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1.
Microb Pathog ; 138: 103816, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655218

RESUMO

Duckling short beak and dwarfism syndrome virus (SBDSV), a newly identified goose parvovirus, causes devastating disease in domestic waterfowl and considerable economic losses to Chinese waterfowl industry. The molecular pathogenesis of SBDSV infection, nature and dynamics of host immune responses against SBDSV infection remained elusive. In this study, we systematically explored the relative mRNA expression profiles of major innate immune-related genes in SBDSV infected duck embryo fibroblasts. We found that SBDSV infection effectively activated host innate immune responses and resulted in significant up-regulation of IFN-ß and several vital IFN-stimulated genes (ISGs). These up-regulation responses were mainly attributed to viral genomic DNA and dsRNA replication intermediates. Importantly, the expression of cGAS was significantly induced, whereas the expression of other DNA receptors including DDX41, STING, ZBP1, LSM14A and LRRFIP1 have no significant change. Furthermore, SBDSV infection also activates the up-regulation of TLR3 and inhibited the expression of TLR2 and TLR4; however, no effect was observed on the expression of TLR1, TLR5, TLR7, TLR15 and TLR21. Intriguingly, SBDSV infection significantly up-regulated the expression of RNA sensors such as MDA5 and LGP2, and resulted in a delayed but significant up-regulation of RIG-I gene. Taken together, these data indicate that host multiple sensors including DNA sensor (cGAS) and RNA sensors (TLR3, MDA5 and LGP2) are involved in recognizing a variety of different pathogen associated molecular patterns (PAMPs) including viral genomic ssDNA and dsRNA replication intermediates, which trigger an effective antiviral innate immune response.

2.
Microb Pathog ; 137: 103764, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31585153

RESUMO

Novel duck reovirus (NDRV) is pathogenic to young ducks, which is characterized by hemorrhagic spots and necrotic foci of the livers and necrotic foci of spleens. However, the effect of NDRV infection on the composition of the host's intestinal microbiota remains poorly understood. In this study, three-day-old Muscovy ducklings were inoculated with either the virulent NDRV strain NP03 or sterile Hank's solution. Through Illumina MiSeq sequencing, the whole cecal microbiota of healthy and NDRV infected ducklings was examined. The results showed that the gut microbiota was mainly dominated by Firmicutes, Proteobacteria and Bacteroidestes in both healthy and NDRV infected ducks. NDRV infection altered the relative abundance of bacteria. Specifically, families Ruminococcaceae and Lachnospiraceae were remarkably reduced, whereas Escherichia_Shigella belonging to family Enterobacteriaceae was significantly increased. Collectively, NDRV infection in Muscovy ducks resulted in a shift of the gut microbiota, including a net loss of probiotic bacteria with a compensatory expansion of pathogenic bacteria. These results provide new insights into the potential pathogenic mechanisms of NDRV.

3.
Mol Cell Probes ; 46: 101410, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128205

RESUMO

Muscovy duck-origin goose parvovirus (MDGPV) is a causative agent of MDGPV-associated Derzsy's disease. To evalute the role of the cis-acting element E-box (CACATG) deletion on MDGPV eplication, an infectious plasmid clone p-PTΔE287, having one E-box deletion at nucleotide (nt) 287 of the left inverted terminal repeat sequence (L-ITR), was constructed by overlap extension PCR deleting the 287CACATG292 motif from the plasmid pMDGPVPT containing the full-length genome of the virulent MDGPV strain PT. The p-PTΔE287 plasmid was transfected into 9-day-old non-immune Muscovy duck embryos via the yolk sac, resulting in successful rescue of the deletion mutant virus r-PTΔE287. Compared with its parental virus PT, the virulence and the replication ability of r-PTΔE287 were reduced. In addition, we examined the ability of r-PTΔE287 to manipulate cell cycle progression. The results showed that r-PTΔE287 replication results in G0/G1 phase accumulation of infected duck embryo liver mesenchymal stem cells (BMSCs) and that this accumulation is caused by the prevention of cell cycle entry from G0/G1 phase into S phase. Taken together, introducing 287CACATG292 element deletion into MDGPV PT genomic DNA that induced rescued mutant virus (r-PTΔE287) cell cycle arrest function at the G0/G1 phase, which might inhibit MDGPV replication and virus progeny production. This study laid the foundation for further understanding of the relationship between E-box deletion in the L-ITR and MDGPV virulence.

