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1.
Ecotoxicol Environ Saf ; 188: 109901, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704323

RESUMO

Melon (Cucumis melo L.) is an important horticultural crop worldwide. Continuous cropping obstacle occurs in many melon cultivation area, resulting in poor plant growth and fruit quality, autotoxicity is the main reason for the obstacle. Silicon (Si) plays an important role in improving the resistance of plants to biotic and abiotic stresses. In this study, melon plant water extracts (MPWE) were used to simulate the autotoxicity stress. Different concentrations of Na2SiO3 (0, 1, 2, 4, 8, 16, 32 mM) were added into MPWE for preliminary concentration screening and alleviating effect determination of Si on melon seed autotoxicity. The results showed that autotoxicity reduced the seed germination index, inhibited the growth of germinated seeds. 2 mM Si significantly increased seed germination index and improved subsequent growth under autotoxicity. The effect of Si showed a concentration-dependent manner, which can be counteracted or even reversed at high concentration. Three treatment combinations, double distilled water, 0.02 g/mL MPWE and 2 mM Na2SiO3 + 0.02 g/mL MPWE were used for subsequent physiology, biochemistry and gene analysis. During the germination of melon seed under autotoxicity, starch degradation ability decreased, amylase activity and amylase gene expression were inhibited, cell membrane lipid peroxidation increased, and antioxidant enzyme activity was abnormal. In Si-addition group, the radicle growth, lateral roots number, starch degradation ability, amylase activity and amylase gene expression level increased. The addition of Si also maintained the activities of superoxide dismutase, catalase and peroxidase and the content of malondialdehyde in a relatively normal state. The change trend of amylase gene and antioxidant enzyme activity was complex, but the acute change coincided with the key stage of seed germination, which occurred when the seed was about to break through or just broken through the seed coat. Appropriate concentration of Si is an effective strategy to alleviate the autotoxicity on melon seed.

2.
Front Immunol ; 10: 2064, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543879

RESUMO

T cells recognize antigens as peptides bound to major histocompatibility complex (MHC) proteins through T cell receptors (TCRs) on their surface. To recognize a wide range of pathogens, each individual possesses a substantial number of TCRs with an extremely high degree of variability. It remains controversial whether germline-encoded TCR repertoire is shaped by MHC polymorphism and, if so, what is the preference between MHC genetic variants and TCR V gene compatibility. To investigate the "net" genetic association between MHC variations and TRBV genes, we applied quantitative trait locus (QTL) mapping to test the associations between MHC polymorphism and TCR ß chain V (TRBV) genes usage using umbilical cord blood (UCB) samples of 201 Chinese newborns. We found TRBV gene and MHC loci that are predisposed to interact with one another differ from previous conclusions. The majority of MHC amino acid residues associated with the TRBV gene usage show spatial proximities in known structures of TCR-pMHC complexes. These results show for the first time that MHC variants bias TRBV gene usage in UCB of Chinese ancestry and indicate that germline-encoded contacts influence TCR-MHC interactions in intact T cell repertoires.

4.
Bioinformatics ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31373607

RESUMO

MOTIVATION: T and B cell receptors (TCRs and BCRs) play a pivotal role in the adaptive immune system by recognizing an enormous variety of external and internal antigens. Understanding these receptors is critical for exploring the process of immunoreaction and exploiting potential applications in immunotherapy and antibody drug design. Although a large number of samples have had their TCR and BCR repertoires sequenced using high-throughput sequencing in recent years, very few databases have been constructed to store these kinds of data. To resolve this issue, we developed a database. RESULTS: We developed a database, the Pan Immune Repertoire Database (PIRD), located in China National GeneBank (CNGBdb), to collect and store annotated TCR and BCR sequencing data, including from Homo sapiens and other species. In addition to data storage, PIRD also provides functions of data visualisation and interactive online analysis. Additionally, a manually curated database of TCRs and BCRs targeting known antigens (TBAdb) was also deposited in PIRD. AVAILABILITY AND IMPLEMENTATION: PIRD can be freely accessed at https://db.cngb.org/pird.

