzed by the CCK-8 method and Transwell experiment. RIP assay, pull-down experiment, and dual-luciferase reporter gene experiment were applied to validate the targeting relationships among circ_0001806, miR-193a-5p, and MMP16. Circ_0001806 was up-modulated in HCC tissues and cell lines. Knockdown of circ_0001806 impeded the multiplication, migration, and invasion of HCC cells. Circ_0001806 could up-regulate MMP16 expression through repressing miR-193a-5p, thereby facilitating the malignant biological behaviors of HCC. Circ_0001806 promoted HCC progression by regulating miR-193a-5p/MMP16 axis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Neoplasias Hepáticas/genética , Metaloproteinase 16 da Matriz , MicroRNAs/genética , RNA Circular
10.
Yi Chuan ; 43(11): 1066-1077, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34815209

RESUMO

Castration can reduce odor and fights in boars, but the carcass yield is reduced, and the intramuscular fat content is increased. Understanding its molecular mechanism is of great significance for production. Recent studies have shown that circular RNAs (circRNAs) play an important role(s) in the regulation of muscle development. To explore the effects of circRNAs on the development of longissimus dorsi (LD) muscle after castration, six Huainan male pigs were selected and three of which were randomly castrated. Six pigs were slaughtered when their body weight reached around 130 kg, and the LD muscle samples were collected. The differentially expressed circRNAs (DECs) were screened by high-throughput sequencing and functionally analyzed using the KEGG databases. DECs-miRNAs network was constructed, and the expression profiles of candidate circRNAs and their interactions with miRNAs were verified in porcine skeletal muscle satellite cells. The results showed that a total of 5866 circRNAs were obtained, and 370 DECs were identified in LD muscle between the castrated and intact groups (| log2Foldchange | > 1, padj <0.8). KEGG enrichment indicated that the parental genes for the DECs were mainly enriched in the pathways associated with muscle development, muscle fiber type transformation, and energy metabolism. There were 8 miRNAs and 69 circRNAs enriched in the DECs-miRNA network. circRNA_2241 and circRNA_4237 were selected for verification, which showed that these two circRNAs really existed and their expression profiles were consistent with the sequencing results. Further, preliminary analysis showed that circRNA_2241 interacted with miR-1, and testosterone promoted circRNA_2241 but inhibited miR-1 expression. These results confirmed that circRNAs might participate in the regulation of LD muscle development after castration by interacting with miRNAs, thereby providing new materials and references for analyses on the molecular mechanisms of castration on the regulation of muscle development.


Assuntos
MicroRNAs , RNA Circular , Animais , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , MicroRNAs/genética , Desenvolvimento Muscular , Músculos , Suínos/genética
11.
DNA Cell Biol ; 40(11): 1369-1380, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34767731

RESUMO

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, but the molecular mechanisms of disease remain not very clear and there is no curative therapeutic strategy so far. This study was carried out to identify the expression profile of circular RNA (circRNA) in human DKD and explore circRNA regulatory function in glomeruli and tubuli simultaneously. As a result, a total of 40 upregulated and 23 downregulated differentially expressed circRNAs (DEcircRNAs) were detected. Six candidate DEcircRNAs were verified by quantitative real-time polymerase chain reaction in high glucose-treated human mesangial cells and human proximal renal tubular epithelial cells, respectively. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that both in glomeruli and in tubuli the DEcircRNAs-targeted genes participated in many pathophysiological processes of DKD. Correlation analysis with renal function showed that expression level of DEcircRNA-targeted hub gene was related to renal function. In conclusion, this is the first study to report expression profiles of circRNAs in kidney of DKD patients, and further analysis demonstrated that circRNA probably played a significant regulatory role, providing help for understanding the pathogenesis of DKD and investigating novel diagnostic and therapeutic strategy.