4.
Cell Biol Int ; 43(8): 863-874, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31033093

RESUMO

We had previously identified that the co-expression of transmembrane CXCL16 (TM-CXCL16) and its receptor CXCR6 is an independent risk factor for poor survival in patients with diffuse large B-cell lymphoma (DLBCL). However, the impact of the soluble form of CXCL16 (sCXCL16) on the pathogenesis of DLBCL remains unknown. In the present study, the synergistic effect of sCXCL16 and tumor necrosis factor α (TNF-α) on apoptosis in DLBCL cell lines (OCI-LY8 and OCI-LY10) was investigated in vitro. sCXCL16 reinforced TNF-α-mediated inhibition of DLBCL cell proliferation, as determined by the cell counting kit-8 assay. The results of annexin V staining showed that sCXCL16 enhanced TNF-α-induced apoptosis in OCI-LY8 and OCI-LY10 cells through a death receptor-caspase signaling pathway. The results of gene microarray suggested a significant upregulation of differentially expressed genes in the TNF signaling pathway. sCXCL16 increased the concentration of extracellular TNF-α by binding to CXCR6 to activate the nuclear factor-κB (NF-κB) signaling pathway. TNF-α also induced the secretion of sCXCL16 by increasing the expression of ADAM10, which is known to cleave TM-CXCL16 to yield sCXCL16. Moreover, bioinformatics analysis revealed that elevated TNF-α and ADAM10 expression levels in tumor tissues predicted better survival in patients with DLBCL. Thus, our study suggests that sCXCL16 enhances TNF-α-induced apoptosis of DLBCL cells, which may involve a positive feedback loop consisting of TNF-α, ADAM10, sCXCL16, and members of the NF-κB pathway. sCXCL16 and TNF-α may be used as prognostic markers in the clinic, and their combinational use is a promising approach in the context of DLBCL therapy.

6.
Virol J ; 16(1): 6, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630503

RESUMO

BACKGROUND: Waterfowl parvoviruses, including goose parvovirus (GPV) and Muscovy duck parvovirus (MDPV), can cause seriously diseases in geese and ducks. Developing a fast and precise diagnosis assay for these two parvoviruses is particularly important. RESULTS: A duplex SYBR Green I-based quantitative real-time PCR assay was developed for the simultaneous detection and differentiation of GPV and MDPV. The assay yielded melting curves with specific single peak (Tm = 87.3 ± 0.26 °C or Tm = 85.4 ± 0.23 °C) when GPV or MDPV was evaluated, respectively. When both parvoviruses were assessed in one reaction, melting curves with specific double peaks were yielded. CONCLUSION: This duplex quantitative RT-PCR can be used to rapid identify of GPV and MDPV in field cases and artificial trials, which make it a powerful tool for diagnosing, preventing and controlling waterfowl parvovirus infections.


Assuntos
Patos/virologia , Gansos/virologia , Infecções por Parvoviridae/veterinária , Parvovirus/classificação , Doenças das Aves Domésticas/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Animais , Cloaca/virologia , Genoma Viral , Compostos Orgânicos , Orofaringe/virologia , Infecções por Parvoviridae/diagnóstico , Parvovirus/isolamento & purificação , Filogenia , Doenças das Aves Domésticas/virologia , Temperatura de Transição , Carga Viral
7.
Vaccine ; 36(52): 8001-8007, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30420117