5.
Food Chem ; 298: 125034, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31261013

RESUMO

A wash-free and label-free colorimetric biosensor for the amplified detection of aflatoxin B1 (AFB1) has been constructed by the integration of an ingenious hairpin DNA probe with exonuclease III (Exo III)-assisted signal amplification. The presence of the AFB1 activates the continuous cleavage reactions by Exo III toward a hairpin probe, resulting in the autonomous accumulation of numerous free G-quadruplex sequences, which can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce a colorimetric response. The naked-eye biosensor is ultrasensitive, enabling the visual detection of trace amounts of AFB1 as low as 1 pM without instrumentation. The sensor is robust and can work even when challenged with complex sample matrices such as peanut samples. With the advantages of simple operation, wash-free and label-free format, visible and intuitive output, and low cost, the naked-eye based colorimetric biosensor is expected to have potential applications for in-field detection of AFB1.


Assuntos
Aflatoxina B1/análise , Técnicas Biossensoriais/métodos , Colorimetria/métodos , Contaminação de Alimentos/análise , Benzidinas/química , Sondas de DNA/química , Exodesoxirribonucleases/química , Análise de Alimentos/métodos , Quadruplex G , Peróxido de Hidrogênio/química , Limite de Detecção
6.
Gut ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31300513

RESUMO

OBJECTIVE: SETD2, the sole histone H3K36 trimethyltransferase, is frequently mutated or deleted in human cancer, including pancreatic ductal adenocarcinoma (PDAC). However, whether SETD2/H3K36me3 alteration results in PDAC remains largely unknown. DESIGN: TCGA(PAAD) public database and PDAC tissue array with SETD2/H3K36me3 staining were used to investigate the clinical relevance of SETD2 in PDAC. Furthermore, to define the role of SETD2 in the carcinogenesis of PDAC, we crossed conditional Setd2 knockout mice (Pdx cre Setd2 flox/flox) together with Kras G12D mice. Moreover, to examine the role of SETD2 after ductal metaplasia, Crisp/cas9 was used to deplete Setd2 in PDAC cells. RNA-seq and H3K36me3 ChIP-seq were performed to uncover the mechanism. RESULTS: SETD2 mutant/low expression was correlated with poor prognosis in patients with PDAC. Next, we found that Setd2 acted as a putative tumour suppressor in Kras-driven pancreatic carcinogenesis. Mechanistically, Setd2 loss in acinar cells facilitated Kras-induced acinar-to-ductal reprogramming, mainly through epigenetic dysregulation of Fbxw7. Moreover, Setd2 ablation in pancreatic cancer cells enhanced epithelia-mesenchymal transition (EMT) through impaired epigenetic regulation of Ctnna1. In addition, Setd2 deficiency led to sustained Akt activation via inherent extracellular matrix (ECM) production, which would favour their metastasis. CONCLUSION: Together, our findings highlight the function of SETD2 during pancreatic carcinogenesis, which would advance our understanding of epigenetic dysregulation in PDAC. Moreover, it may also pave the way for development of targeted, patients-tailored therapies for PDAC patients with SETD2 deficiency.

7.
Gigascience ; 8(5)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31049560

RESUMO

BACKGROUND: For both pediatric and adult patients, umbilical cord blood (UCB) transplant is a therapeutic option for a variety of hematologic diseases, such as blood cancers, myeloproliferative disorders, genetic diseases, and metabolic disorders. However, the level of cellular heterogeneity and diversity of nucleated cells in UCB has not yet been assessed in an unbiased and systemic fashion. In the present study, nucleated cells from UCB were subjected to single-cell RNA sequencing to simultaneously profile the gene expression signatures of thousands of cells, generating a rich resource for further functional studies. Here, we report the transcriptomes of 17,637 UCB cells, covering 12 major cell types, many of which can be further divided into distinct subpopulations. RESULTS: Pseudotemporal ordering of nucleated red blood cells identifies wave-like activation and suppression of transcription regulators, leading to a polarized cellular state, which may reflect nucleated red blood cell maturation. Progenitor cells in UCB also comprise 2 subpopulations with activation of divergent transcription programs, leading to specific cell fate commitment. Detailed profiling of cytotoxic cell populations unveiled granzymes B and K signatures in natural killer and natural killer T-cell types in UCB. CONCLUSIONS: Taken together, our data form a comprehensive single-cell transcriptomic landscape that reveals previously unrecognized cell types, pathways, and mechanisms of gene expression regulation. These data may contribute to the efficacy and outcome of UCB transplant, broadening the scope of research and clinical innovations.

