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1.
Virol Sin ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31637632

RESUMO

Prototype foamy virus (PFV) is a unique retrovirus that infects animals and humans and does not cause clinical symptoms. Long noncoding RNAs (lncRNAs) are believed to exert multiple regulatory functions during viral infections. Previously, we utilized RNA sequencing (RNA-seq) to characterize and identify the lncRNA lnc-RP5-1086D14.3.1-1:1 (lnc-RP5), which is markedly decreased in PFV-infected cells. However, little is known about the function of lnc-RP5 during PFV infection. In this study, we identified lnc-RP5 as a regulator of the PFV transcriptional transactivator (Tas). Lnc-RP5 enhanced the activity of the PFV internal promoter (IP). The expression of PFV Tas was found to be promoted by lnc-RP5. Moreover, miR-129-5p was found to be involved in the lnc-RP5-mediated promotion of PFV IP activity, while the Notch1 protein suppressed the activity of PFV IP and the expression of Tas. Our results demonstrate that lnc-RP5 promotes the expression of PFV Tas through the miR-129-5p/Notch1/PFV IP axis. This work provides evidence that host lncRNAs can manipulate PFV replication by employing miRNAs and proteins during an early viral infection.

2.
Intervirology ; 62(3-4): 156-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430761

RESUMO

BACKGROUND: Prototype foamy virus (PFV) is a complex and unique retrovirus with the longest genome among the retroviruses and is used as a vector for gene therapies. The viral Tas protein transactivates the viral long terminal repeat promoter and is required for viral replication. We have utilized RNA sequencing to identify and characterize the long-noncoding RNA NONHSAG000101 (lnc-NONH), which markedly increases in PFV-infected cells. However, little is known about the function of lnc-NONH. OBJECTIVES: We aim to explore the role of lnc-NONH during PFV infection. METHODS: To assess the lnc-NONH role during PFV infection, the siRNAs were used to silence the lnc-NONH expression. The microRNA (miRNA) mimic and inhibitor were employed to explore the function of lnc-NONH-related miRNA miR-34c-5p. Quantitative real-time polymerase chain reaction assay and Western blotting were applied to measure the mRNA and protein levels of PFV transactivator Tas. Luciferase assay was used to determine the transcriptional activity of the PFV unique internal promoter (IP). RESULTS: lnc-NONH promotes the expression of PFV Tas and miR-34c-5p. The interaction between lnc-NONH and miR-34c-5p enhances the transcriptional activity of the PFV IP. CONCLUSIONS: In the current study, we report a novel mechanism for the lnc-NONH-mediated upregulation of Tas expression. Our findings contribute to the understanding of regulatory network of Tas expression and PFV replication.

3.
Am J Orthod Dentofacial Orthop ; 155(5): 642-649, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31053279

RESUMO

INTRODUCTION: The purpose of this study was to investigate the effect of systemic delivery of Substance P (SP) on experimental tooth movement. METHODS: Forty-eight adult Sprague-Dawley rats were randomly divided into 2 groups and their maxillary first molars were mesially moved with the use of closed-coil springs. The experiment group received systemic injection of SP and the control group received phosphate-buffered saline solution. Transportation distances of first molars were measured. Hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, and immunohistochemistry staining were performed to evaluate alveolar bone remodeling. Then the interferon (IFN) γ and tumor necrosis factor (TNF) α concentrations in peripheral blood and local periodontal tissue were measured. Finally, the effects of SP on bone marrow-derived stem cell (BMSC) proliferation and migration were tested in vitro. RESULTS: Systemic delivery of SP significantly increased the distance of tooth movement and stimulated both osteoclast and osteoblast activities. The concentrations of IFN-γ and TNF-α increased in peripheral blood at early phases of the experiment and decreased in periodontal tissue at late phases. In vitro, the proliferation and migration of BMSCs were promoted by SP. CONCLUSIONS: Systemic delivery of SP can accelerate orthodontic tooth movement and promote alveolar bone remodeling potentially through immunomodulation and mobilizing endogenous mesenchymal stem cells.