RESUMO

The Muscovy duck reovirus (MDRV) is a highly pathogenic virus that causes substantial economic losses in the Muscovy duck industry. While MDRV poses a significant threat to Muscovy ducklings, no vaccine candidates are available to date to alleviate MDRV infection throughout the world. The present study presents efforts toward establishing an attenuated vaccine for MDRV. For this purpose, a live attenuated vaccine strain named CA was obtained via alternate propagation of the MDRV isolate MW9710 in both Muscovy duck embryo fibroblasts (MDEFs) and chicken embryo fibroblasts (CEFs) for 90 passages. The CA strain achieved an adaptive growth capacity in CEFs with a viral titer that ranged between 105.0-105.5 TCID50/100 µL and lost its pathogenicity in 1-day-old Muscovy ducklings. Compared to the parent strain MW9710, the CA strain has 42 scattered amino acid substitutions, most of which are located in the λB, λC, µB, σB, and σC protein. The CA strain maintained its attenuation and showed no gene mutation or virulence reversion after back propagation into 1-day-old ducklings for five rounds. The minimum protective dose was calculated to be 300 TCID50 of the CA strain. Furthermore, a single dose of CA vaccine protected immunized ducklings against lethal challenge by the virulent MDRV strain MW9710 and significantly decreased viral loads. In summary, the CA strain exhibited striking genetic stability, excellent safety, and effective immunogenicity. This CA strain of MDRV is a promising vaccine candidate for the prevention and control of MDRV infection.

8.
Sci Rep ; 8(1): 14402, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30258071

RESUMO

TFPI-2 has been recognized as a potent tumor suppressor gene. Low expression of TFPI-2 results in enhanced growth and metastasis of a variety of human tumors. In the present study, we investigated the mechanism responsible for the tumor suppressive effect of TFPI-2. Overexpression of TFPI-2 decreased phosphorylation of ERK1/2 and the translocation of p-ERK1/2 from cytoplasm into the nucleus, and eventually resulted in a reduced cell proliferation. Immunoprecipitation assays identified myosin-9 and actinin-4 as TFPI-2-interacting proteins. Full-length TFPI-2 was required for binding to actinin-4, whereas the N + KD1 regions of TFPI-2 were sufficient to interact with myosin-9. Although overexpression of TFPI-2 or TFPI-2/N + KD1 does not affect the expression of actinin-4 and myosin-9, it inhibits the migration and invasion of human breast cancer cells. Our results suggest that TFPI-2 suppresses cancer cell proliferation and invasion partly through the regulation of the ERK1/2 signaling and through interactions with myosin-9 and actinin-4.

9.
Mol Cell Probes ; 42: 32-35, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30240819

RESUMO

To obtain a deletion mutant of Muscovy duck-origin goose parvovirus (MDGPV) and to analyze its biological characteristics, the pMDGPVPT plasmid, which contains a full-length DNA infectious clone of the MDGPV PT strain, was used in this study as the template. The E-box at nt 315 of the left inverted terminal repeat sequence (L-ITR) was deleted by overlap extension PCR to obtain the infectious recombinant plasmid p-PTΔE315. The p-PTΔE315 plasmid was transfected into 9-day-old non-immune Muscovy duck embryos via the yolk sac and the rescued deletion mutant virus r-PTΔE315 was generated. Experiments to demonstrate the novel deletion mutant virus' biological characteristics showed that r-PTΔE315 can cause typical lesions after infection of Muscovy duck embryos. Compared with its parent strain PT, the virulence of r-PTΔE315 and its proliferation ability in Muscovy duck embryos were attenuated, but its ability to replicate in MDEF cells was enhanced. This study laid the foundation for further understanding of the relationship between E-box deletion in the L-ITR and MDGPV virulence.

10.
J Clin Invest ; 128(7): 3071-3087, 2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-29889099

RESUMO

Ikaros/IKZF1 is an essential transcription factor expressed throughout hematopoiesis. IKZF1 is implicated in lymphocyte and myeloid differentiation and negative regulation of cell proliferation. In humans, somatic mutations in IKZF1 have been linked to the development of B cell acute lymphoblastic leukemia (ALL) in children and adults. Recently, heterozygous germline IKZF1 mutations have been identified in patients with a B cell immune deficiency mimicking common variable immunodeficiency. These mutations demonstrated incomplete penetrance and led to haploinsufficiency. Herein, we report 7 unrelated patients with a novel early-onset combined immunodeficiency associated with de novo germline IKZF1 heterozygous mutations affecting amino acid N159 located in the DNA-binding domain of IKZF1. Different bacterial and viral infections were diagnosed, but Pneumocystis jirovecii pneumonia was reported in all patients. One patient developed a T cell ALL. This immunodeficiency was characterized by innate and adaptive immune defects, including low numbers of B cells, neutrophils, eosinophils, and myeloid dendritic cells, as well as T cell and monocyte dysfunctions. Notably, most T cells exhibited a naive phenotype and were unable to evolve into effector memory cells. Functional studies indicated these mutations act as dominant negative. This defect expands the clinical spectrum of human IKZF1-associated diseases from somatic to germline, from haploinsufficient to dominant negative.