Assuntos
Nefropatias Diabéticas/genética , RNA Circular/genética , RNA Circular/fisiologia , China , Biologia Computacional/métodos , Diabetes Mellitus/genética , Nefropatias Diabéticas/fisiopatologia , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes , Humanos , Rim/metabolismo , Glomérulos Renais/metabolismo , Glomérulos Renais/fisiologia , Túbulos Renais/metabolismo , Túbulos Renais/fisiologia , MicroRNAs/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transcriptoma/genética
12.
World J Surg Oncol ; 19(1): 335, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34839824

RESUMO

BACKGROUND: Accumulating evidence demonstrated that circular RNAs (circRNAs) play pivotal regulatory roles in the pathology of cancers. Disclosing the roles and molecular mechanisms of circRNAs in tumorigenesis and development is essential to identify novel diagnostic and therapeutic targets. In this study, we explored the role of circVAPA in non-small-cell lung cancer (NSCLC) progression and its associated mechanism. METHODS: The expression level of RNA was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was assessed by MTT assay and colony-forming assay. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were assessed by transwell assays. Dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays were used to test the intermolecular interactions. The role of circVAPA was assessed in vivo. And xenograft tumor tissues were analyzed by immunohistochemistry (IHC) staining. RESULTS: CircVAPA expression was upregulated in NSCLC tissues and cell lines, and a high level of circVAPA was associated with a poor prognosis of NSCLC patients. CircVAPA silencing suppressed the proliferation, migration, and invasion and induced the apoptosis of NSCLC cells. CircVAPA served as a molecular sponge for microRNA-342-3p (miR-342-3p). miR-342-3p interference largely reversed circVAPA knockdown-mediated anti-tumor effects in NSCLC cells. Zinc finger E-box-binding homeobox 2 (ZEB2) was a target of miR-342-3p, and miR-342-3p overexpression suppressed the malignant behaviors of NSCLC cells largely by downregulating ZEB2. CircVAPA silence repressed xenograft tumor growth in vivo, and IHC assay confirmed that circVAPA silence restrained the proliferation and metastasis but induced the apoptosis of NSCLC cells in vivo. CONCLUSION: CircVAPA contributes to the progression of NSCLC by binding to miR-342-3p to upregulate ZEB2. CircVAPA/miR-342-3p/ZEB2 axis might be a novel potential target for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , MicroRNAs/genética , Prognóstico , RNA Circular , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética
13.
Cells ; 10(10)2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34685492

RESUMO

The ability of the ribonucleic acid (RNA) to self-replicate, combined with a unique cocktail of chemical properties, suggested the existence of an RNA world at the origin of life. Nowadays, this hypothesis is supported by innovative high-throughput and biochemical approaches, which definitively revealed the essential contribution of RNA-mediated mechanisms to the regulation of fundamental processes of life. With the recent development of SARS-CoV-2 mRNA-based vaccines, the potential of RNA as a therapeutic tool has received public attention. Due to its intrinsic single-stranded nature and the ease with which it is synthesized in vitro, RNA indeed represents the most suitable tool for the development of drugs encompassing every type of human pathology. The maximum effectiveness and biochemical versatility is achieved in the guise of non-coding RNAs (ncRNAs), which are emerging as multifaceted regulators of tissue specification and homeostasis. Here, we report examples of coding and ncRNAs involved in muscle regeneration and discuss their potential as therapeutic tools. Small ncRNAs, such as miRNA and siRNA, have been successfully applied in the treatment of several diseases. The use of longer molecules, such as lncRNA and circRNA, is less advanced. However, based on the peculiar properties discussed below, they represent an innovative pool of RNA biomarkers and possible targets of clinical value.


Assuntos
MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , RNA Mensageiro/metabolismo , RNA não Traduzido/genética , Regeneração , Animais , Biomarcadores/metabolismo , COVID-19 , Homeostase , Humanos , Camundongos , Músculo Esquelético/virologia , Miocárdio/metabolismo , Origem da Vida , RNA Circular , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Pequeno RNA não Traduzido/genética , RNA Viral/metabolismo , SARS-CoV-2/genética
14.
Medicine (Baltimore) ; 100(39): e27404, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596168