Assuntos
Processo Alveolar/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Substância P/farmacologia , Técnicas de Movimentação Dentária , Animais , Biomarcadores/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Interferon gama/metabolismo , Maxila , Dente Molar , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Coloração e Rotulagem , Fator de Necrose Tumoral alfa/metabolismo
4.
Mol Med Rep ; 17(2): 3123-3132, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29257231

RESUMO

High mobility group box protein 1 (HMGB1) is a versatile molecule that affects the immune system in various ways; however, its role in cancer immunity has not yet been completely elucidated. In the current study, bone marrow­derived dendritic cells from BALB/c mice and undifferentiated murine colon carcinoma CT26.WT cells were used as a cellular model to study the primary role of HMGB1 in colon cancer immunity. Annexin V and acridine orange/ethidium bromide staining was used to assess cellular apoptosis, Cell Counting kit 8 and lactate dehydrogenase assays were performed to evaluate cell viability and a monodansylcadaverine assay was used to detect autophagy. Western blot analysis was performed to detect the expression levels of proteins of interest. Endoplasmic reticulum (ER) stress and c­Jun N­terminal kinase phosphorylation were also investigated in CT26.WT cells exposed to dendritic cells. The present results demonstrated that the CT26.WT cells underwent apoptotic cell death following co­culturing with dendritic cells. However, pretreatment with HMGB1 resulted in a significant increase in viability of the CT26.WT cells exposed to dendritic cells. Furthermore, HMGB1 promoted ER stress­induced autophagy through the activation of JNK, which inhibited the apoptosis triggered by the dendritic cells, suggesting that HMGB1 has a role in immune evasion by colon cancer cells.


Assuntos
Apoptose , Autofagia , Células Dendríticas/metabolismo , Estresse do Retículo Endoplasmático , Proteína HMGB1/metabolismo , Animais , Antracenos/farmacologia , Células Cultivadas , Técnicas de Cocultura , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Células Dendríticas/citologia , Feminino , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteína Sequestossoma-1/metabolismo
5.
J Physiol Biochem ; 71(1): 155-64, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25616500

RESUMO

Cancer stem cells (CSCs), or cancer cells with stem cell properties, are a rare population of tumor bulk and are recognized to be responsible for cancer recurrence, drug resistance, and metastasis. However, the molecular mechanisms of how to regulate the differentiation and self-renewing of CSCs are poorly understood. Krüppel-like factors (KLFs) are essential DNA-binding transcriptional regulators with diverse functions in various cellular processes, including differentiation, proliferation, inflammation, migration, and pluripotency. Recent progress has highlighted the significance of KLFs in tumor progression and CSCs. The regulatory functions of KLFs in the development of cancer and CSCs have become a burgeoning area of intense research. In this review, we summarize the current understanding and progress of the transcriptional regulation of KLFs in CSCs and discuss the functional implications of targeting CSCs by KLFs for cancer therapeutics.


Assuntos
Fatores de Transcrição Kruppel-Like/fisiologia , Células-Tronco Neoplásicas/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/classificação , Fatores de Transcrição Kruppel-Like/metabolismo , Filogenia
6.
Biochem Biophys Res Commun ; 441(4): 856-61, 2013 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-24211204