11.
Breast Cancer Res ; 20(1): 32, 2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-29669595

RESUMO

BACKGROUND: Long noncoding RNAs (LncRNAs) represent a class of widespread and diverse endogenous RNAs that can posttranscriptionally regulate gene expression through the interaction with RNA-binding proteins and micro RNAs (miRNAs). Here, we report that in breast carcinoma cells, the insulin-like growth factor 2 messenger RNA binding protein (IMP1) binds to lncRNA urethral carcinoma-associated 1 (UCA1) and suppresses the UCA1-induced invasive phenotype. METHODS: RT-qPCR and RNA sequence assays were used to investigate the expression of UCA1 and miRNAs in breast cancer cells in response to IMP1 expression. The role of IMP1-UCA1 interaction in cell invasion was demonstrated by transwell analysis through loss-of-function and gain-of-function effects. RNA pull-down and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular interactions of IMP1-UCA1 and UCA1-miR-122-5p involved in breast cancer cells. RESULTS: In breast cancer cells, IMP1 interacts with UCA1 via the "ACACCC" motifs within UCA1 and destabilizes UCA1 through the recruitment of CCR4-NOT1 deadenylase complex. Meanwhile, binding of IMP1 prevents the association of miR-122-5p with UCA1, thereby shifting the availability of miR-122-5p from UCA1 to the target mRNAs and reducing the UCA1-mediated cell invasion. Accordingly, either IMP1 silencing or UCA1 overexpression resulted in reduced levels of free miR-122-5p within the cytoplasm, affecting miR-122-5p in regulating its target mRNAs. CONCLUSIONS: Our study provides initial evidence that interaction between IMP1 and UCA1 enhances UCA1 decay and competes for miR-122-5p binding, leading to the liberation of miR-122-5p activity and the reduction of cell invasiveness.

12.
Sci Rep ; 7(1): 13575, 2017 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-29051606

RESUMO

TFPI-2 has recently been recognized as a tumor suppressor, which not only plays a fundamental role in modulation of ECM integrity, but also involves the regulation of many oncogenes. In this study, we investigated the potential mechanism of TFPI-2 in the suppression of breast cancer growth and invasion. We showed that, with either over-expression of TFPI-2 or after treatment with exogenous rTFPI-2, breast cancer cells exhibited reduced proliferation and invasion. We demonstrated that in addition to being secreted, TFPI-2 was also distributed throughout the cytoplasm and nucleus. Nuclear localization of TFPI-2 contributed to inhibition of MMP-2 mRNA expression, which could be reversed after the nuclear localization signal was deleted. In the nucleus, interaction of TFPI-2 with Ap-2α attenuated the binding of AP-2α to the MMP-2 promoter, therefore reducing the transcriptional activity of the gene. Our results suggest that one of the mechanisms by which TFPI-2 inhibits breast cancer cell invasion could be via the regulation of MMP-2 gene transcription.

13.
J Vet Med Sci ; 79(12): 2063-2069, 2017 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-29046506

RESUMO

Muscovy duck reovirus (MDRV) belongs to the Orthoreovirus genus of the Reoviridae family, which is a significant poultry pathogen leading to high morbidity and mortality in ducklings. However, the pathogenesis of the virus is not well understood. In the present study, two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE) combined with LC-MS-MS was used to identify differentially expressed proteins between Muscovy duck embryo fibroblasts (MDEF) infected with virulent (MV9710 strain) and attenuated (CA strain) MDRV and non-infected MDEFs. A total of 115 abundant protein spots were identified. Of these, 59 of differentially expressed proteins were detected, with functions in metabolism and utilization of carbohydrates and nucleotides, anti-stress, and regulation of immune and cellular process. GO analysis of the identified proteins showed that they belonged to the classes molecular function (141 proteins), cellular component (62 proteins), and biological process (146 proteins). The results were validated by qRT-PCR, which suggests that the analysis method of 2D PAGE combined with LC-MS-MS used in this study is reliable. This study lays a foundation for further investigation of the biology of MDRV infection in MDEF.