RESUMO

ABSTRACT: Cervical cancer (CC) is the third most common cancer among women and has a high mortality rate at the advanced stage. The mechanisms underlying the development and progression of CC are still elusive. Circular RNAs (circRNAs) play an important role in various physiological and pathological processes. The aim of this study was to identify the circRNAs significantly associated with cervical squamous cell carcinoma (CSCC), in order to discover novel diagnostic markers and elucidate their mechanistic basis.The circRNA expression profiles of CSCC and paired para-cancerous cervical tissues was downloaded from the Gene Expression Omnibus. Bioinformatics analysis were used to screen for the differentially expressed circRNAs (DECRs). The expression levels of hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0075341, hsa_circ_0007905, hsa_circ_0031027, hsa_circ_0065898, hsa_circ_0070190, and hsa_circ_0078383 were verified in CC and normal cervical tissues by quantitative real-time PCR.A total of 197 DECRs were identified between the CSCC and normal tissues, including 87 upregulated and 110 downregulated circRNAs. In addition, 37 miRNAs were predicted for the upregulated circRNAs and 39 for the downregulated circRNAs. Functional analysis showed that the DECRs were associated with positive regulation of substrate adhesion-dependent cell spreading, metabolism, positive regulation of GTPase activity, protein regulation, and intercellular adhesion. The MAPK signaling pathway that plays a significant role in the progression of CC, was also enriched. Consistent with the in-silico analysis, hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0007905 were upregulated and hsa_circ_0078383 was downregulated in CC tissues (P < .001), whereas hsa_circ_0075341 (P < .001) and hsa_circ_0031027 (P = .001) showed opposite trends.We identified novel diagnostic and therapeutic biomarkers of CSCC along with the mechanistic basis.


Assuntos
Carcinoma de Células Escamosas/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Neoplasias do Colo do Útero/genética , Biomarcadores/metabolismo , Regulação para Baixo , Feminino , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
15.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638635

RESUMO

Circular RNAs (circRNAs) are covalently closed RNA molecules generated by the back-splicing of exons from linear precursor mRNAs. Though various linear RNAs have been shown to play important regulatory roles in many biological and developmental processes, little is known about the role of their circular counterparts. In this study, we performed high-throughput RNA sequencing to delineate the expression profile and potential function of circRNAs during the five stages of pollen development in Brassica rapa. A total of 1180 circRNAs were detected in pollen development, of which 367 showed stage-specific expression patterns. Functional enrichment and metabolic pathway analysis showed that the parent genes of circRNAs were mainly involved in pollen-related molecular and biological processes such as mitotic and meiotic cell division, DNA processes, protein synthesis, protein modification, and polysaccharide biosynthesis. Moreover, by predicting the circRNA-miRNA network from our differentially expressed circRNAs, we found 88 circRNAs with potential miRNA binding sites, suggesting their role in post-transcriptional regulation of the genes. Finally, we confirmed the back-splicing sites of nine selected circRNAs using divergent primers and Sanger sequencing. Our study presents the systematic analysis of circular RNAs during pollen development and forms the basis of future studies for unlocking complex gene regulatory networks underpinning reproduction in flowering plants.


Assuntos
Brassica rapa/genética , Regulação da Expressão Gênica/genética , Pólen/genética , RNA Circular/genética , RNA de Plantas/genética , Sítios de Ligação/genética , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , MicroRNAs/genética , Splicing de RNA/genética , RNA Mensageiro/genética
16.
Chin Med J (Engl) ; 134(21): 2573-2582, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34670246