8.
Ann Rheum Dis ; 78(8): 1070-1078, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31101603

RESUMO

OBJECTIVE: T cell receptor (TCR) diversity determines the autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is closely associated with autoimmune diseases prognosis and prevention. However, the characteristics of variations in TCR diversity and their clinical significance is still unknown. Large series of patients must be studied in order to elucidate the effects of these variations. METHODS: Peripheral blood from 877 SLE patients, 206 RA patients and 439 healthy controls (HC) were amplified for the TCR repertoire and sequenced using a high-throughput sequencer. We have developed a statistical model to identify disease-associated TCR clones and diagnose autoimmune diseases. RESULTS: Significant differences were identified in variable (V), joining (J) and V-J pairing between the SLE or RA and HC groups. These differences can be utilised to discriminate the three groups with perfect accuracy (V: area under receiver operating curve > 0.99). One hundred ninety-eight SLE-associated and 53 RA-associated TCRs were identified and used for diseases classification by cross validation with high specificity and sensitivity. Disease-associated clones showed common features and high similarity between both autoimmune diseases. SLE displayed higher TCR heterogeneity than RA with several organ specific properties. Furthermore, the association between clonal expansion and the concentration of disease-associated clones with disease severity were identified, and pathogen-related TCRs were enriched in both diseases. CONCLUSIONS: These characteristics of the TCR repertoire, particularly the disease-associated clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.

9.
J Immunol ; 202(5): 1612-1622, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30700589

RESUMO

The rhesus macaque is a valuable preclinical animal model to estimate vaccine effectiveness and is also important for understanding Ab maturation and B cell repertoire evolution responding to vaccination. However, incomplete mapping of rhesus Ig germline genes hinders the research efforts. To address this deficiency, we sequenced the BCR repertoires of 75 Indian rhesus macaques. Using a bioinformatic method that has been validated with BCR repertoire analysis of three human donors, we were able to infer rhesus variable (V) and joint (J) germline alleles. We identified a total of 122 V and 20 J germline alleles, of which 91 V and 13 J alleles were novel, with 40 V novel genes, of which 8 were located at a novel genomic region not, to our knowledge, previously recorded. The novelty of these newly identified alleles was supported by two observations. First, the 50 V and 5 J novel alleles were observed in the whole genome sequencing data of 10 rhesus macaques. Second, using alignment reference including the novel alleles, the mutation rate of the rearranged repertoires significantly declined in nine other irrelevant samples, and all our identified novel V and J alleles were 100%-identity mapped by rearranged repertoire data. These identified novel alleles, along with the previously reported alleles, provide an important reference for future investigations of rhesus immune repertoire evolution in response to vaccination or infection. In addition, the method outlined in our study offers a powerful foundation for the identification of novel Ig alleles in the future.


Assuntos
Alelos , Região de Junção de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Receptores de Antígenos de Linfócitos B/genética , Animais , Biologia Computacional , Humanos , Região de Junção de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/imunologia , Macaca mulatta , Receptores de Antígenos de Linfócitos B/imunologia
11.
J Autoimmun ; 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30385082