Assuntos
Orthoreovirus Aviário , Doenças das Aves Domésticas/virologia , Infecções por Reoviridae/veterinária , Animais , Patos/embriologia , Patos/virologia , Eletroforese em Gel Bidimensional/métodos , Eletroforese em Gel Bidimensional/veterinária , Embrião não Mamífero/metabolismo , Embrião não Mamífero/virologia , Fibroblastos/metabolismo , Fibroblastos/virologia , Regulação Viral da Expressão Gênica , Doenças das Aves Domésticas/embriologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/veterinária
14.
Vet Microbiol ; 203: 252-256, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28619152

RESUMO

Short beak and dwarfism syndrome virus (SBDSV) is a newly emerging distinct duck-origin goose parvovirus that belongs to the genus Dependovirus. Our previous studies have found that SBDSV was highly pathogenic to Cherry Valley ducklings and mule ducklings. However, little is known about its pathogenicity to other waterfowls. In the present study, the pathogenicity of SBDSV was evaluated in domesticated waterfowl including Muscovy ducklings, Sheldrake ducklings and domestic goslings. All experimentally infected birds exhibited remarkable growth retardation, anorexia and diarrhea similar to naturally infected birds. Interestingly, atrophic beaks and protruded tongues were not observed in all infection groups. At necropsies, no diagnostic pathological lesions were observed. Viral antigens existed in most organ tissues such as heart, liver, spleen, kidney, pancreas and intestine. All ducks in Muscovy duckling and Sheldrake duckling infected groups and 70% goslings in infected groups were seropositive for goose parvovirus (GPV) antibodies at 21dpi with the average titers as 28.4, 26.9, 24.0, respectively. Muscovy ducklings were more prominent in viral load and weight loss with a higher GPV antibodies titer than Sheldrake ducklings and goslings. Taken together, SBDSV exhibits a wide range of pathogenicity to main domesticated waterfowl with variable symptoms and cause considerable economic losses in China.


Assuntos
Doenças das Aves/virologia , Patos/virologia , Parvovirinae/patogenicidade , Animais , Anseriformes , Doenças das Aves/epidemiologia , Parvovirinae/isolamento & purificação , Carga Viral , Virulência
16.
Front Microbiol ; 8: 672, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28473814

RESUMO

Avian Tembusu virus (ATMUV) is a highly pathogenic flavivirus that causes significant economic losses to the Chinese poultry industry. Our previous experiments demonstrated that ATMUV infection effectively triggered host innate immune response through MDA5 and TLR3-dependent signaling pathways. However, little information is available on the role of interferon-stimulated genes (ISGs) in defending against ATMUV infection. In this study, we found that ATMUV infection induced robust expression of type I and type III interferon (IFNs) in duck tissues. Furthermore, we observed that expression of interferon-inducible transmembrane proteins (IFITMs) was significantly upregulated in DEF and DF-1 cells after infection with ATMUV. Similar results were obtained from in vivo studies using ATMUV-infected ducklings. Importantly, we showed that knockdown of endogenous IFITM1 or IFITM3 by specific shRNA markedly enhanced ATMUV replication in DF-1 cells. However, disruption of IFITM2 expression had no obvious effect on the ATMUV replication. In addition, overexpression of chicken or duck IFITM1 and IFITM3 in DF-1 cells impaired the replication of ATMUV. Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV infection can effectively restrict the virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV infection.

17.
Vet Res ; 47(1): 74, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27449021

RESUMO

Avian Tembusu virus (ATMUV) is a newly emerged flavivirus that belongs to the Ntaya virus group. ATMUV is a highly pathogenic virus causing significant economic loss to the Chinese poultry industry. However, little is known about the role of host innate immune mechanism in defending against ATMUV infection. In this study, we found that ATMUV infection significantly up-regulated the expression of type I and type III interferons (IFN) and some critical IFN-stimulated genes (ISG) in vivo and in vitro. This innate immune response was induced by genomic RNA of ATMUV. Furthermore, we observed that ATMUV infection triggered IFN response mainly through MDA5 and TLR3-dependent signaling pathways. Strikingly, shRNA-based disruption of IPS-1, IRF3 or IRF7 expression significantly reduced the production of IFN in the 293T cell model. Moreover, NF-κB was shown to be activated in both chicken and human cells during the ATMUV infection. Inhibition of NF-κB signaling also resulted in a clear decrease in expression of IFN. Importantly, experiments revealed that treatment with IFN significantly impaired ATMUV replication in the chicken cell. Consistently, type I IFN also exhibited promising antiviral activity against ATMUV replication in the human cell. Together, these data indicate that ATMUV infection triggers host innate immune response through MDA5 and TLR3-dependent signaling that controls IFN production, and thereby induces an effective antiviral immunity.