RESUMO

Coxsackievirus A16 (CA16) infection, which is responsible for hand, foot and mouth disease (HFMD), has become a common health problem in Asia due to the prevalence of the virus. Thus, it is important to understand the pathogenesis of CA16 infection. Viruses that induce endoplasmic reticulum (ER) stress are confronted with the unfolded protein response (UPR), which may lead to apoptotic cell death and influence viral replication. In this study, we found that CA16 infection could induce apoptosis and ER stress in RD cells. Interestingly, apoptosis via the activation of caspase-3, -8 and -9 in the extrinsic or intrinsic apoptotic pathways in RD cells was inhibited by 4-phenyl butyric acid (4PBA), a chemical chaperone that reduces ER stress. These results suggest that CA16 infection leads to ER stress, which in turn results in prolonged ER stress-induced apoptosis. This study provides a new basis for understanding CA16 infection and host responses.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Enterovirus , Doença de Mão, Pé e Boca/patologia , Doença de Mão, Pé e Boca/virologia , Linhagem Celular Tumoral , Humanos
7.
Cell Biol Int ; 37(9): 888-91, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23576457

RESUMO

The cancer stem cell (CSC) concept, which arose about a decade ago, proposes that tumor growth is sustained by a subpopulation of highly malignant cells. These cells, termed CSCs, are capable of extensive self-renewal that contributes to metastasis and treatment resistance. Therefore, therapeutic strategies that target CSCs should be developed for improving outcomes of cancer patients. Recent progress has highlighted the importance of physical properties of the extracellular matrix and mechanotransduction pathway in cancer cells during cancer development. On the other hand, the significance of CXCR1, an upstream signal of FAK/PI3K/Akt has been revealed in CSCs. FAK/PI3K/Akt is a key signal mediator in mechanotransduction pathway. Therefore, mechanotransduction could be a new target for CSCs, and would be an innovative way to treat cancer by inhibiting FAK/PI3K/Akt.


Assuntos
Regulação Neoplásica da Expressão Gênica , Mecanotransdução Celular , Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Receptores de Interleucina-8A/genética , Proliferação de Células , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Humanos , Neoplasias/genética , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Interleucina-8A/metabolismo
8.
Arch Immunol Ther Exp (Warsz) ; 61(3): 237-44, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23456208

RESUMO

Chemokines, by virtue of their ability to recruit immune cells into allografts, play critical roles in acute transplantation rejection. CCR9 and its ligand, CCL25, is one of the key regulators of thymocyte migration and maturation in normal and inflammatory conditions. Moreover, several studies have revealed that high expression of CCR9 and CCL25 participated in many kinds of diseases. However, the role of CCR9 in allograft rejection is still unclear. In this study, we established a murine skin transplantation model of acute rejection. Our findings showed that the proportion of CCR9-expressing T cells was significantly increased in the spleen of allotransplanted mice compared with syngeneic transplantation. Furthermore, expression of CCL25 in allograft was similarly increased. Neutralization of CCL25 by intravenous injection of anti-CCL25 monoclonal antibody significantly prolonged skin allograft survival, decreased the number of infiltrating cells, and simultaneously suppressed the chemotactic ability and the proliferation of the splenic T cells in response to allogeneic antigens. Finally, blockade of CCL25 also diminished the secretion of IFN-γ by splenic T cells. These studies indicated that CCR9/CCL25 was involved in acute transplantation rejection and anti-CCL25 strategies might be useful in preventing acute rejection.


Assuntos
Anticorpos Monoclonais/farmacologia , Quimiocinas CC/antagonistas & inibidores , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/farmacologia , Receptores CCR/imunologia , Transplante de Pele/imunologia , Pele/efeitos dos fármacos , Baço/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Doença Aguda , Animais , Anticorpos Monoclonais/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Quimiocinas CC/imunologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Rejeição de Enxerto/imunologia , Imunossupressores/administração & dosagem , Injeções Intravenosas , Interferon gama/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pele/imunologia , Transplante de Pele/efeitos adversos , Baço/imunologia , Linfócitos T/imunologia , Fatores de Tempo
9.
Clin Invest Med ; 35(3): E117-25, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22673314