RESUMO

Immunoglobulin A Nephropathy (IgAN) is the most common glomerulonephritis worldwide. The pathologic hallmark of IgAN is immune complex deposited in glomerular mesangium, which induces inflammation and affects the kidney's normal functions. The exact pathogenesis of IgAN, however, remains obscure. Further, in current clinical practice, the diagnosis relies on needle biopsy of renal tissue. Therefore, a non-invasive method for diagnosis and prognosis surveillance of the disease is highly desirable. To this end, we investigated the T cell receptor beta chain (TCRB) and immunoglobulin heavy chain (IGH) repertoire in circulating lymphocytes and compared them with kidney infiltrating lymphocytes using immune repertoire high throughput sequencing. We found that some features of TCRB and IGH in renal tissues were remarkably different from that in the blood, including decreased repertoire diversity, increased IgA and IgG frequency, and more antigen-experienced B cells. The complementarity-determining region 3 (CDR3) length of circulating TCRB and IGH in IgAN patients was significantly shorter than that in healthy controls, which is the result of both VDJ rearrangement and clonal selection. The IgA1 frequency in the blood of IgAN patients is significantly higher than that in other Nephropathy (NIgAN) patients and healthy control. Importantly we identified a set of TCRB and IGH clones, which can be used to distinguish IgAN from NIgAN and healthy controls with high accuracy. These results indicated that the TCRB and IGH repertoire can potentially serve as non-invasive biomarkers for the diagnosis of IgAN. The characteristics of the kidney infiltrating and circulating lymphocytes repertoires shed light on IgAN detection, treatment and surveillance.

12.
Front Immunol ; 9: 2194, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319643

RESUMO

The exploitation of various human immunodeficiency virus type-1 (HIV-1) vaccines has posed great challenges for the researchers in precisely evaluating the vaccine-induced immune responses, however, the understanding of vaccination response suffers from the lack of unbiased characterization of the immune landscape. The rapid development of high throughput sequencing (HTS) makes it possible to scrutinize the extremely complicated immunological responses during vaccination. In the current study, three vaccines, namely N36, N51, and 5-Helix based on the HIV-1 gp41 pre-hairpin fusion intermediate were applied in rhesus macaques. We assessed the longitudinal vaccine responses using HTS, which delineated the evolutionary features of both T cell and B cell receptor repertoires with extreme diversities. Upon vaccination, we unexpectedly found significant discrepancies in the landscapes of T-cell and B-cell repertoires, together with the detection of significant class switching and the lineage expansion of the B cell receptor or immunoglobulin heavy chain (IGH) repertoire. The vaccine-induced expansions of lineages were further evaluated for mutation rate, lineage abundance, and lineage size features in their IGH repertoires. Collectively, these findings conclude that the N51 vaccine displayed superior performance in inducing the class-switch of B cell isotypes and promoting mutations of IgM B cells. In addition, the systematic HTS analysis of the immune repertoires demonstrates its wide applicability in enhancing the understanding of immunologic changes during pathogen challenge, and will guide the development, evaluation, and exploitation of new generation of diagnostic markers, immunotherapies, and vaccine strategies.

13.
Nat Commun ; 9(1): 1320, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29615621

RESUMO

Electrocatalytic carbon dioxide reduction to formate is desirable but challenging. Current attention is mostly focused on tin-based materials, which, unfortunately, often suffer from limited Faradaic efficiency. The potential of bismuth in carbon dioxide reduction has been suggested but remained understudied. Here, we report that ultrathin bismuth nanosheets are prepared from the in situ topotactic transformation of bismuth oxyiodide nanosheets. They process single crystallinity and enlarged surface areas. Such an advantageous nanostructure affords the material with excellent electrocatalytic performance for carbon dioxide reduction to formate. High selectivity (~100%) and large current density are measured over a broad potential, as well as excellent durability for >10 h. Its selectivity for formate is also understood by density functional theory calculations. In addition, bismuth nanosheets were coupled with an iridium-based oxygen evolution electrocatalyst to achieve efficient full-cell electrolysis. When powered by two AA-size alkaline batteries, the full cell exhibits impressive Faradaic efficiency and electricity-to-formate conversion efficiency.