Assuntos
Infecções por Flavivirus/veterinária , Flavivirus/imunologia , Helicase IFIH1 Induzida por Interferon/fisiologia , Doenças das Aves Domésticas/virologia , Transdução de Sinais/imunologia , Receptor 3 Toll-Like/fisiologia , Animais , Embrião de Galinha/virologia , Galinhas/imunologia , Galinhas/virologia , Infecções por Flavivirus/imunologia , Infecções por Flavivirus/virologia , Imunidade Inata/imunologia , Interferons/fisiologia , Doenças das Aves Domésticas/imunologia , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária
18.
Arch Virol ; 161(9): 2407-16, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27314945

RESUMO

Many mule duck and Cherry Valley duck flocks in different duck-producing regions of China have shown signs of an apparently new disease designated "short beak and dwarfism syndrome" (SBDS) since 2015. The disease is characterized by dyspraxia, weight loss, a protruding tongue, and high morbidity and low mortality rates. In order to characterize the etiological agent, a virus designated SBDSV M15 was isolated from allantoic fluid of dead embryos following serial passage in duck embryos. This virus causes a cytopathic effect in duck embryo fibroblast (DEF) cells. Using monoclonal antibody diagnostic assays, the SBDSV M15 isolate was positive for the antigen of goose parvovirus but not Muscovy duck parvovirus. A 348-bp (2604-2951) VP1gene fragment was amplified, and its sequence indicated that the virus was most closely related to a Hungarian GPV strain that was also isolated from mule ducks with SBDS disease. A similar disease was reproduced by inoculating birds with SBDSV M15. Together, these data indicate that SBDSV M15 is a GPV-related parvovirus causing SBDS disease and that it is divergent from classical GPV isolates.


Assuntos
Bico/patologia , Patos , Nanismo/veterinária , Transmissão Vertical de Doença Infecciosa , Parvovirus/classificação , Doenças das Aves Domésticas/virologia , Animais , China/epidemiologia , Nanismo/virologia , Testes de Fixação do Látex , Microscopia Acústica , Parvovirus/genética , Parvovirus/patogenicidade , Parvovirus/ultraestrutura , Filogenia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/patologia , Testes Sorológicos/veterinária
20.
Oncotarget ; 7(13): 15690-702, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-26910917

RESUMO

We have previously reported the ability of IMP1 in inhibiting proliferation and invasiveness of breast carcinoma cells in vitro. In the current study, we utilized a mouse xenograft model to further investigate the function of IMP1 in breast tumor progression and its underlying mechanism. We demonstrated that IMP1 expression significantly suppressed the growth of MDA231 cell-derived xenograft tumors and subsequent lung metastasis. Microarray analyses and differential gene expression identified handful mRNAs, many of which were involved in breast tumor-growth and metastasis. Further studies revealed that these mRNAs were directly interacted with the KH34 domain of IMP1 and this interaction post-transcriptionally regulated their corresponding protein expression. Either deletion of the KH34 domain of IMP1 or alteration of the expression of IMP1-bound mRNAs affected cell proliferation and tumor growth, producing the same phenotypes as IMP1 knockdown. Correlation of increased IMP1 expression with the reduced levels of its bound mRNAs, such as PTGS2, GDF15 and IGF-2 transcripts, was also observed in human breast tumors. Our studies provide insights into a molecular mechanism that the positive function of IMP1 to inhibit breast tumor growth and metastasis could be through the regulation of its target mRNAs.


Assuntos
Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , RNA Mensageiro/biossíntese , Proteínas de Ligação a RNA/metabolismo , Animais , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Humanos , Camundongos , Camundongos SCID , Invasividade Neoplásica/patologia
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