RESUMO

PURPOSE: Paternally expressed gene 10 (PEG10) is important for apoptosis resistance in cancer cells; however, the effect of PEG10 on tumor cell migration remains poorly understood. In this study, we investigated the effects of PEG10 on proliferation, apoptosis, adhesion and migration in the Burkitt's lymphoma cell line, Raji. METHODS: Apoptosis was induced by 5-fluorouracil (5-FU) in pcDNA3.0/PEG10 transiently transfected HEK293T cells and PEG10-suppressed Raji cells. siRNAPEG10 was used to inhibit PEG10 expression. Fluorescence-activated cell sorting (FACS) were performed to analyze the effect of PEG10 on apoptosis. CCK-8 were performed to detect cell proliferation and adhesion. Matrigel invasion were performed using PEG10-suppressed Raji cells to investigate cell migration. The expression levels of matrix metalloproteinases -2and -9 (MMP-2 and MMP-9) were analyzed in PEG10-suppressed Raji cells using both real-time RT-PCR and Western blot analysis. RESULTS: HEK293T cells that overexpressed PEG10 exhibited greater viability 48 h following treatment with 5-FU, relative to control cells. Specific inhibition of PEG10 expression by siRNA resulted in inhibition of growth and apoptosis in Raji cells. Adherence and invasion capabilities were downregulated and expression levels of MMP-2 and MMP-9 were reduced in PEG10-suppressed Raji cells. CONCLUSIONS: Our findings demonstrated that PEG10 enhances the apoptotic resistance and viability of Raji cells. The migration and adherence invasion capacity of Raji cells could potentially be affected by regulation of the expression of MMP-2 and MMP-9. Our research provides a promising strategy for cancer immunotherapy of lymphoma.


Assuntos
Linfoma de Burkitt/enzimologia , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Proteínas/fisiologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Western Blotting , Linfoma de Burkitt/fisiopatologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Citometria de Fluxo , Fluoruracila/farmacologia , Células HEK293 , Humanos , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
10.
Cell Immunol ; 274(1-2): 98-108, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22361175

RESUMO

Lipopolysaccharide (LPS) plays an important role in the activation of innate immune cells, leading to secretion of proinflammatory factors and bridging the adaptive immune system. Exposing total mouse thymic cells culture to LPS induced a unique expression profile of cytokines (IL-17A, IL-17F, and IL-22) and the essential ROR-γt master transcription factor, which suggested a preferential differentiation of thymocytes towards the Th17 cell phenotype. Th17-polarizing molecules (IL-23, IL-23R, IL-6, and TGF-ß) and IL-17A(+)CD4(+) thymocytes were also specifically produced by the in vitro LPS-stimulation of thymic cells. Furthermore, both the expression of Th17 differentiation-related molecules and the frequency of Th17 cells were significantly up-regulated with increasing doses of LPS, as evidenced by quantitative RT-PCR and flow cytometric analysis, respectively. The expressions and frequency reached maximum levels when LPS exposure had been maintained at an extremely high concentration (100 µg/mL) for 48 h. On the other hand, depletion of thymic dendritic cells (DCs) blocked the LPS-induced polarization of thymus-derived Th17 cell lineage. Addition of bone marrow-derived DCs (BMDCs) to the purified immature CD4(+) CD62L(low) thymocytes culture recovered the switch towards Th17 cells, which synergistically prompted the cytotoxic activity of CD8(+) T cells. Taken together, our data indicates that high doses of LPS can promote the differentiation of mouse thymus-derived Th17 cells by a mechanism involving components associated with mature DCs.


Assuntos
Células Dendríticas/imunologia , Lipopolissacarídeos/imunologia , Ativação Linfocitária , Células Th17/imunologia , Timócitos/imunologia , Animais , Células da Medula Óssea/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Linhagem da Célula , Células Cultivadas , Técnicas de Cocultura , Feminino , Interleucina-17/biossíntese , Interleucina-23/biossíntese , Interleucina-6/biossíntese , Interleucinas/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/biossíntese , Timócitos/citologia , Fator de Crescimento Transformador beta/biossíntese
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