14.
Sci Rep ; 8(1): 5438, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29615712

RESUMO

Sub-wavelength antireflection moth-eye structures were fabricated with Nickel mold using Roll-to-Plate (R2P) ultraviolet nanoimprint lithography (UV-NIL) on transparent polycarbonate (PC) substrates. Samples with well replicated patterns established an average reflection of 1.21% in the visible light range, 380 to 760 nm, at normal incidence. An excellent antireflection property of a wide range of incidence angles was shown with the average reflection below 4% at 50°. Compared with the unpatterned ultraviolet-curable resin coating, the resulting sub-wavelength moth-eye structure also exhibited increased hydrophobicity in addition to antireflection. This R2P method is especially suitable for large-area product preparation and the biomimetic moth-eye structure with multiple performances can be applied to optical devices such as display screens, solar cells, or light emitting diodes.

15.
Cancer Res ; 78(12): 3293-3305, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29572224

RESUMO

Chronic inflammation is a feature of pancreatic cancer, but little is known about how immune cells or immune cell-related signals affect pancreatic cancer stemness and development. Our previous work showed that IL22/IL22RA1 plays a vital role in acute and chronic pancreatitis progression by mediating cross-talk between immune cells and acinar cells or stellate cells, respectively. Here, we find IL22RA1 is highly but heterogeneously expressed in pancreatic cancer cells, with high expression associated with poor prognosis of patients with pancreatic cancer. The IL22RA1hi population from pancreatic cancer harbored higher stemness potential and tumorigenicity. Notably, IL22 promoted pancreatic cancer stemness via IL22RA1/STAT3 signaling, establishing the mechanism of regulation of cancer stemness by microenvironmental factors. Moreover, STAT3 was indispensable for the maintenance of IL22RA1hi cells. Overall, these findings provide a therapeutic strategy for patients with PDAC with high expression of IL22RA1.Significance: IL22RA1/STAT3 signaling enhances stemness and tumorigenicity in pancreatic cancer. Cancer Res; 78(12); 3293-305. ©2018 AACR.

16.
Biochem Biophys Res Commun ; 498(3): 551-558, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29522715

RESUMO

Hepatocellular carcinoma (HCC) contributes to cancer-related deaths greatly every year in the world. However, there is still no radical method for HCC treatment. Here we screened out a lncRNA FABP5P3 that was up-regulated in HCC tissues. Patients with higher FABP5P3 expression displayed poorer survival rate. FABP5P3 depletion in HCC cell lines and sample cells remarkably inhibited the abilities of proliferation, migration and invasion. In mechanism, we showed that FABP5P3 bond to miR-589-5p which served as a tumor suppressor. MiR-589-5p targeted directly the mRNA of ZMYND19 whose function has not been defined in HCC. FABP5P3 promoted HCC development and progression by sponging miR-589-5p and up-regulating ZMYND19 expression. In sum, we showed that FABP5P3/miR-589-5p/ZMYND19 axis regulates cell proliferation and migration in HCC, which may serve as a new target for HCC treatment.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , MicroRNAs/genética , Invasividade Neoplásica/genética , RNA Longo não Codificante/genética , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Humanos , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/patologia , Transdução de Sinais
17.
J Immunol ; 200(6): 2104-2114, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29440506

RESUMO

Acute pancreatitis (AP) is a sterile inflammation, in which inflammatory monocytes (CD11b+Ly-6Chi) are recruited into the inflamed tissue at the onset of disease. Monocyte infiltration and activation at the site of inflammation are critical to the pathogenesis of AP. Our previous studies have shown a protective role for CO in AP, which is partially mediated by inhibition of macrophage activation via TLR4 signaling. In the current study, to gain a better understanding of CO's therapeutic effect, we further investigated whether CO could affect inflammatory monocyte trafficking during AP. In a mouse model of AP, we found that treatment with CO-releasing molecule-2 (CORM-2) impaired recruitment of inflammatory monocytes, but not that of neutrophils, from peripheral blood to inflamed pancreas. During the early stage of AP, a single dose of CORM-2 decreased pancreatic CCL2 and soluble ICAM-1 expression. In addition, using in vivo and in vitro experiments, we found that CORM-2 had the ability to inhibit CD11b+Ly-6Chi monocyte migration via blockade of CCR2 endocytosis. Notably, we showed that CORM-2 inhibited CCR2 endocytosis of inflammatory monocytes (CD14hiCD16-) from AP patients. Taken together, our results highlighted CO's effect on inflammatory monocyte trafficking, shedding additional light on its therapeutic potential in AP.