RESUMO

BACKGROUND: Circular RNA (circRNA) is a type of closed circular noncoding RNA (ncRNA), mostly formed by back-splicing or alternative splicing of pre-messenger RNA (mRNA). The aim of this study was to explore the expression profile of circRNA in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and discover potential molecular markers of AS. METHODS: The circRNA microarray technology was used to detect the expression of circRNAs in the peripheral blood of 6 patients with AS and 6 healthy controls (HC). To screen the differentially expressed circRNAs by fold change (FC) and P value, these differentially expressed circRNAs were analyzed by bioinformatics. In 60 cases of AS and 30 cases of HC, 4 circRNAs were subjected to real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and their correlation with various clinical indicators was analyzed. Finally, the receiver operating characteristic (ROC) curve was used to analyze their potential as AS diagnostic markers. RESULTS: The microarray results showed that there were 1369 significantly differently expressed (P < 0.05, FC > 1.5) circRNAs between the AS and HC groups (675 upregulated and 694 downregulated). The results of bioinformatics analysis suggested that they were mainly involved in "enzyme binding," "adenosine ribonucleotide binding," "MAPK signaling pathway", etc. The RT-qPCR results showed that the expressions of hsa_circRNA_001544 (U = 486.5, P < 0.05) and hsa_circRNA_102532 (U = 645, P < 0.05) were significantly different between the AS group and the HC group. The AS group was further divided into two subgroups: active AS (ASA) and stable AS (ASS). After analysis, it was found that compared with the HC group, hsa_circRNA_001544 was significantly increased in both ASA (U = 214, P < 0.05) and ASS groups (U = 273, P < 0.05), while hsa_circRNA_008961 (U = 250, P < 0.05) and hsa_circRNA_102532 (U = 295, P < 0.05) were only significantly increased in the ASA group. Furthermore, hsa_circRNA_012732 was significantly different between the ASA and ASS groups (U = 194, P < 0.05), and there was no statistical significance among the remaining groups. Correlation analysis results showed that hsa_circRNA_012732 was negatively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), high-sensitivity C-reactive protein (hsCRP), and globulin (GLOB) and positively correlated with lymphocyte count (LY), mean corpusular volume, and albumin (ALB), and hsa_circRNA_008961 was negatively correlated with platelet (PLT) count. ROC curve analysis showed that hsa_circRNA_001544 (95% CI = 0.610-0.831, P < 0.05) and hsa_circRNA_102532 (95% CI = 0.521-0.762, P < 0.05) were statistically significant, and their area under curve (AUC) values were 0.720 and 0.642, respectively. CONCLUSIONS: There are differentially expressed circRNAs in PBMCs of AS patients, and they may be involved in the occurrence and development of AS. Among these differentially expressed circRNAs, hsa_circRNA_012732 has the potential to become an indicator of disease activity, and hsa_circRNA_001544 has the potential to become a molecular marker for AS diagnosis.


Assuntos
RNA Circular , Espondilite Anquilosante , Humanos , Leucócitos Mononucleares , RNA/genética , Curva ROC , Espondilite Anquilosante/genética
17.
J Transl Med ; 19(1): 412, 2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600555

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have attracted increasing attention in recent years for their potential application as disease biomarkers due to their high abundance and stability. In this study, we attempted to screen circRNAs that can be used to predict postoperative recurrence and survival in patients with gastric cancer (GC). METHODS: High-throughput RNA sequencing was used to identify differentially expressed circRNAs in GC patients with different prognoses. The expression level of circRNAs in the training set (n = 136) and validation set (n = 167) was detected by quantitative real-time PCR (qRT-PCR). Kaplan-Meier estimator, receiver operating characteristic (ROC) curve and cox regression analysis were used to evaluate the prognostic value of circRNAs on recurrence-free survival (RFS) and overall survival (OS) in GC patients. CeRNA network prediction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the circRNAs with prognostic significance. RESULTS: A total of 259 differentially expressed circRNAs were identified in GC patients with different RFS. We found two circRNAs (hsa_circ_0005092 and hsa_circ_0002647) that highly expressed in GC patients with good prognoses, and subsequently established a predictive model for postoperative recurrence and prognosis evaluation, named circPanel. Patients with circPanellow might have shorter recurrence-free survival (RFS) and overall survival (OS). We also performed circRNA-miRNA-mRNA network prediction and functional analysis for hsa_circ_0005092 and hsa_circ_0002647. CONCLUSIONS: CircPanel has the potential to be a prognostic biomarker in GC patients with greater accuracy than a single circRNA and certain traditional tumor markers (e.g., CEA, CA19-9 and CA724).


Assuntos
RNA Circular , Neoplasias Gástricas , Biomarcadores Tumorais/genética , Humanos , Recidiva Local de Neoplasia/genética , Prognóstico , RNA/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética
18.
BMC Cancer ; 21(1): 1085, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620126