18.
ACS Appl Mater Interfaces ; 10(7): 6785-6792, 2018 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-29388421

RESUMO

Electrorheological (ER) fluids are considered as a type of smart fluids because their rheological characteristics can be altered through an electric field. The discovery of giant ER effect revived the researchers' interest in the ER technological area. However, the poor stability including the insufficient dynamic shear stress, the large leakage current density, and the sedimentation tendency still hinders their practical applications. Herein, we report a facile and scalable coprecipitation method for synthesizing surfactant-free tin titanyl oxalate (TTO) particles with tremella-like wrinkly microstructure (W-TTO). The W-TTO-based ER fluids exhibit enhanced ER activity compared to that of the pristine TTO because of the improved wettability between W-TTO and the silicone oil. In addition, the static yield stress and leakage current of W-TTO ER fluids also show a fine time stability during the 30 day tests. More importantly, the dynamic shear stress of W-TTO ER fluids can remain stable throughout the shear rate range, which is valuable for their use in engineering applications. The results in this work provided a promising strategy to solving the long-standing problem of ER fluid stability. Moreover, this convenient route of synthesis may be considered a green approach for the mass production of giant ER materials.

19.
ACS Nano ; 12(2): 1829-1836, 2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-29397688

RESUMO

Even though advocated as the potential low-cost alternatives to current lithium-ion technology, the practical viability of sodium-ion batteries remains illusive and depends on the development of high-performance electrode materials. Very few candidates available at present can simultaneously meet the requirements on capacity, rate capability, and cycle life. Herein, we report a high-temperature solution method to prepare Ni3S4 nanorods with uniform sizes. These colloidal nanorods readily self-assemble side by side and form microsized superstructures, which unfortunately negates the nanoscale feature of individual nanorods. To this end, we further introduce two-dimensional graphene nanosheets as the spacer to interrupt nanorod self-assembly. Resultant composite presents a marked advantage toward electrochemical storage of Na+ ions. We demonstrate that in half-cells it exhibits large reversible specific capacity in excess of 600 mAh/g, high rate capability with >300 mAh/g retained at 4 A/g, and great cycle life at different current rates. This anode material can also be combined with the NASICON-type Na3V2(PO4)3 cathode in full cells to enable large capacity and good cyclability.

20.
Biochem Biophys Res Commun ; 497(2): 626-632, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-29458020

RESUMO

Recently, increasing evidences demonstrate that circular RNAs (circRNAs) exert very important functions in the progression of human cancers. However, the functions and molecular mechanism of circ_0067934 in hepatocellular carcinoma (HCC) are largely unknown. In the present study, we found that the expression of circ_0067934 was significantly upregulated in HCC tissues and cell lines compared to adjacent normal tissues. Furthermore, we showed that circ_0067934 knockdown remarkably suppressed the proliferation, migration and invasion of Hep3B and HuH7 cells while inducing their apoptosis. In terms of mechanism, we found that circ_0067934 directly suppressed miR-1324, which targeted the 3'-UTR of FZD5 mRNA and subsequently downregulated the Wnt/ß-catenin signaling pathway in HCC. Through rescue experiments, we demonstrated that circ_0067934 enhanced the proliferation, migration and invasion of HCC cells by the inhibition of miR-1324 and concomitant activation of FZD5/Wnt/ß-catenin signaling pathway. In summary, the circ_0067934/miR-1324/FZD5/ß-catenin signaling axis might serve as a promising therapeutic target for HCC intervention.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Animais , Apoptose , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Receptores Frizzled/genética , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Via de Sinalização Wnt
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