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are implicated in the development of oral squamous cell carcinoma (OSCC). The aim of current research is to elucidate the role and mechanism of circ_0011946 in the functional behaviors of OSCC cells. METHODS: Circ_0011946, microRNA (miR)-216a-5p, B cell lymphoma-2-like 2 protein (BCL2L2) abundances were exposed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation, migration, invasion and apoptosis were detected by MTT, colony formation assay, transwell, wound-healing and flow cytometry assays, respectively. Target correlation was tested by dual-luciferase reporter and RNA pull-down assays. An in vivo xenograft experiment was employed to investigate the function of circ_0011946 on tumor growth in vivo. RESULTS: Circ_0011946 and BCL2L2 levels were increased, while miR-216a-5p level was decreased in OSCC tissues and cells. Circ_0011946 knockdown impeded proliferation, migration, and invasion, but promoted apoptosis in OSCC cells. Circ_0011946 functioned as a sponge for miR-216a-5p, and BCL2L2 was targeted by miR-216a-5p. Besides, miR-216a-5p or BCL2L2 knockdown partly attenuated the inhibitory influences of circ_0011946 silence or miR-216a-5p overexpression on OSCC cell progression. Furthermore, circ_0011946 post-transcriptionally regulated BCL2L2 through sponging miR-216a-5p. Moreover, circ_0011946 knockdown constrained OSCC tumor growth in vivo. CONCLUSION: Circ_0011946 silence repressed OSCC cell proliferation, migration, and invasion, but promoted apoptosis through the regulation of the miR-216a-5p/BCL2L2 axis.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma de Células Escamosas/metabolismo , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , RNA Circular/metabolismo , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Inativação Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade Neoplásica/genética , Transplante de Neoplasias , Interferência de RNA
19.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638805

RESUMO

Tumors of the parathyroid glands are common endocrine diseases almost always characterized by parathyroid hormone hypersecretion that determines the clinical manifestations of primary hyperparathyroidism, such as fatigue, kidney problems, weakness, brittle bones, and other symptoms. Most parathyroid neoplasia are benign adenomas, although rare malignant forms have been described. They are heterogeneous in terms of clinical presentation and the associated signs and symptoms overlap with those of disease and aging. Furthermore, most patients with hypercalcemia are discovered during routine blood tests for other reasons. Surgical removal is considered the main therapeutic option to cure these endocrine tumors and, therefore, innovative therapeutic approaches are actively required. Recently, a growing number of studies have suggested that alterations to the epigenetic mechanisms could play a pivotal role in parathyroid tumorigenesis. Most of the attention has been focused on non-coding RNAs (ncRNAs) (i.e., miRNAs, lncRNAs, and circRNAs) whose expression profile has been found to be deregulated in parathyroid tumors. The aim of the present paper is to give an insight into the ncRNAs involved in parathyroid tumorigenesis, which could be used in the future either as innovative diagnostic biomarkers or as therapeutic targets for the treatment of this endocrine neoplasia.


Assuntos
Neoplasias das Paratireoides/metabolismo , RNA não Traduzido/análise , Biomarcadores Tumorais/análise , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/genética , RNA Circular , RNA Longo não Codificante , RNA não Traduzido/metabolismo
20.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638965

RESUMO

Endometriosis is a chronic gynecologic disease that negatively affects the quality of life of many women. Unfortunately, endometriosis does not have a cure. The current medical treatments involve hormonal manipulation with unwanted side effects and high recurrence rates after stopping the medication. Sadly, a definitive diagnosis for endometriosis requires invasive surgical procedures, with the risk of complications, additional surgeries in the future, and a high rate of recurrence. Both improved therapies and noninvasive diagnostic tests are needed. The unique molecular features of endometriosis have been studied at the coding gene level. While the molecular components of endometriosis at the small RNA level have been studied extensively, other noncoding RNAs, such as long intergenic noncoding RNAs and the more recently discovered subset of long noncoding RNAs called circular RNAs, have been studied more limitedly. This review describes the molecular formation of long noncoding and the unique circumstances of the formation of circular long noncoding RNAs, their expression and function in endometriosis, and promising preclinical studies. Continued translational research on long noncoding RNAs, including the more stable circular long noncoding RNAs, may lead to improved therapeutic and diagnostic opportunities.


Assuntos
Endometriose/sangue , Endometriose/genética , Processamento Pós-Transcricional do RNA/genética , RNA Circular/sangue , RNA Circular/genética , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , Biomarcadores/sangue , Feminino , Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Qualidade de Vida , RNA Circular/biossíntese , RNA Longo não Codificante/biossíntese
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